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(a) Light micrograph of a wholemount view of amacrine cells in the cat retina stained with antibodies to tyrosine hydroxylase (Toh). Two cells are stained, together with their dendrites and the plexus of dendrites from neighbouring Toh cells. The meshwork of dendrites is very dense, runs in stratum 1 of the IP L and leaves only few holes for amacrine cells bodies and large dendrites to penetrate. Scale bar represents 100 pm. (b) Displaced 'starburst' amacrine cells of the rabbit retina are seen in wholemount view after staining with intracellular injection of the fluorescent dye, Lucifer yellow. There are about 250 ACh-b cell in this field (only 6 are stained by micro electrode staining). Each point in central retina like this, is overlapped by the dendritic trees of about 30 ACh-b cells. Scale bar represents 100 f.tm. From Vaney. 21
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Since amacrine cells are important interneurons of the inner retina and their activity may be detected in certain waveforms of the electroretinogram, this paper reviews their morphologies, classification, mosaics, neurotransmitter content, neural circuitry and physiological responses to light. Nine different amacrine cell types of cat, rabbit and h...
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... wide-field cells shown in wholemount draw ings in Fig. 4 are similar-looking at a superficial glance. On closer inspection, though, they are different in many regards. A18 has a widespread loose dendritic tree of very fine dendrites that are probably not fully impregnated by the Golgi stain used here. Its major dendrites run right under the amacrine cell bodies of the INL, in stratum 1 of the IPL. We consider A18 to be the dopaminergic amacrine cell of the mammalian retina. It is, of course, much more fully revealed in terms of its branching and dendritic plexus by the immunostain ing technique, where the whole population of these cells with their incredible overlapping dendritic trees is dramatically displayed (see Fig. 1a). Another feature of A18, which is only seen after dye injection 28 or immunostaining,2 9 is the presence of long axon-like processes running in different strata of the IPL, in the ganglion cell layer and sometimes into the outer plexiform layer ...
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... is an ON-centre rod pathway neuron that has a relatively simple wiring diagram (Fig. 12B). Its huge coverage of the IPL neuropil by its up to 1 mm dendritic spread, allows it to collect scotopic rod signals from several thousand rod bipolar axons. A17 is most commonly the other member of the dyad at which the All amacrine cell receives rod bipolar input. Like the All its ON-centre resQonse reflects the rod-generated ON-centre message?O But unlike the All, the A17 cell's only output is presently thought to be purely reciprocal synapses to the rod bipolar from which it receives input (Fig. 12B). 3 o It is exquisitely light sensitive and may play a role in converging rod signals from huge areas of retina and amplifying them at very low light intensities. Like the All and AS cells, A17 cell bodies and dendrites, as they pass through stratum 1 of the IPL, are synapsed upon by the dopaminergic amacrine cell processes (not shown in Fig. 12B but see Fig. 12D). Several other 'pale' and 'dark' appearing amacrine cell inputs also occur upon the A17 cell's dendrites in sublamina a of the IPL. 3o A17 is known to accumulate serotonin in rabbit retina 21 but is thought to be a GABA-ergic neuron in terms of neurotransmission, in all mam malian retinas. 4 ...
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... is an ON-centre rod pathway neuron that has a relatively simple wiring diagram (Fig. 12B). Its huge coverage of the IPL neuropil by its up to 1 mm dendritic spread, allows it to collect scotopic rod signals from several thousand rod bipolar axons. A17 is most commonly the other member of the dyad at which the All amacrine cell receives rod bipolar input. Like the All its ON-centre resQonse reflects the rod-generated ON-centre message?O But unlike the All, the A17 cell's only output is presently thought to be purely reciprocal synapses to the rod bipolar from which it receives input (Fig. 12B). 3 o It is exquisitely light sensitive and may play a role in converging rod signals from huge areas of retina and amplifying them at very low light intensities. Like the All and AS cells, A17 cell bodies and dendrites, as they pass through stratum 1 of the IPL, are synapsed upon by the dopaminergic amacrine cell processes (not shown in Fig. 12B but see Fig. 12D). Several other 'pale' and 'dark' appearing amacrine cell inputs also occur upon the A17 cell's dendrites in sublamina a of the IPL. 3o A17 is known to accumulate serotonin in rabbit retina 21 but is thought to be a GABA-ergic neuron in terms of neurotransmission, in all mam malian retinas. 4 ...
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... is an ON-centre rod pathway neuron that has a relatively simple wiring diagram (Fig. 12B). Its huge coverage of the IPL neuropil by its up to 1 mm dendritic spread, allows it to collect scotopic rod signals from several thousand rod bipolar axons. A17 is most commonly the other member of the dyad at which the All amacrine cell receives rod bipolar input. Like the All its ON-centre resQonse reflects the rod-generated ON-centre message?O But unlike the All, the A17 cell's only output is presently thought to be purely reciprocal synapses to the rod bipolar from which it receives input (Fig. 12B). 3 o It is exquisitely light sensitive and may play a role in converging rod signals from huge areas of retina and amplifying them at very low light intensities. Like the All and AS cells, A17 cell bodies and dendrites, as they pass through stratum 1 of the IPL, are synapsed upon by the dopaminergic amacrine cell processes (not shown in Fig. 12B but see Fig. 12D). Several other 'pale' and 'dark' appearing amacrine cell inputs also occur upon the A17 cell's dendrites in sublamina a of the IPL. 3o A17 is known to accumulate serotonin in rabbit retina 21 but is thought to be a GABA-ergic neuron in terms of neurotransmission, in all mam malian retinas. 4 ...
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... cells of cat retina are ON-OFF wide-field amacrine cells, often having cell bodies displaced to the ganglion cell layer, with their major dendritic stratification in strata 3 and 4 of the IPL. However, they have long axon-like processes that pass up into sublamina a. A22 cells show close morphological similarity to substance-P-immunoreactive (SP-IR) amacrine cells in the human retina and so we are proposing that they are equivalent cells. SP-IR amacrines are wide-field cells with large cell bodies (16!-Lm diameter) lying in normal or displaced positions on either side of the IPL. Their sturdy, spiny dendrites stratify predominantly in stratum 3 of the IPL and are postsynaptic with reciprocal synapses to putative OFF-centre cone bipolar cb6 cells (Fig. 12C). They also receive synapses from unidentified amacrine cells and other SP-IR cell dendrites. A22 cells are presynaptic to ganglion cell dendrites and directly to ganglion cell bodies (possibly some of the latter are of SP-IR ganglion cells). Axon-like processes pass from the dendritic plexus in stratum 3 to run in stratum 1 or stratum 5 and even down to the nerve fibre layer or up to the OPL. These axonal processes are presynaptic to amacrine and ganglion cells in stratum 5 and in stratum 1 to OFF-centre ganglion cells. They receive cone bipolar input from a putative cb7 type in stratum 1 of the IPL, and where their axon-like processes ascend to the OPL, they are also pre synaptic to cone bipolar cells of unknown type (Fig. 12C, shown for neatness to be presynaptic to cb7, but this is not proved yet). They are also concerned with innervating blood vessels in the nerve fibre layer (not shown). Almost certainly A22 cells, SP-IR amacrine cells of cat and human are GABA-ergic. 8 3 This ON OFF cell probably plays a similar role to the A19 and A23 cells in being recordable in the PNR and being involved in fast temporal aspects of the visual coding of the ganglion ...
