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Paired-pulse depression (PPD) of compound responses. A: PPD fen. 2) Two different mechanisms of PPD could be discrimiof compound responses at interstimulus intervals of 50 ms ( A1) and 100 ms (A2) (5 responses averaged; resting membrane potential Å 082 mV). nated. In control slices, there was weak PPD (20% reduction). B: time course of PPD for postsynaptic potentials evoked by compound In slices in which GABA B receptors were blocked by the highstimulation. Ratio of response amplitudes to 2nd stimulus over response affinity antagonist CGP55845A, a subgroup of GABAergic amplitudes to 1st stimulus (s2/s1) are plotted against interstimulus interval. terminals displayed paired-pulse facilitation rather than PPD. Each point represents the ratio s2/s1 (mean { SE) observed in the number
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"Minimal stimulation" was applied to evoke responses in an "all-or-none" fashion in presumed medium spiny neurons of rat neostriatal slices in the presence of antagonists for glutamatergic excitation. For comparison, responses were evoked in the same cells by compound stimulation. Bicuculline (30 microM) blocked responses evoked by minimal stimulat...
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... Application of focal bipolar electrical stimulation evokes a GABA-mediated IPSP with two components exhibiting a differential sensitivity to GABA B agonists (Seabrook et al. 1991). It has been suggested that the fibers that evoke GABA B agonist-insensitive synaptic potentials originate from the recurrent collaterals of spiny projection neurons (Radnikow et al. 1997). However, in studies using intrastriatal stimulation, it is difficult to separate the effects of spiny projection neurons from the GABA interneurons, which also produce strong inhibitory responses in the spiny projection neurons (Koos and Tepper 1999 ). ...
... Nevertheless, studies using intrastriatal stimulation have shown that, as in other systems, GABA synapses in the striatum are highly modifiable and display short-term activity-dependent plasticity. Both paired-pulse depression of the IPSP evoked by intrastriatal stimulation (Radnikow et al. 1997) and synaptic augmentation (Fitzpatrick et al. 2001) have been described. Thus it should be noted that the characteristics of the synaptic response described in the present study are based on the physiological characteristics of an IPSP evoked by a single action potential, and the response might be increased or decreased by the repetitive firing patterns of the presynaptic neurons. ...
The intrastriatal microcircuit is a predominantly inhibitory GABAergic network comprised of a majority of projection neurons [medium spiny neurons (MSNs)] and a minority of interneurons. The connectivity within this microcircuit is divided into two main categories: lateral connectivity between MSNs, and inhibition mediated by interneurons, in particular fast spiking (FS) cells. To understand the operation of striatum, it is essential to have a good description of the dynamic properties of these respective pathways and how they affect different types of striatal projection neurons.
We recorded from neuronal pairs, triplets, and quadruplets in slices of rat and mouse striatum and analyzed the dynamics of synaptic transmission between MSNs and FS cells. Retrograde fluorescent labeling and transgenic EGFP (enhanced green fluorescent protein) mice were used to distinguish between MSNs of the direct (striatonigral) and indirect (striatopallidal) pathways. Presynaptic neurons were stimulated with trains of action potentials, and activity-dependent depression and facilitation of synaptic efficacy was recorded from postsynaptic neurons. We found that FS cells provide a strong and homogeneously depressing inhibition of both striatonigral and striatopallidal MSN types. Moreover, individual FS cells are connected to MSNs of both types. In contrast, both MSN types receive sparse and variable, depressing and facilitating synaptic transmission from nearby MSNs. The connection probability was higher for pairs with presynaptic striatopallidal MSNs; however, the variability in synaptic dynamics did not depend on the types of interconnected MSNs. The differences between the two inhibitory pathways were clear in both species and at different developmental stages. Our findings show that the two intrastriatal inhibitory pathways have fundamentally different dynamic properties that are, however, similarly applied to both direct and indirect striatal projections.
... The average change in the mean holding current amounted to –0.9 ± 1.75 pA (P > 0.5, one-population Student's t test). These results therefore confirm previous electrophysiological as well as immunohistochemical data indicating that SONs do not express functional GABA B Rs (Seabrook et al. 1991; Calabresi et al. 1991; Radnikow et al. 1997; Ng & Yung, 2001). To corroborate this finding, we next recorded miniature IPSCs (mIPSCs) in the presence of TTX (1 μM), a specific blocker of voltage-gated sodium channels. ...
... The cartoon of supplemental figure S2 illustrates these results. GABA B R-mediated inhibition of synaptic GABA release on striatal neurons of adult rats has been documented by several groups using intracellular recording techniques (Seabrook et al. 1991; Calabresi et al. 1991; Radnikow et al. 1997). In the present study we revealed that GABA B R signalling is operative even at early stages of striatal development (as early as P7–9). ...
... Activation of GABA B Rs with baclofen reduced the amplitudes of eIPSCs in all cells and at all ages tested. With respect to GABA B R sensitivity, our data do not support the existence of two populations of GABAergic inputs as it was suggested by previous studies (adult rats: Seabrook et al. 1991; Radnikow et al. 1997). This discrepancy might be derived from the methods used (lower resolution with conventional intracellular recording techniques) and/or differences in age. ...
GABAergic medium-sized striatal output neurons (SONs) provide the principal output for the neostriatum. In vitro and in vivo data indicate that spike discharge of SONs is tightly controlled by effective synaptic inhibition. Although phasic GABAergic transmission critically depends on ambient GABA levels, the role of GABA transporters (GATs) in neostriatal GABAergic synaptic transmission is largely unknown. In the present study we aimed at elucidating the role of GAT-1 in the developing mouse neostriatum (postnatal day (P) 7-34). We recorded GABAergic postsynaptic currents (PSCs) using the whole-cell patch-clamp technique. Based on the effects of NO-711, a specific GAT-1 blocker, we demonstrate that GAT-1 is operative at this age and influences GABAergic synaptic transmission by presynaptic and postsynaptic mechanisms. Presynaptic GABA(B)R-mediated suppression of GABA release was found to be functional at all ages tested; however, there was no evidence for persistent GABA(B)R activity under control conditions, unless GAT-1 was blocked (P12-34). In addition, whereas no tonic GABA(A)R-mediated conductances were detected in SONs until P14, application of a specific GABA(A)R antagonist caused distinct tonic outward currents later in development (P19-34). In the presence of NO-711, tonic GABA(A)R-mediated currents were also observed at P7-14 and were dramatically increased at more mature stages. Furthermore, GAT-1 block reduced the median amplitude of GABAergic miniature PSCs indicating a decrease in quantal size. We conclude that in the murine neostriatum GAT-1 operates in a net uptake mode. It prevents the persistent activation of presynaptic GABA(B)Rs (P12-34) and prevents (P7-14) or reduces (P19-34) tonic postsynaptic GABA(A)R activity.
... Indeed, pharmacological analysis of the reduction of intrastriatally evoked IPSPs in MSNs by GABA B receptor agonists has revealed evidence for the existence of two discrete populations of GABAergic fibers, one of which is regulated by presynaptic GABA B receptors and one of which is not (Seabrook et al., 1991). To further address this possibility, we applied 'minimal' intrastriatal stimulation to evoke IPSPs in an 'all-or-none' fashion in MSNs (Radnikow et al., 1997). This technique restricts synaptic input to only one or a few afferent fibers. ...
... From these studies we were able to conclude that GABAergic fibers lacking GABA B receptors were those mediating stronger pairedpulse depression than those carrying GABA B receptors. Based on the fact that axon terminals of MSNs in SN carry functional GABA B receptors, we suggested that the intrastriatal fibers possessing GABA B receptors were the axon terminals of MSN collaterals, whereas the fibers without GABA B receptors, which exhibited strong pairedpulse depression, were axon terminals of local GABAergic neurons in the neostriatum ( Fig. 2A; Radnikow et al., 1997). Similarly, in SN dopamine neurons, we observed that most IPSCs evoked by minimal stimulation were abolished by baclofen 248 (5 mM). ...
... They were blocked by the GABA A receptor antagonist bicuculline (30 mM). Thus, electrical stimulation activated in this example neostriatal GABAergic fibers with GABA B autoreceptors (modified from Radnikow et al., 1997). C: The scatter plot of the same responses illustrates the increase in the ratio of the response to the second stimulation over the response to the first stimulation (s2/s1). ...
Presynaptic receptors provide plasticity to GABAergic synapses in the basal ganglia network, in which GABA neurons outnumber all other neurons. Presynaptic receptors, mostly of the metabotropic type, enhance or reduce the strength of synaptic inhibition and are activated by ligands being released from the GABA terminals themselves (autoreceptors) or by ligands coming from other sources (heteroreceptors), including the target neurons innervated by the GABA terminals. The latter mechanism, termed retrograde signaling, is given particular emphasis as far as it occurs in substantia nigra.