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... cells of cat retina are ON-OFF wide-field amacrine cells, often having cell bodies displaced to the ganglion cell layer, with their major dendritic stratification in strata 3 and 4 of the IPL. However, they have long axon-like processes that pass up into sublamina a. A22 cells show close morphological similarity to substance-P-immunoreactive (SP-IR) amacrine cells in the human retina and so we are proposing that they are equivalent cells. SP-IR amacrines are wide-field cells with large cell bodies (16!-Lm diameter) lying in normal or displaced positions on either side of the IPL. Their sturdy, spiny dendrites stratify predominantly in stratum 3 of the IPL and are postsynaptic with reciprocal synapses to putative OFF-centre cone bipolar cb6 cells (Fig. 12C). They also receive synapses from unidentified amacrine cells and other SP-IR cell dendrites. A22 cells are presynaptic to ganglion cell dendrites and directly to ganglion cell bodies (possibly some of the latter are of SP-IR ganglion cells). Axon-like processes pass from the dendritic plexus in stratum 3 to run in stratum 1 or stratum 5 and even down to the nerve fibre layer or up to the OPL. These axonal processes are presynaptic to amacrine and ganglion cells in stratum 5 and in stratum 1 to OFF-centre ganglion cells. They receive cone bipolar input from a putative cb7 type in stratum 1 of the IPL, and where their axon-like processes ascend to the OPL, they are also pre synaptic to cone bipolar cells of unknown type (Fig. 12C, shown for neatness to be presynaptic to cb7, but this is not proved yet). They are also concerned with innervating blood vessels in the nerve fibre layer (not shown). Almost certainly A22 cells, SP-IR amacrine cells of cat and human are GABA-ergic. 8 3 This ON OFF cell probably plays a similar role to the A19 and A23 cells in being recordable in the PNR and being involved in fast temporal aspects of the visual coding of the ganglion ...
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... and immunostained ACh-containing starburst amacrine cells of the rabbit retina have been extensively studied at the electron microscope level by others.64,65 Cone bipolar and amacrine cell inputs are distributed irregularly over the entire dendritic tree but the proximal dendrites containing small spines are particularly choice for bipolar input. A small amount of All amacrine input may occur to the proximal dendrites of the ACh-a type cell. The varicosities borne on the distal ends of the dendrites (see Fig. 1 b) appear to be the only sites of synaptic output to ganglion cells. The postsynaptic ganglion cells for both ACh-a and ACh-b type cells are thought to be ON-OFF directional-selective bistrati fied ganglion cells? 1 , 22 ,65-6 9 Additionally, the mono stratified ON-directionally selective ganglion cell may be postsynaptic to the ACh-b type cel1. ...
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... dopaminergic amacrine cell provides a con siderable number of synapses to the All cell, either directly upon its cell body or upon its lobular appendages ( Fig. 10, upper; A, red arrowheads 62 , 78 ). As much as 51 % of the input to All amacrine cells is from various other amacrine cells and most of them occur in the central part of the cells' dendritic tree in strata 3-4? 9 What percentage of all these different amacrine cell inputs is from the dopaminergic amacrine cell is presently unknown. All amacrine cells are glycine-immunoreactive? 3 , 80 The All ama crine cells are the major carriers of rod signals to the ganglion cells in the retina. As such they may play a role in speeding up the slow potential rod messages for presentation to ganglion cells. In addition, because of their high density across all parts of the retina and their synaptic involvement with millions of rod bipolar cells, they may contribute in a major way to the pattern ...
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... wide-field amacrine cell (A1S), that is an ON centre cell in the turtle retina, makes most of its synaptic arrangements in stratum 1 of the IPL (Fig. 12D). Sparse cone bipolar input, putatively from cb7, occurs to the cell's primary dendrites in stratum ...
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... narrow-field bistratified rod amacrine cell, All, is primarily postsynaptic to rod bipolar axon ter minals in lower sublamina b of the IPL (30% of its inpue 9 ) (Fig. 10, upper) and is known to be an ON-centre neuron driven by its ON-centre rod bipolar input. Its major output is upon ganglion cells that have dendrites only in sublamina a, i.e. All cell lobular appendages synapse upon OFF-centre ex and 13 ganglion cells. 60 The All also passes rod-driven information through the ON-centre cb5 cone bipolar to ON-centre ex and 13 ganglion cells by means of gap junctions ( Fig. 10, upper; black spots on All primary dendrites to pink cb axon). A little OFF-centre cone bipolar input is provided to the All lobular appendages by cbl and cb2 OFF-centre cone bipolar cells in sublamina a (19% of input 79 ) (Fig. 10, yellow cb profiles). Thus, All cells do carry some cone pathway components to their ON-centre responses, which could come from excitatory input from ON-centre cb5 at the gap junctions, or from the direct cbl or cb2 synapses which would have to be inhibitory, in this case. All amacrine cells are also coupled across the retina in a weak electrical syncytium by virtue of the gap junctions between their arboreal dendrites in sublamina b ( Fig. 10, upper; gj, lower right). 8 , 24 , ...
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... narrow-field bistratified rod amacrine cell, All, is primarily postsynaptic to rod bipolar axon ter minals in lower sublamina b of the IPL (30% of its inpue 9 ) (Fig. 10, upper) and is known to be an ON-centre neuron driven by its ON-centre rod bipolar input. Its major output is upon ganglion cells that have dendrites only in sublamina a, i.e. All cell lobular appendages synapse upon OFF-centre ex and 13 ganglion cells. 60 The All also passes rod-driven information through the ON-centre cb5 cone bipolar to ON-centre ex and 13 ganglion cells by means of gap junctions ( Fig. 10, upper; black spots on All primary dendrites to pink cb axon). A little OFF-centre cone bipolar input is provided to the All lobular appendages by cbl and cb2 OFF-centre cone bipolar cells in sublamina a (19% of input 79 ) (Fig. 10, yellow cb profiles). Thus, All cells do carry some cone pathway components to their ON-centre responses, which could come from excitatory input from ON-centre cb5 at the gap junctions, or from the direct cbl or cb2 synapses which would have to be inhibitory, in this case. All amacrine cells are also coupled across the retina in a weak electrical syncytium by virtue of the gap junctions between their arboreal dendrites in sublamina b ( Fig. 10, upper; gj, lower right). 8 , 24 , ...
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... narrow-field bistratified rod amacrine cell, All, is primarily postsynaptic to rod bipolar axon ter minals in lower sublamina b of the IPL (30% of its inpue 9 ) (Fig. 10, upper) and is known to be an ON-centre neuron driven by its ON-centre rod bipolar input. Its major output is upon ganglion cells that have dendrites only in sublamina a, i.e. All cell lobular appendages synapse upon OFF-centre ex and 13 ganglion cells. 60 The All also passes rod-driven information through the ON-centre cb5 cone bipolar to ON-centre ex and 13 ganglion cells by means of gap junctions ( Fig. 10, upper; black spots on All primary dendrites to pink cb axon). A little OFF-centre cone bipolar input is provided to the All lobular appendages by cbl and cb2 OFF-centre cone bipolar cells in sublamina a (19% of input 79 ) (Fig. 10, yellow cb profiles). Thus, All cells do carry some cone pathway components to their ON-centre responses, which could come from excitatory input from ON-centre cb5 at the gap junctions, or from the direct cbl or cb2 synapses which would have to be inhibitory, in this case. All amacrine cells are also coupled across the retina in a weak electrical syncytium by virtue of the gap junctions between their arboreal dendrites in sublamina b ( Fig. 10, upper; gj, lower right). 8 , 24 , ...
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... narrow-field bistratified rod amacrine cell, All, is primarily postsynaptic to rod bipolar axon ter minals in lower sublamina b of the IPL (30% of its inpue 9 ) (Fig. 10, upper) and is known to be an ON-centre neuron driven by its ON-centre rod bipolar input. Its major output is upon ganglion cells that have dendrites only in sublamina a, i.e. All cell lobular appendages synapse upon OFF-centre ex and 13 ganglion cells. 60 The All also passes rod-driven information through the ON-centre cb5 cone bipolar to ON-centre ex and 13 ganglion cells by means of gap junctions ( Fig. 10, upper; black spots on All primary dendrites to pink cb axon). A little OFF-centre cone bipolar input is provided to the All lobular appendages by cbl and cb2 OFF-centre cone bipolar cells in sublamina a (19% of input 79 ) (Fig. 10, yellow cb profiles). Thus, All cells do carry some cone pathway components to their ON-centre responses, which could come from excitatory input from ON-centre cb5 at the gap junctions, or from the direct cbl or cb2 synapses which would have to be inhibitory, in this case. All amacrine cells are also coupled across the retina in a weak electrical syncytium by virtue of the gap junctions between their arboreal dendrites in sublamina b ( Fig. 10, upper; gj, lower right). 8 , 24 , ...
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... narrow-field bistratified amacrine cell of the cone system, A8, receives most of its bipolar input from OFF-centre cone bipolar axons of both sublamina a and b of the IPL. 6 3 Thus, in sublamina a, excitatory cone-driven signals come from cone bipolar cells like cb2 which we know are OFF-centre in physiology (Fig. 10, lower; yellow cb profile), and in sublamina b from cb6, another OFF-centre bipolar cell ( Fig. 10, lower; pink cb profile ). 81 Altogether cone bipolar synapses account for 42 % of the input to A8 cells. Lesser rod bipolar input (20%) also occurs to the lower dendrites in sublamina b of the IPL. As A8 is an OFF-centre physiological type, 6 3 the small ON-centre rod bipolar cell input is either masked or the input is through sign-inverting synapses at the synaptic ribbons of the rod bipolar. The A8 gives a rather transient OFF-response (Fig. 8) which could reflect the amacrine synapses (38% of input) occurring over all parts of its dendritic tree ( Fig. 10, lower; A, red ...
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... narrow-field bistratified amacrine cell of the cone system, A8, receives most of its bipolar input from OFF-centre cone bipolar axons of both sublamina a and b of the IPL. 6 3 Thus, in sublamina a, excitatory cone-driven signals come from cone bipolar cells like cb2 which we know are OFF-centre in physiology (Fig. 10, lower; yellow cb profile), and in sublamina b from cb6, another OFF-centre bipolar cell ( Fig. 10, lower; pink cb profile ). 81 Altogether cone bipolar synapses account for 42 % of the input to A8 cells. Lesser rod bipolar input (20%) also occurs to the lower dendrites in sublamina b of the IPL. As A8 is an OFF-centre physiological type, 6 3 the small ON-centre rod bipolar cell input is either masked or the input is through sign-inverting synapses at the synaptic ribbons of the rod bipolar. The A8 gives a rather transient OFF-response (Fig. 8) which could reflect the amacrine synapses (38% of input) occurring over all parts of its dendritic tree ( Fig. 10, lower; A, red ...
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... narrow-field bistratified amacrine cell of the cone system, A8, receives most of its bipolar input from OFF-centre cone bipolar axons of both sublamina a and b of the IPL. 6 3 Thus, in sublamina a, excitatory cone-driven signals come from cone bipolar cells like cb2 which we know are OFF-centre in physiology (Fig. 10, lower; yellow cb profile), and in sublamina b from cb6, another OFF-centre bipolar cell ( Fig. 10, lower; pink cb profile ). 81 Altogether cone bipolar synapses account for 42 % of the input to A8 cells. Lesser rod bipolar input (20%) also occurs to the lower dendrites in sublamina b of the IPL. As A8 is an OFF-centre physiological type, 6 3 the small ON-centre rod bipolar cell input is either masked or the input is through sign-inverting synapses at the synaptic ribbons of the rod bipolar. The A8 gives a rather transient OFF-response (Fig. 8) which could reflect the amacrine synapses (38% of input) occurring over all parts of its dendritic tree ( Fig. 10, lower; A, red ...
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... the cell body and primary dendrites in stratum 1 of the IPL also receive GABA-ergic and glyciner gic amacrine cell inputs. The major output of the A1S cell is in the fine network of dendrites around the cell bodies and apical dendrites of OFF-centre AS and ON-centre All cells (Fig. 12D). It is possible that glycinergic A4 amacrine cells80 also receive a few synapses from the Toh + dendrites. Cell bodies and fine dendrites in stratum 1 of ON centre A17 amacrine cells are also postsynaptic to dopamine cells?O Furthermore, GABA-ergic pro files, belonging to the interplexiform cell of cat retina, are postsynaptic to the dopamine cell axon like processes that run in the OPL (Fig. 12D, IPC), 62 while All amacrine arboreal dendrites in sublamina b, close to their synapses with rod bipolar cells, are also postsynaptic to dopamine cell axon-like pro cesses (Fig. 12D). Dopaminergic amacrine cells are thought to function in the circadian cycle of the shift from dark to light conditions, and in modulating the adaptational state of the whole ...
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... the cell body and primary dendrites in stratum 1 of the IPL also receive GABA-ergic and glyciner gic amacrine cell inputs. The major output of the A1S cell is in the fine network of dendrites around the cell bodies and apical dendrites of OFF-centre AS and ON-centre All cells (Fig. 12D). It is possible that glycinergic A4 amacrine cells80 also receive a few synapses from the Toh + dendrites. Cell bodies and fine dendrites in stratum 1 of ON centre A17 amacrine cells are also postsynaptic to dopamine cells?O Furthermore, GABA-ergic pro files, belonging to the interplexiform cell of cat retina, are postsynaptic to the dopamine cell axon like processes that run in the OPL (Fig. 12D, IPC), 62 while All amacrine arboreal dendrites in sublamina b, close to their synapses with rod bipolar cells, are also postsynaptic to dopamine cell axon-like pro cesses (Fig. 12D). Dopaminergic amacrine cells are thought to function in the circadian cycle of the shift from dark to light conditions, and in modulating the adaptational state of the whole ...
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... the cell body and primary dendrites in stratum 1 of the IPL also receive GABA-ergic and glyciner gic amacrine cell inputs. The major output of the A1S cell is in the fine network of dendrites around the cell bodies and apical dendrites of OFF-centre AS and ON-centre All cells (Fig. 12D). It is possible that glycinergic A4 amacrine cells80 also receive a few synapses from the Toh + dendrites. Cell bodies and fine dendrites in stratum 1 of ON centre A17 amacrine cells are also postsynaptic to dopamine cells?O Furthermore, GABA-ergic pro files, belonging to the interplexiform cell of cat retina, are postsynaptic to the dopamine cell axon like processes that run in the OPL (Fig. 12D, IPC), 62 while All amacrine arboreal dendrites in sublamina b, close to their synapses with rod bipolar cells, are also postsynaptic to dopamine cell axon-like pro cesses (Fig. 12D). Dopaminergic amacrine cells are thought to function in the circadian cycle of the shift from dark to light conditions, and in modulating the adaptational state of the whole ...