... Thus, in addition to regulating glutamate release through presynaptic GABA B heteroreceptors in the striatum, GABA may also exert a feedback control over its own release through presynaptic GABA B autoreceptors. There are several sources of GABA in the striatum, including the recurrent axon collaterals of spiny projection neurons, the axons of GABAergic striatal interneurons and extrinsic sources, and it has been proposed that different populations of GABAergic synapses may be differentially regulated by GABA B autoreceptors (Seabrook et al., 1991;Radnikow et al., 1997). It is clearly important to establish the identity of those terminals forming symmetrical synapses and expressing GABA B receptors because the selective expression of GABA B receptors will have significant implications for our understanding of GABA transmission in the striatum. ...
Although multiple effects of GABA(B) receptor activation on synaptic transmission in the striatum have been described, the precise locations of the receptors mediating these effects have not been determined. To address this issue, we carried out pre-embedding immunogold electron microscopy in the rat using antibodies against the GABA(B) receptor subunits, GABA(B1) and GABA(B2). In addition, to investigate the relationship between GABA(B) receptors and glutamatergic striatal afferents, we used antibodies against the vesicular glutamate transporters, vesicular glutamate transporter 1 and vesicular glutamate transporter 2, as markers for glutamatergic terminals. Immunolabeling for GABA(B1) and GABA(B2) was widely and similarly distributed in the striatum, with immunogold particles localized at both presynaptic and postsynaptic sites. The most commonly labeled structures were dendritic shafts and spines, as well as terminals forming asymmetric and symmetric synapses. In postsynaptic structures, the majority of labeling associated with the plasma membrane was localized at extrasynaptic sites, although immunogold particles were also found at the postsynaptic specialization of some symmetric, putative GABAergic synapses. Labeling in axon terminals was located within, or at the edge of, the presynaptic active zone, as well as at extrasynaptic sites. Double labeling for GABA(B) receptor subunits and vesicular glutamate transporters revealed that labeling for both GABA(B1) and GABA(B2) was localized on glutamatergic axon terminals that expressed either vesicular glutamate transporter 1 or vesicular glutamate transporter 2. The patterns of innervation of striatal neurons by the vesicular glutamate transporter 1- and vesicular glutamate transporter 2-positive terminals suggest that they are selective markers of corticostriatal and thalamostriatal afferents, respectively. These results thus provide evidence that presynaptic GABA(B) heteroreceptors are in a position to modulate the two major excitatory inputs to striatal spiny projection neurons arising in the cortex and thalamus. In addition, presynaptic GABA(B) autoreceptors are present on the terminals of spiny projection neurons and/or striatal GABAergic interneurons. Furthermore, the data indicate that GABA may also affect the excitability of striatal neurons via postsynaptic GABA(B) receptors.
... GABAergic synaptic responses described in the current study between identified spiny projection neurons in mature culture are similar to pharmacologically isolated GABAergic responses in mature striatal slices: First, the amplitude of single synaptic GABAergic PSPs shown here is in the range of single synaptic PSPs reported under minimal stimulation conditions (29). Second, synaptic augmentation (30) and paired-pulse depression (29,30) have also been described for GABAergic responses to extracellular shock stimulation in striatal projection neurons. ...
... GABAergic synaptic responses described in the current study between identified spiny projection neurons in mature culture are similar to pharmacologically isolated GABAergic responses in mature striatal slices: First, the amplitude of single synaptic GABAergic PSPs shown here is in the range of single synaptic PSPs reported under minimal stimulation conditions (29). Second, synaptic augmentation (30) and paired-pulse depression (29,30) have also been described for GABAergic responses to extracellular shock stimulation in striatal projection neurons. Furthermore, prolonged PSP decay at high-burst frequencies and plateau-like depolarization during such bursts are reminiscent of asynchronous GABA release that was also described in dual recordings from unidentified striatal neurons in dissociated cultures (31). ...
Striatal inhibition plays an important role in models of cortex-basal ganglia function and is altered in many basal ganglia diseases. The gamma-aminobutyric acid ergic spiny projection neuron comprises >95% of striatal neurons, but despite strong anatomical evidence, the electrophysiological properties and functions of their local axon collaterals are unknown. We simultaneously recorded from adjacent spiny projection neurons (<5-10 microm) in whole-cell patch mode and demonstrated a fast synaptic connection between 2669 pairs in cortex-striatum-substantia nigra organotypic cultures and 538 pairs in acute striatal slices. The synapse, which was blocked by gamma-aminobutyric acid type A antagonists, displayed a wide range of failure rates, was depolarizing at rest, and reversed above -60 mV. Presynaptic bursts of action potentials were highly correlated with total postsynaptic depolarization at rest. Synaptic transmission was optimized for burst discharge >14 Hz and showed considerable short-term plasticity, including paired-pulse depression at intervals <25 ms, intraburst facilitation, and interburst augmentation. This activity-dependent collateral interaction provides the basis for a new class of basal ganglia models in which striatal neurons cooperate as well as compete during processing of cortical inputs.