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... receives input from a few cb2 bipolar cells, and a few All amacrine cell lobular appendages in sublamina a of the IPL. However, the majority of the - a - b -input is from pale-appearing amacrine cells some of which could be OFF-centre A2 cells (Fig. 11, A23). The preponderance of amacrine inputs probably accounts for its transient physiology. A23's major output is to OFF-centre ganglion cell dendrites in sublamina a of the IPL, and in this respect may explain some of the latter type of ganglion cell's non linear response characteristics. 82 A23 appears to be immunoreactive for GABA. 61 A19 receives two types of cone bipolar input: the first is from OFF-centre cb2 cone bipolar cells of sublamina a, while the other is ON-centre input from cb5 at the sublamina alb border where cb5 passes into sublamina b. OFF-and ON-centre bipolar input could account for this cell's ON-OFF physiology. The predominant input is from amacrine cells of sub lamina a though. Some of the amacrine inputs could be from OFF-centre A2 cells while others are probably from other AI9 cells. Its output is reciprocal synapses to both types of bipolar, to unknown dark amacrines and possibly also to unknown ganglion cell profiles (Fig. 11, AI9). Gap junctions may connect AI9 dendrites one to another (Fig, 11, A19, gj). AI9 is GABA-ergic. 4 8 Both AI9 and A23 cells are probably involved in the transfer of fast messages from one area of retina to another. They may be the basis of the proximal negative response recordable in the intraretinal ERG and in the shift effect in Y type ganglion cells. bipolar axon terminals and dendrites of OFF-centre a and b ganglion cells (Fig. I2A). In some other reports it was erroneously named A4; 7 1 ,n however, its branching in strata 1 and 2 of sublamina a, rather than in strata 2 and 3, as does the otherwise similar appearing A4, causes us to rename this cell type as an A2. A2 cells receive bipolar input from OFF centre cbI and cb2 types of cone bipolar cell and make reciprocal synapses to the bipolar axons. The OFF-centre A2 amacrine cell response is then fed to OFF-centre ganglion cell dendrites. If the A2 cell makes inhibitory synapses upon ganglion cells, as is likely because it is thought to be a GABA-ergic cell type, 4 8 it might function in a dis inhibitory role to the centre response. Alternatively, A2 cells, despite being small-field types, might have a role in the generation of antagonistic surrounds of ganglion cells. 6 D A2 cells receive a great many amacrine inputs to their dendritic trees which could be from wider field cells than they are themselves. See text for detatled ...
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... receives input from a few cb2 bipolar cells, and a few All amacrine cell lobular appendages in sublamina a of the IPL. However, the majority of the - a - b -input is from pale-appearing amacrine cells some of which could be OFF-centre A2 cells (Fig. 11, A23). The preponderance of amacrine inputs probably accounts for its transient physiology. A23's major output is to OFF-centre ganglion cell dendrites in sublamina a of the IPL, and in this respect may explain some of the latter type of ganglion cell's non linear response characteristics. 82 A23 appears to be immunoreactive for GABA. 61 A19 receives two types of cone bipolar input: the first is from OFF-centre cb2 cone bipolar cells of sublamina a, while the other is ON-centre input from cb5 at the sublamina alb border where cb5 passes into sublamina b. OFF-and ON-centre bipolar input could account for this cell's ON-OFF physiology. The predominant input is from amacrine cells of sub lamina a though. Some of the amacrine inputs could be from OFF-centre A2 cells while others are probably from other AI9 cells. Its output is reciprocal synapses to both types of bipolar, to unknown dark amacrines and possibly also to unknown ganglion cell profiles (Fig. 11, AI9). Gap junctions may connect AI9 dendrites one to another (Fig, 11, A19, gj). AI9 is GABA-ergic. 4 8 Both AI9 and A23 cells are probably involved in the transfer of fast messages from one area of retina to another. They may be the basis of the proximal negative response recordable in the intraretinal ERG and in the shift effect in Y type ganglion cells. bipolar axon terminals and dendrites of OFF-centre a and b ganglion cells (Fig. I2A). In some other reports it was erroneously named A4; 7 1 ,n however, its branching in strata 1 and 2 of sublamina a, rather than in strata 2 and 3, as does the otherwise similar appearing A4, causes us to rename this cell type as an A2. A2 cells receive bipolar input from OFF centre cbI and cb2 types of cone bipolar cell and make reciprocal synapses to the bipolar axons. The OFF-centre A2 amacrine cell response is then fed to OFF-centre ganglion cell dendrites. If the A2 cell makes inhibitory synapses upon ganglion cells, as is likely because it is thought to be a GABA-ergic cell type, 4 8 it might function in a dis inhibitory role to the centre response. Alternatively, A2 cells, despite being small-field types, might have a role in the generation of antagonistic surrounds of ganglion cells. 6 D A2 cells receive a great many amacrine inputs to their dendritic trees which could be from wider field cells than they are themselves. See text for detatled ...
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... receives input from a few cb2 bipolar cells, and a few All amacrine cell lobular appendages in sublamina a of the IPL. However, the majority of the - a - b -input is from pale-appearing amacrine cells some of which could be OFF-centre A2 cells (Fig. 11, A23). The preponderance of amacrine inputs probably accounts for its transient physiology. A23's major output is to OFF-centre ganglion cell dendrites in sublamina a of the IPL, and in this respect may explain some of the latter type of ganglion cell's non linear response characteristics. 82 A23 appears to be immunoreactive for GABA. 61 A19 receives two types of cone bipolar input: the first is from OFF-centre cb2 cone bipolar cells of sublamina a, while the other is ON-centre input from cb5 at the sublamina alb border where cb5 passes into sublamina b. OFF-and ON-centre bipolar input could account for this cell's ON-OFF physiology. The predominant input is from amacrine cells of sub lamina a though. Some of the amacrine inputs could be from OFF-centre A2 cells while others are probably from other AI9 cells. Its output is reciprocal synapses to both types of bipolar, to unknown dark amacrines and possibly also to unknown ganglion cell profiles (Fig. 11, AI9). Gap junctions may connect AI9 dendrites one to another (Fig, 11, A19, gj). AI9 is GABA-ergic. 4 8 Both AI9 and A23 cells are probably involved in the transfer of fast messages from one area of retina to another. They may be the basis of the proximal negative response recordable in the intraretinal ERG and in the shift effect in Y type ganglion cells. bipolar axon terminals and dendrites of OFF-centre a and b ganglion cells (Fig. I2A). In some other reports it was erroneously named A4; 7 1 ,n however, its branching in strata 1 and 2 of sublamina a, rather than in strata 2 and 3, as does the otherwise similar appearing A4, causes us to rename this cell type as an A2. A2 cells receive bipolar input from OFF centre cbI and cb2 types of cone bipolar cell and make reciprocal synapses to the bipolar axons. The OFF-centre A2 amacrine cell response is then fed to OFF-centre ganglion cell dendrites. If the A2 cell makes inhibitory synapses upon ganglion cells, as is likely because it is thought to be a GABA-ergic cell type, 4 8 it might function in a dis inhibitory role to the centre response. Alternatively, A2 cells, despite being small-field types, might have a role in the generation of antagonistic surrounds of ganglion cells. 6 D A2 cells receive a great many amacrine inputs to their dendritic trees which could be from wider field cells than they are themselves. See text for detatled ...
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... intracellular responses of five varieties of wide-field amacrine cell and the medium-field ama crine ACh 'starburst' amacrines are shown in Fig. 9. A17 is the reciprocal amacrine cell of the rod system. As predicted from its input, seen by electron microscopy to be predominantly from rod bipolar cells, it is driven almost exclusively by rod-matched stimulating conditions. In the figure (Fig. 9, A17), rather than a slit mapped receptive field, an intensity series is shown using wavelengths of light matched for rods at rod and cone stimulating wavelengths. The responses at each light intensity superimpose, thus indicating that only a single receptor mechanism is present -that due to the rods. At all intensities the response is a depolarisation and up to the highest intensities (bottom trace) essentially a slow potential response. At the highest light intensity the response becomes slightly transient although there is a depolarising plateau phase. The response now resembles that of its input neuron, the rod bipolar cell? O A17 cells, however, do not appear to have inhibitory surrounds, although they do exhibit spatially dependent characteristics in their response amplitudes on stimulation with a surround. 3 o Amacrine cells A19, A22 and A23 are all transient depolarising ON-OFF cells. Such cells have been difficult to record long-term responses from and the example illustrated (Fig. 9, A19) is one of the longest held and thus a receptive field was mapped. A22 ...
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... intracellular responses of five varieties of wide-field amacrine cell and the medium-field ama crine ACh 'starburst' amacrines are shown in Fig. 9. A17 is the reciprocal amacrine cell of the rod system. As predicted from its input, seen by electron microscopy to be predominantly from rod bipolar cells, it is driven almost exclusively by rod-matched stimulating conditions. In the figure (Fig. 9, A17), rather than a slit mapped receptive field, an intensity series is shown using wavelengths of light matched for rods at rod and cone stimulating wavelengths. The responses at each light intensity superimpose, thus indicating that only a single receptor mechanism is present -that due to the rods. At all intensities the response is a depolarisation and up to the highest intensities (bottom trace) essentially a slow potential response. At the highest light intensity the response becomes slightly transient although there is a depolarising plateau phase. The response now resembles that of its input neuron, the rod bipolar cell? O A17 cells, however, do not appear to have inhibitory surrounds, although they do exhibit spatially dependent characteristics in their response amplitudes on stimulation with a surround. 3 o Amacrine cells A19, A22 and A23 are all transient depolarising ON-OFF cells. Such cells have been difficult to record long-term responses from and the example illustrated (Fig. 9, A19) is one of the longest held and thus a receptive field was mapped. A22 ...
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... ACh-a cells receive synaptic input to their proximal dendrites from a cone bipolar cell of sublamina a (presumably an OFF-centre cone bipolar), from ON-centre All amacrine cell lobular appendages and many unknown amacrine cells. At the ACh-a cell's synapses to the upper tier of ON OFF, bistratified ganglion cells, often a reciprocal, putatively GABA-ergic amacrine cell is involved in a local circuit (Fig. 12E, "V-A). The GABA amacrine is postsynaptic to a cone bipolar input, with a reciprocal synapse, and presynaptic to the ganglion cell dendrite in the vicinity of the ACh-a cell's synapses upon the ganglion cell. 6 5 The mirror-symmetric, ON centre ACh-b cell makes similar synapses with the lower tier of dendrites of the bistratified ON-OFF directionally selective (DS) ganglion cell (Fig. 12E, DS G, right). In this case the bipolar cell involved in the direct synapses and in the GABA-ergic amacrine local circuit is presumably an ON-centre cone bipolar cell. It is possible that the monostratified ON DS ganglion cell is also driven by ACh-b input (Fig. 12, DS G, left). 65 ACh amacrine cells are thus thought to be involved in the generation of DS in certain retinal ganglion cells, particularly in rabbits and turtles with visual streak topography. They may not be as well developed in foveal-based retinas such as cat and ...
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... ACh-a cells receive synaptic input to their proximal dendrites from a cone bipolar cell of sublamina a (presumably an OFF-centre cone bipolar), from ON-centre All amacrine cell lobular appendages and many unknown amacrine cells. At the ACh-a cell's synapses to the upper tier of ON OFF, bistratified ganglion cells, often a reciprocal, putatively GABA-ergic amacrine cell is involved in a local circuit (Fig. 12E, "V-A). The GABA amacrine is postsynaptic to a cone bipolar input, with a reciprocal synapse, and presynaptic to the ganglion cell dendrite in the vicinity of the ACh-a cell's synapses upon the ganglion cell. 6 5 The mirror-symmetric, ON centre ACh-b cell makes similar synapses with the lower tier of dendrites of the bistratified ON-OFF directionally selective (DS) ganglion cell (Fig. 12E, DS G, right). In this case the bipolar cell involved in the direct synapses and in the GABA-ergic amacrine local circuit is presumably an ON-centre cone bipolar cell. It is possible that the monostratified ON DS ganglion cell is also driven by ACh-b input (Fig. 12, DS G, left). 65 ACh amacrine cells are thus thought to be involved in the generation of DS in certain retinal ganglion cells, particularly in rabbits and turtles with visual streak topography. They may not be as well developed in foveal-based retinas such as cat and ...
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... ACh-a cells receive synaptic input to their proximal dendrites from a cone bipolar cell of sublamina a (presumably an OFF-centre cone bipolar), from ON-centre All amacrine cell lobular appendages and many unknown amacrine cells. At the ACh-a cell's synapses to the upper tier of ON OFF, bistratified ganglion cells, often a reciprocal, putatively GABA-ergic amacrine cell is involved in a local circuit (Fig. 12E, "V-A). The GABA amacrine is postsynaptic to a cone bipolar input, with a reciprocal synapse, and presynaptic to the ganglion cell dendrite in the vicinity of the ACh-a cell's synapses upon the ganglion cell. 6 5 The mirror-symmetric, ON centre ACh-b cell makes similar synapses with the lower tier of dendrites of the bistratified ON-OFF directionally selective (DS) ganglion cell (Fig. 12E, DS G, right). In this case the bipolar cell involved in the direct synapses and in the GABA-ergic amacrine local circuit is presumably an ON-centre cone bipolar cell. It is possible that the monostratified ON DS ganglion cell is also driven by ACh-b input (Fig. 12, DS G, left). 65 ACh amacrine cells are thus thought to be involved in the generation of DS in certain retinal ganglion cells, particularly in rabbits and turtles with visual streak topography. They may not be as well developed in foveal-based retinas such as cat and ...