... Application of focal bipolar electrical stimulation evokes a GABA-mediated IPSP with two components exhibiting a differential sensitivity to GABA B agonists ( Seabrook et al. 1991). It has been suggested that the fibers that evoke GABA B agonist-insensitive synaptic potentials originate from the re- current collaterals of spiny projection neurons ( Radnikow et al. 1997). However, in studies using intrastriatal stimulation, it is difficult to separate the effects of spiny projection neurons from the GABA interneurons, which also produce strong in- hibitory responses in the spiny projection neurons ( Koos and Tepper 1999). ...
... Nevertheless, studies using intrastriatal stimu- lation have shown that, as in other systems, GABA synapses in the striatum are highly modifiable and display short-term ac- tivity-dependent plasticity. Both paired-pulse depression of the IPSP evoked by intrastriatal stimulation (Radnikow et al. 1997) and synaptic augmentation (Fitzpatrick et al. 2001) have been described. Thus it should be noted that the characteristics of the synaptic response described in the present study are based on the physiological characteristics of an IPSP evoked by a single action potential, and the response might be increased or de- creased by the repetitive firing patterns of the presynaptic neurons. ...
The spiny projection neurons are by far the most numerous type of striatal neuron. In addition to being the principal projection neurons of the striatum, the spiny projection neurons also have an extensive network of local axon collaterals by which they make synaptic connections with other striatal projection neurons. However, up to now there has been no direct physiological evidence for functional inhibitory interactions between spiny projection neurons. Here we present new evidence that striatal projection neurons are interconnected by functional inhibitory synapses. To examine the physiological properties of unitary inhibitory postsynaptic potentials (IPSPs), dual intracellular recordings were made from pairs of spiny projection neurons in brain slices of adult rat striatum. Synaptic interactions were found in 9 of 45 pairs of neurons using averages of 200 traces that were triggered by a single presynaptic action potential. In all cases, synaptic interactions were unidirectional, and no bidirectional interactions were detected. Unitary IPSPs evoked by a single presynaptic action potential had a peak amplitude ranging from 157 to 319 μV in different connections (mean: 277 ± 46 μV, n = 9). The percentage of failures of single action potentials to evoke a unitary IPSP was estimated and ranged from 9 to 63% (mean: 38 ± 14%, n = 9). Unitary IPSPs were reversibly blocked by bicuculline ( n = 4) and had a reversal potential of −62.4 ± 0.7 mV ( n = 5), consistent with GABA-mediated inhibition. The findings of the present study correlate very well with anatomical evidence for local synaptic connectivity between spiny projection neurons and suggest that lateral inhibition plays a significant role in the information processing operations of the striatum.
... Another mechanism responsible for short-term changes in synaptic strength is activation of neurotransmitter receptors on the presynaptic terminal. For example, activation of GABA B receptors (Calabresi et al. 1991;Radnikow et al. 1997;Seabrook et al. 1991), muscarinic acetylcholine receptors (Marchi et al. 1990;Sugita et al. 1991), metabotropic glutamate receptors (Stefani et al. 1994), or adenosine receptors (Mori et al. 1996) can decrease synaptic strength at inhibitory synapses in striatum by decreasing the amount of GABA released. Activation of these receptors decreases release either by decreasing the calcium influx into the presynaptic terminal or by interfering with mechanisms of transmitter release (Wu and Saggau 1997). ...
... Atropine did not block PPD ( Fig. 3C; 83 Ϯ 3% at 500 ms ISI; n ϭ 6; P Ͼ 0.35, 2-tailed t-test), indicating that PPD is not mediated by muscarinic acetylcholine receptors. Activation of GABA B receptors has also been shown to reduce IPSPs in striatum (Calabresi et al. 1991;Radnikow et al. 1997;Seabrook et al. 1991). We tested whether GABA B receptors mediate PPD by measuring PPD in the presence of the GABA B receptor antagonist CGP 35348 (100 M). ...