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... is generally agreed now that the IPL can be subdivided into five equi-thickness strata or sub layers 3 into which amacrine, bipolar and ganglion cell processes can be assigned. All these cell types are now classified primarily on the basis of the stratum or strata of the IPL in which their dendrites or axons are located. This is because, as will become clear later, the IPL of vertebrate retinas can be divided up into areas of neuropil where specific cells are put into synaptic contacts and form circuits only with cells earmarked for a particular functional role. Many varieties of amacrine cells, as well as bipolar and ganglion cells, are monostratified, i.e. restricted to a single stratum, while others are bi-or tri-stratified. When amacrine or ganglion cell processes pass through all the strata of the IPL from distal to proximal or vice versa, the I are called diffuse cells. Superimposed upon Cajal's five strata subdivision of the IPL, is a sublaminar division of the IPL that serves a functional purpose. The first two strata, 1-2, are known as sublamina a of the IPL, while strata 3-5 are known as sublamina b by this scheme. 19 Sublamina a contains bipolar axons and ganglion cell connections that lead to OFF-centre ganglion cell physiology, while sublamina b contains bipolar to ganglion cell connections resulting in ON-centre ganglion cell physiology, z° Fig. 1 shows micrographs of two important amacrine cell types of the retina that have in common that they are monostratified yet are completely different in appearance and dendritic tree shape and size. The dopaminergic amacrine cell type (Fig. 1a), labelled Toh here because such cells have been revealed by immunostaining with an antibody directed against tyrosine hydroxylase, is essentially mono stratified in stratum 1 of the IPL (closest to the inner nuclear layer, INL). It is a wide field cell with processes that overlap and branch forming a densely packed network of processes that leave only few 'holes' for other amacrine cell bodies and major dendrites to pass through. In contrast, the cells labelled ACh, taken from an intracellular Lucifer yellow staining study by Vaney, 21 are examples of cholinergic 'starburst' amacrine cells of the rabbit retina (ACh-b types) (Fig. 1b). These amacrine cells have cell bodies in the ganglion cell layer, are monostratified on the stratum 3/4 border of the IPL (in sublamina b), are medium-field in size and have tremendous overlap of their dendritic trees such that as many as 70 cells overlap a single central cell in peripheral retina. 22 • 23 ACh-a type cells (not shown) are mirror images of the ACh-b types, differing only in their slightly larger dendritic tree sizes (13% larger) at corresponding retinal locations, their different stratification in the IPL and placement of their cell bodies in the INL in more typical amacrine cell fashion. They stratify on the stratum 112 border in sublamina a of the neuropil and their overlap values can reach 90 or more. ...
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... is generally agreed now that the IPL can be subdivided into five equi-thickness strata or sub layers 3 into which amacrine, bipolar and ganglion cell processes can be assigned. All these cell types are now classified primarily on the basis of the stratum or strata of the IPL in which their dendrites or axons are located. This is because, as will become clear later, the IPL of vertebrate retinas can be divided up into areas of neuropil where specific cells are put into synaptic contacts and form circuits only with cells earmarked for a particular functional role. Many varieties of amacrine cells, as well as bipolar and ganglion cells, are monostratified, i.e. restricted to a single stratum, while others are bi-or tri-stratified. When amacrine or ganglion cell processes pass through all the strata of the IPL from distal to proximal or vice versa, the I are called diffuse cells. Superimposed upon Cajal's five strata subdivision of the IPL, is a sublaminar division of the IPL that serves a functional purpose. The first two strata, 1-2, are known as sublamina a of the IPL, while strata 3-5 are known as sublamina b by this scheme. 19 Sublamina a contains bipolar axons and ganglion cell connections that lead to OFF-centre ganglion cell physiology, while sublamina b contains bipolar to ganglion cell connections resulting in ON-centre ganglion cell physiology, z° Fig. 1 shows micrographs of two important amacrine cell types of the retina that have in common that they are monostratified yet are completely different in appearance and dendritic tree shape and size. The dopaminergic amacrine cell type (Fig. 1a), labelled Toh here because such cells have been revealed by immunostaining with an antibody directed against tyrosine hydroxylase, is essentially mono stratified in stratum 1 of the IPL (closest to the inner nuclear layer, INL). It is a wide field cell with processes that overlap and branch forming a densely packed network of processes that leave only few 'holes' for other amacrine cell bodies and major dendrites to pass through. In contrast, the cells labelled ACh, taken from an intracellular Lucifer yellow staining study by Vaney, 21 are examples of cholinergic 'starburst' amacrine cells of the rabbit retina (ACh-b types) (Fig. 1b). These amacrine cells have cell bodies in the ganglion cell layer, are monostratified on the stratum 3/4 border of the IPL (in sublamina b), are medium-field in size and have tremendous overlap of their dendritic trees such that as many as 70 cells overlap a single central cell in peripheral retina. 22 • 23 ACh-a type cells (not shown) are mirror images of the ACh-b types, differing only in their slightly larger dendritic tree sizes (13% larger) at corresponding retinal locations, their different stratification in the IPL and placement of their cell bodies in the INL in more typical amacrine cell fashion. They stratify on the stratum 112 border in sublamina a of the neuropil and their overlap values can reach 90 or more. ...
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... is generally agreed now that the IPL can be subdivided into five equi-thickness strata or sub layers 3 into which amacrine, bipolar and ganglion cell processes can be assigned. All these cell types are now classified primarily on the basis of the stratum or strata of the IPL in which their dendrites or axons are located. This is because, as will become clear later, the IPL of vertebrate retinas can be divided up into areas of neuropil where specific cells are put into synaptic contacts and form circuits only with cells earmarked for a particular functional role. Many varieties of amacrine cells, as well as bipolar and ganglion cells, are monostratified, i.e. restricted to a single stratum, while others are bi-or tri-stratified. When amacrine or ganglion cell processes pass through all the strata of the IPL from distal to proximal or vice versa, the I are called diffuse cells. Superimposed upon Cajal's five strata subdivision of the IPL, is a sublaminar division of the IPL that serves a functional purpose. The first two strata, 1-2, are known as sublamina a of the IPL, while strata 3-5 are known as sublamina b by this scheme. 19 Sublamina a contains bipolar axons and ganglion cell connections that lead to OFF-centre ganglion cell physiology, while sublamina b contains bipolar to ganglion cell connections resulting in ON-centre ganglion cell physiology, z° Fig. 1 shows micrographs of two important amacrine cell types of the retina that have in common that they are monostratified yet are completely different in appearance and dendritic tree shape and size. The dopaminergic amacrine cell type (Fig. 1a), labelled Toh here because such cells have been revealed by immunostaining with an antibody directed against tyrosine hydroxylase, is essentially mono stratified in stratum 1 of the IPL (closest to the inner nuclear layer, INL). It is a wide field cell with processes that overlap and branch forming a densely packed network of processes that leave only few 'holes' for other amacrine cell bodies and major dendrites to pass through. In contrast, the cells labelled ACh, taken from an intracellular Lucifer yellow staining study by Vaney, 21 are examples of cholinergic 'starburst' amacrine cells of the rabbit retina (ACh-b types) (Fig. 1b). These amacrine cells have cell bodies in the ganglion cell layer, are monostratified on the stratum 3/4 border of the IPL (in sublamina b), are medium-field in size and have tremendous overlap of their dendritic trees such that as many as 70 cells overlap a single central cell in peripheral retina. 22 • 23 ACh-a type cells (not shown) are mirror images of the ACh-b types, differing only in their slightly larger dendritic tree sizes (13% larger) at corresponding retinal locations, their different stratification in the IPL and placement of their cell bodies in the INL in more typical amacrine cell fashion. They stratify on the stratum 112 border in sublamina a of the neuropil and their overlap values can reach 90 or more. ...
Similar publications
Much of the computational power of the retina derives from the activity of amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory interneurons. Here, we identify an ON-type orientation-selective, wide-field, polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its orientation selectivity arises from the...
Citations
... Mapping these pathways requires tools to characterize structurefunction relationships with subcellular resolution. Previous studies of dendritic processing have used subcellular calcium imaging to understand the extent of signal spread in amacrine cell arbors [11][12][13] while serial section electron microscopy has been used to map the fine-scale distribution of synaptic connections across amacrine cell arbors [14][15][16][17] . ...
VGluT3-expressing mouse retinal amacrine cells (VG3s) respond to small-object motion and connect to multiple types of bipolar cells (inputs) and retinal ganglion cells (RGCs, outputs). Because these input and output connections are intermixed on the same dendrites, making sense of VG3 circuitry requires comparing the distribution of synapses across their arbors to the subcellular flow of signals. Here, we combine subcellular calcium imaging and electron microscopic connectomic reconstruction to analyze how VG3s integrate and transmit visual information. VG3s receive inputs from all nearby bipolar cell types but exhibit a strong preference for the fast type 3a bipolar cells. By comparing input distributions to VG3 dendrite responses, we show that VG3 dendrites have a short functional length constant that likely depends on inhibitory shunting. This model predicts that RGCs that extend dendrites into the middle layers of the inner plexiform encounter VG3 dendrites whose responses vary according to the local bipolar cell response type.
... Dopamine is also a major neurotransmitter in the retina [36,37], where it is a major regulator of light adaptation [38], eye growth [39], circadian rhythms [40] and neuronal cell survival [41]. Analogous to dopaminergic neurons in the SNpc, a subclass of inhibitory neurons called amacrine cells locally produce and release dopamine within the retina [31,42]. Several groups have reported a loss of amacrine cells and consequent decreased retinal dopamine levels in PD, which have been linked to compromised contrast sensitivity and colour vision [43]. ...
... Dopaminergic, or A18, amacrine cells, with their cell bodies localised mainly to the inner plexiform layer, stained strongly for TH [42,67] and were found to be spread evenly across the retina of both WT and HOM mice at 6 months of age. Whilst THpositive neuronal loss has been reported in the substantia nigra pars compacta (SNpc) of A53T mice older than 6 months of age [52,55,68] (8-12 months), we did not observe a difference in TH-positive amacrine cell numbers in 6-month-old A53T mice ( Figure 1E). ...
Background: Loss of substantia nigra dopaminergic cells and alpha-synuclein (α-syn)-rich intraneuronal deposits within the central nervous system are key hallmarks of Parkinson’s disease (PD). Levodopa (L-DOPA) is the current gold-standard treatment for PD. This study aimed to evaluate in vivo retinal changes in a transgenic PD model of α-syn overexpression and the effect of acute levodopa (L-DOPA) treatment. Methods: Anaesthetised 6-month-old mice expressing human A53T alpha-synuclein (HOM) and wildtype (WT) control littermates were intraperitoneally given 20 mg/kg L-DOPA (50 mg levodopa, 2.5 mg benserazide) or vehicle saline (n = 11–18 per group). In vivo retinal function (dark-adapted full-field ERG) and structure (optical coherence tomography, OCT) were recorded before and after drug treatment for 30 min. Ex vivo immunohistochemistry (IHC) on flat-mounted retina was conducted to assess tyrosine hydroxylase (TH) positive cell counts (n = 7–8 per group). Results: We found that photoreceptor (a-wave) and bipolar cell (b-wave) ERG responses (p < 0.01) in A53T HOM mice treated with L-DOPA grew in amplitude more (47 ± 9%) than WT mice (16 ± 9%) treated with L-DOPA, which was similar to the vehicle group (A53T HOM 25 ± 9%; WT 19 ± 7%). While outer retinal thinning (outer nuclear layer, ONL, and outer plexiform layer, OPL) was confirmed in A53T HOM mice (p < 0.01), L-DOPA did not have an ameliorative effect on retinal layer thickness. These findings were observed in the absence of changes to the number of TH-positive amacrine cells across experiment groups. Acute L-DOPA treatment transiently improves visual dysfunction caused by abnormal alpha-synuclein accumulation. Conclusions: These findings deepen our understanding of dopamine and alpha-synuclein interactions in the retina and provide a high-throughput preclinical framework, primed for translation, through which novel therapeutic compounds can be objectively screened and assessed for fast-tracking PD drug discovery.
... [101] Later, additional sources of dopamine in the vertebrate retina include dopaminergic amacrine cells and Müller cells. [101][102][103][104] Müller cells are particularly interesting given their potential roles in foveal morphogenesis. During retinal development, L-DOPA, which can be converted to dopamine by DOPA decarboxylase, has been shown to regulate the timing of cell division in retinal precursor cells, which is important for the specification of different cell types. ...
The human fovea is known for its distinctive pit‐like appearance, which results from the displacement of retinal layers superficial to the photoreceptors cells. The photoreceptors are found at high density within the foveal region but not the surrounding retina. Efforts to elucidate the mechanisms responsible for these unique features have ruled out cell death as an explanation for pit formation and changes in cell proliferation as the cause of increased photoreceptor density. These findings have led to speculation that mechanical forces acting within and on the retina during development underly the formation of foveal architecture. Here we review eye morphogenesis and retinal remodeling in human embryonic development. Our meta‐analysis of the literature suggests that fovea formation is a protracted process involving dynamic changes in ocular shape that start early and continue throughout most of human embryonic development. From these observations, we propose a new model for fovea development.
... Moreover, the third conducting system originates from a heterogeneous population of retinal ganglion cells, among which are bistratifi ed ganglion cells (for review see [Merkul'eva, 2021]). It is of note that these are the main postsynaptic targets of acetylcholine amacrine cells [Famiglietti, 1987;Kolb, 1997], the generators of retinal waves. Another important fact: there is evidence supporting the view that the geniculate level of the third conducting channel develops earlier, as compared with the magnocellular and parvocellular channels. ...
... This far-surround modulation is mediated by wide-field GABAergic amacrine cells (or polyaxonal amacrine cells). The wide-field cell is characterized by unique long axon-like, sparse branching dendritic processes extending several millimeters, and Na + spiking drives the spread of activity along the long process (Kolb, 1997;Lin and Masland, 2006;Greschner et al., 2014) (Fig. 5B). The postsynaptic partners of wide-field cells are not only retinal ganglion cells, but also non-wide-field amacrine and bipolar cells (Marc and Liu, 2000). ...
The retinal neuronal circuit is the first stage of visual processing in the central nervous system. The efforts of scientists over the last few decades indicate that the retina is not merely an array of photosensitive cells, but also a processor that performs various computations. Within a thickness of only ~200µm, the retina consists of diverse forms of neuronal circuits, each of which encodes different visual features. Since the discovery of direction-selective cells by Horace Barlow and Richard Hill, the mechanisms that generate direction selectivity in the retina have remained a fascinating research topic. This review provides an overview of recent advances in our understanding of direction-selectivity circuits. Beyond the conventional wisdom of direction selectivity, emerging findings indicate that the retina utilizes complicated and sophisticated mechanisms in which excitatory and inhibitory pathways are involved in the efficient encoding of motion information. As will become evident, the discovery of computational motifs in the retina facilitates an understanding of how sensory systems establish feature selectivity.
... As the most diverse retinal interneurons, amacrine cells perform a variety of functions in the visual integration, which are dictated by the spatial range of neurites (27)(28)(29). We investigated the lateral field and axial stratification of SHG+ amacrine cells. ...