... The IPSP exhibited PPD over a wide range of ISIs, as previously reported (Radnikow et al. 1997). The time course of PPD, with its slow onset and even slower recovery, suggests it is due to activation of presynaptic metabotropic receptors. ...
Two forms of short-term plasticity at inhibitory synapses were investigated in adult rat striatal brain slices using intracellular recordings. Intrastriatal stimulation in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM) and D,L-2-amino-5-phosphonovaleric acid (50 microM) produced an inhibitory postsynaptic potential (IPSP) that reversed polarity at -76 +/- 1 (SE) mV and was sensitive to bicuculline (30 microM). The IPSP rectified at hyperpolarized membrane potentials due in part to activation of K(+) channels. The IPSP exhibited two forms of short-term plasticity, paired-pulse depression (PPD) and synaptic augmentation. PPD lasted for several seconds and was greatest at interstimulus intervals (ISIs) of several hundred milliseconds, reducing the IPSP to 80 +/- 2% of its control amplitude at an ISI of 200 ms. Augmentation of the IPSP, elicited by a conditioning train of 15 stimuli applied at 20 Hz, was 119 +/- 1% of control when sampled 2 s after the conditioning train. Augmentation decayed with a time constant of 10 s. We tested if PPD and augmentation modify the ability of the IPSP to prevent the generation of action potentials. A train of action potentials triggered by a depolarizing current injection of constant amplitude could be interrupted by stimulation of an IPSP. If this IPSP was the second in a pair of IPSPs, it was less effective in blocking spikes due to PPD. By contrast, augmented IPSPs were more effective in blocking spikes. The same results were achieved when action potentials were triggered by a depolarizing current injection of varying amplitude, a manipulation that produces nearly identical spike times from trial to trial and approximates the in vivo behavior of these neurons. These results demonstrate that short-term plasticity of inhibition can modify the output of the striatum and thus may be an important component of information processing during behaviors that involve the striatum.
... Activation of these receptors decreases presynaptic release of both glutamate and GABA, thereby reducing glutamatergic EPSPs and GABAergic IPSPs (for review see Misgeld et al., 1995). The GABA B receptor-mediated control of GABA release has been extensively studied in different areas of the brain (Pittaluga et al., 1987; Harrison, 1990; Scholz & Miller, 1991; Otis & Mody, 1992; Isaacson et al., 1993; Lambert & Wilson, 1993; Doze et al., 1995; Guyon & Leresche, 1995; Khazipov et al., 1995; Emri et al., 1996; Mouginot & Gähwiler, 1996; Radnikow et al., 1997). In the rat cerebral cortex, the GABA B receptor agonist baclofen reduced GABA release measured using [ 3 H]GABA-prelabelled synaptosomes (Pittaluga et al., 1987 ) indicating the presence of GABA B receptors on GABAergic nerve terminals. ...
... Recent studies suggest that there may be different GABA B receptor subtypes involved in the presynaptic action of GABA (Harrison, 1990; Guyon & Leresche, 1995; Emri et al., 1996). Furthermore, it has been shown that there are subsets of GABAergic interneurons insensitive to presynaptic control of transmitter release by GABA (Lambert & Wilson, 1993; Radnikow et al., 1997), and that GABA B receptors do not influence spontaneous transmitter release or GABA release induced by so-called minimal stimulation (Otis & Mody, 1992; Doze et al., 1995; Radnikow et al., 1997). In the rat neocortex, application of the GABA B receptor agonist baclofen reduces the amplitude of postsynaptic responses consisting of both EPSPs and IPSPs (Howe et al., 1987b). ...
... Recent studies suggest that there may be different GABA B receptor subtypes involved in the presynaptic action of GABA (Harrison, 1990; Guyon & Leresche, 1995; Emri et al., 1996). Furthermore, it has been shown that there are subsets of GABAergic interneurons insensitive to presynaptic control of transmitter release by GABA (Lambert & Wilson, 1993; Radnikow et al., 1997), and that GABA B receptors do not influence spontaneous transmitter release or GABA release induced by so-called minimal stimulation (Otis & Mody, 1992; Doze et al., 1995; Radnikow et al., 1997). In the rat neocortex, application of the GABA B receptor agonist baclofen reduces the amplitude of postsynaptic responses consisting of both EPSPs and IPSPs (Howe et al., 1987b). ...
The role of gamma-aminobutyric acid B (GABA(B)) receptors in the generation and maintenance of bicuculline-induced epileptiform activity in rat neocortical slices was studied using electrophysiological methods. A block of GABA(B) receptors in the presence of functional GABA(A) receptor-mediated inhibition was not sufficient to induce epileptiform activity. In the presence of the GABA(A) receptor antagonist bicuculline (10 microM) and at suprathreshold stimulation, the GABA(B) receptor antagonist CGP 35348 (10-300 microM) significantly potentiated epileptiform activity. With stimulation at threshold intensity, low concentrations of CGP 35348 (10-30 microM) potentiated bicuculline-induced activity, whereas higher concentrations (100-300 microM) invariably led to a reversible suppression of stimulus-evoked epileptiform discharges. CGP 35348 also enhanced picrotoxin-induced epileptiform activity, but at higher concentrations it was considerably less effective in suppressing such epileptiform discharges. The GABA uptake inhibitor nipecotic acid partially mimicked the actions of CGP 35348: with stimulation at threshold intensity, it reversibly suppressed bicuculline-induced epileptiform field potentials, but it did not influence epileptiform activity induced by picrotoxin. We conclude that a postsynaptic blockade of GABA(B) receptors induces an amplification of epileptiform activity in neocortical slices disinhibited by GABA(A) receptor antagonists. An additional blockade of presynaptic GABA(B) receptors, especially under conditions of weak stimulation of the neurons, reduces the inhibitory auto-feedback control of GABA release, leading to a displacement of competitive antagonists from the postsynaptic GABA(A) receptor and hence, to a suppression of epileptiform activity induced by competitive GABA(A) receptor antagonists.
... The stimulation pipette was positioned within a 100 m distance from the recorded cell within the SN R, laterally or medially to the recorded cell outside the cerebral peduncle. Stimulus intensities were selected to elicit all-or-none I PSC s (Edwards et al., 1990; Lambert and Wilson, 1993; Radnikow et al., 1997) (see Fig. 2 A). A 20 –50% proportion of failures was considered acceptable to classif y evoked I PSC s as all-or-none events. ...
GABA neurons in the substantia nigra pars reticulata receive input from GABAergic fibers originating in the forebrain. The role of dopaminergic D1 receptors located on these fibers was investigated using tight-seal whole-cell recordings from visually identified pars reticulata neurons of rat substantia nigra slices. Nondopaminergic pars reticulata neurons were characterized by their electrophysiological properties. Postsynaptic currents evoked by minimal stimulation in the presence of ionotropic glutamate receptor antagonists were blocked by bicuculline, indicating that they were GABAA IPSCs. Evoked GABAA IPSCs were potentiated by D1 receptor agonists. After application of D1 receptor agonists, miniature IPSCs [recorded in the presence of tetrodotoxin (TTX) and the Ca2+ channel blocker Cd2+] increased in frequency but not in amplitude. Effects of D1 receptor stimulation were mimicked by forskolin, as expected, if a cAMP-dependent mechanism was involved. The D1 antagonist SCH23390 blocked the effects of the agonists, and perfusion with SCH23390 resulted in a reduction of evoked IPSCs. In TTX and Cd2+, which prevented dopamine release, the D1 antagonist had no effect on miniature IPSCs. Blocking of monoamine uptake by imipramine increased the amplitude of evoked IPSCs. We conclude that dopamine released from dendrites of dopaminergic neurons enhances GABA release in the pars reticulata of the substantia nigra through D1 receptors presumably located on striatonigral afferents. These D1 receptors, thereby, can reinforce D1 receptor-mediated activation of striatal projection neurons that inhibit the inhibitory output neurons of the basal ganglia in substantia nigra.
This chapter is a review of existing evidence and current thinking in relation to the concept of surround inhibition in the basal ganglia. In the following sections, the possibility of inhibitory interactions among spiny projection neurons will be reconsidered in the light of recent evidence. Statistical considerations based on quantitative neuroanatomical fmdings suggest a low probability of synaptic connection between neighbouring neurons. Electrophysiological studies have failed to demonstrate inhibitory interactions between spiny projection neurons. Together these fmdings suggest that inhibitory interactions among spiny projection neurons are relatively sparse. This suggests that the collaterals of spiny projection neurons are not the major source of surround inhibition. Instead, feedforward inhibition by a network of GABA/parvalbumin containing intemeurons seems to explain surround inhibition at a macroscopic level. New models are needed to address the functional significance of powerful feedforward inhibition by GABA/parvalbumin containing intemeurons, and the function of sparse inhibitory interactions between spiny projection neurons.