We describe a novel method for visualizing the network of axons in the unlabeled fresh wholemount retina. The intrinsic radiation of second harmonic generation (SHG) was utilized to visualize single axons of all major retinal neurons, i.e. photoreceptors, horizontal cells, bipolar cells, amacrine cells, and the retinal ganglion cells. The cell types of SHG + axons were determined using transgenic GFP/YFP mice. New findings were obtained with retinal SHG imaging: Müller cells do not maintain uniformly polarized microtubules in the processes; SHG + axons of bipolar cells terminate in the inner plexiform layer (IPL) in a subtype-specific manner; a subset of amacrine cells, presumably the axon-bearing types, emits SHG; and the axon-like neurites of amacrine cells provide a cytoskeletal scaffolding for the IPL stratification. To demonstrate the utility, retinal SHG imaging was applied for testing whether the inner retina is preserved in glaucoma, using DBA/2 mice as a model of glaucoma and DBA/2-Gpnmb + as the non-glaucomatous control. It was found that the morphology of the inner retina was largely intact in glaucoma and the pre-synaptic compartments to the retinal ganglion cells were uncompromised. It proves retinal SHG imaging as a promising technology for studying the physiological and diseased retinas in 3D.
... As the most diverse retinal interneurons, amacrine cells perform a variety of functions in the visual integration, which are dictated by the spatial range of neurites [27][28][29] . We investigated the lateral field and axial stratification of SHG+ amacrine cells. ...
We describe a novel microscopy for studying the network of axons in the unlabeled fresh wholemount retina. The intrinsic radiation of second harmonic generation (SHG) was utilized to visualize single axons of all major retinal neurons, i.e., photoreceptors, horizontal cells, bipolar cells, amacrine cells, and the retinal ganglion cells. The cell types of SHG+ axons were determined using transgenic GFP/YFP mice. New findings were obtained with retinal SHG imaging: Müller cells do not maintain uniformly polarized microtubules in the processes; SHG+ axons of bipolar cells terminate in the inner plexiform layer (IPL) in a subtype-specific manner; a subset of amacrine cells, presumably the axon-bearing types, emits SHG; and the axon-like neurites of amacrine cells provide a cytoskeletal scaffolding for the IPL stratification. To demonstrate the utility, retinal SHG imaging was applied for testing whether the inner retina is preserved in glaucoma, using DBA/2 mice as a model of glaucoma and DBA/2- Gpnmb+ as the non-glaucomatous control. It was found that the morphology of the inner retina was largely intact in glaucoma and the pre-synaptic compartments to the retinal ganglion cells were uncompromised. It proves retinal SHG imaging as a promising technology for studying the physiological and diseased retina in 3D.
... TH-positive amacrine cells assessed via immunohistochemistry were localised to the inner retina ( Fig. 1A-F), between the outer and inner plexiform layers 42 More severe effects were evident at 45 days after MPTP injection as shown by the average ERG waveforms in Figs. 3B,E and 4B,E. ...
In addition to well characterized motor symptoms, visual disturbances are increasingly recognized as an early manifestation in Parkinson’s disease (PD). A better understanding of the mechanisms underlying these changes would facilitate the development of vision tests which can be used as preclinical biomarkers to support the development of novel therapeutics for PD. This study aims to characterize the retinal phenotype of a mouse model of dopaminergic dysfunction and to examine whether these changes are reversible with levodopa treatment. We use a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to characterize the neurotoxic effects of MPTP on in vivo retinal function (electroretinography, ERG), retinal structure (optical coherence tomography, OCT) and retinal dopaminergic cell number (tyrosine hydroxylase immunohistochemistry, IHC) at two time points (21 and 45 days) post MPTP model induction. We also investigate the effect of levodopa (L-DOPA) as a proof-of-principle chronic intervention against MPTP-induced changes in the retina. We show that MPTP decreases dopaminergic amacrine cell number (9%, p < 0.05) and that a component of the ERG that involves these cells, in particular oscillatory potential (OP) peak timing, was significantly delayed at Day 45 (7–13%, p < 0.01). This functional deficit was paralleled by outer plexiform layer (OPL) thinning ( p < 0.05). L-DOPA treatment ameliorated oscillatory potential deficits (7–13%, p < 0.001) in MPTP animals. Our data suggest that the MPTP toxin slows the timing of inner retinal feedback circuits related to retinal dopaminergic pathways which mirrors findings from humans with PD. It also indicates that the MPTP model causes structural thinning of the outer retinal layer on OCT imaging that is not ameliorated with L-DOPA treatment. Together, these non-invasive measures serve as effective biomarkers for PD diagnosis as well as for quantifying the effect of therapy.
... This is achieved through the release by Müller glia of glutamate receptor co-agonists such as Dserine [3] and glutamate itself [4], their expression of glutamate and gamma-aminobutyric acid (GABA) transporters [5][6][7], and other roles in the re-uptake, recycling and de novo synthesis of glutamate precursors [8]. Further modulation is achieved through the function of inhibitory interneurons of the retina, horizontal cells and amacrine cells, which help shape glutamatergic neurotransmission through lateral interactions with retinal neurons [9][10][11]. The retinal network is essential to vision since any impairment of this intricate, functional unit inevitably leads to the inability to process visual input. ...
Glutamate neurotransmission and metabolism are finely modulated by the retinal network, where the efficient processing of visual information is shaped by the differential distribution and composition of glutamate receptors and transporters. However, disturbances in glutamate homeostasis can result in glutamate excitotoxicity, a major initiating factor of common neurodegenerative diseases. Within the retina, glutamate excitotoxicity can impair visual transmission by initiating degeneration of neuronal populations, including retinal ganglion cells (RGCs). The vulnerability of RGCs is observed not just as a result of retinal diseases but has also been ascribed to other common neurodegenerative and peripheral diseases. In this review, we describe the vulnerability of RGCs to glutamate excitotoxicity and the contribution of different glutamate receptors and transporters to this. In particular, we focus on the N-methyl-d-aspartate (NMDA) receptor as the major effector of glutamate-induced mechanisms of neurodegeneration, including impairment of calcium homeostasis, changes in gene expression and signalling, and mitochondrial dysfunction, as well as the role of endoplasmic reticular stress. Due to recent developments in the search for modulators of NMDA receptor signalling, novel neuroprotective strategies may be on the horizon.
... In the mammalian retina, amacrine cells are the largest cohort of neurons [50][51][52]. Amacrine cells are interneurons, which provide the integration of signals that are essential to the construction of the RGC visual message sent to the brain [53]. Further, they are highly diverse and use several neurotransmitters. ...
Glaucoma is a neurodegenerative disease that leads to damage of retinal ganglion cells and the optic nerve. Patients display altered antibody profiles and increased antibody titer, e.g., against S100B. To identify the meaning of these antibodies, animals were immunized with S100B. Retinal ganglion cell loss, optic nerve degeneration, and increased glial cell activity were noted. Here, we aimed to gain more insights into the pathophysiology from a proteomic point of view. Hence, rats were immunized with S100B, while controls received sodium chloride. After 7 and 14 days, retinae were analyzed through mass spectrometry and immunohistology. Using data-independent acquisition-based mass spectrometry, we identified more than 1700 proteins on a high confidence level for both study groups, respectively. Of these 1700, 43 proteins were significantly altered in retinae after 7 days and 67 proteins revealed significant alterations at 14 days. For example, α2-macroglobulin was found significantly increased not only by mass spectrometry analysis, but also with immunohistological staining in S100B retinae at 7 and 14 days. All in all, the identified proteins are often associated with the immune system, such as heat shock protein 60. Once more, these data underline the important role of immunological factors in glaucoma pathogenesis.
