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Optimizing brain processing

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Alexander Thiele at Newcastle University
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Cholinergic neurons in the basal forebrain enable alert and attending brain states. A study now shows how basal forebrain activity increases coding abilities of cortical neurons and at what stages these changes occur.
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nature neuroscience volume 12 | number 11 | november 2009 1359
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Have you ever wondered what makes the
difference between the dreamy drowsy
state before nodding off in your easy chair
and that crisp appearance of the world
when fully alert? A small structure in the
basal forebrain, the nucleus basalis, is the
key. In conjunction with other subcortical
neuromodulatory systems, it has long been
thought to promote neocortical ‘energizing’,
allowing the cortex to rapidly handle
changing task demands and inputs. Artificial
activation of the nucleus basalis results in
desynchronization of neocortical activity1,
resembling states seen in alert and attending
subjects2. Nucleus basalis neurons alter their
activity in a task- and stimulus-dependent
manner, release of acetylcholine (its main
transmitter) in the cortex is tightly linked to
states of attention3, and blockade of specific
cholinergic receptors reduces attentional
modulation of cortical activity4. But how
does nucleus basalis activation and associated
acetylcholine release alter brain states? How
do they affect cortical processing and in what
sense do they optimize brain processing?
Many, often contradicting, answers have
been given to these questions over the years.
An exciting addition to the story is given by
Goard and Dan in this issue5. They found that
nucleus basalis activation increased neuronal
reliability and decreased the redundancy
of information processing. Both changes
boosted the amount of information neuronal
populations could process at any given time.
Decreased redundancy of cortical neuronal
activity was mediated through action at
muscarinic receptors in the cortex itself,
whereas increased reliability was mediated
through distributed mechanisms along the
subcortical processing pathway. These data
suggest potential mechanisms by which the
nucleus basalis might ‘sharpen’ our perception
of the world when we are fully alert.
Goard and Dan5 tested the role of
the nucleus basalis with a crucial, but
fairly simple, experiment. They recorded
neuronal activity in primary visual cortex
simultaneously from multiple neurons
and cortical layers while anesthetized rats
viewed short movie sequences, and then
they asked what changes occurred following
stimulation of the nucleus basalis. Electrical
stimulation results in increased acetylcholine
(and GABA) release at axon terminals and
this markedly influenced the responses of
visual cortical neurons. First, nucleus basalis
stimulation altered the power spectrum of
the local field potential in V1, increasing the
spectral power at higher frequencies (10–100
Hz) at the expense of lower frequencies,
reminiscent of the electroencephalography
changes seen in earlier studies1 and when
subjects go from rest state to active states2.
Nucleus basalis stimulation increased
the neuronal activity in layers 4–6, while
slightly reducing the activity in layers 2 and
3. Irrespective of increased or decreased
activity, neurons responded much more
reliably and time locked to specific events in
the movie sequences. Intriguingly, the activity
of simultaneously recorded neurons was less
correlated. Increased reliability increased the
amount of information a given neuron could
encode, whereas decreased interneuronal
correlation reduced the redundancy of
information in a pool of neurons. Both
mechanisms increased the coding capacity
of neuronal populations. The nucleus basalis
can thus improve information processing in
the cortex.
Optimizing brain processing
Alexander Thiele
Cholinergic neurons in the basal forebrain enable alert and attending brain states. A study now shows how basal
forebrain activity increases coding abilities of cortical neurons and at what stages these changes occur.
Thalamocortical
afferents
Lateral
connections
mAChR nAChR
+ACh +ACh
a
Nucleus
basalis
b
Cortex
ACh
GABA
Sensory
periphery
Thalamic
relay nucleus
Reticular
thalamic
nucleus
ACh
GABA
GABA
Decorrelation? Increased reliability?
Glu
Glu
The author is at the Institute of Neuroscience,
Newcastle University, Newcastle upon Tyne, UK.
e-mail: alex.thiele@ncl.ac.uk
Figure 1 Mechanism by which decreased correlation and increased response reliability could be
mediated by activation of the nucleus basalis. (a) Cortical neurons make extensive connections
in an area (lateral connection) in addition to receiving feedforward input (termed thalamocortical
afferents here). These connections can be independently modulated by acetylcholine (ACh). ACh
can act on muscarinic receptors (mAChRs) in the presynaptic terminal to reduce their efficacy.
This would reduce crosstalk between cortical neurons and consequently affect their correlation, as
demonstrated by Goard and Dan5. ACh can also increase the synaptic efficacy of thalamocortical
synapses by acting on nicotinic receptors (nAChR). This could, in principle, increase response
reliability, but Goard and Dan’s study suggests an alternative mechanism. (b) In addition to its
cortical projection, the nucleus basalis has strong connections to the reticular thalamic nucleus,
the gatekeeper of the thalamus. The reticular thalamic nucleus inhibits the flow from the sensory
periphery to the cortex at the thalamic relay stage. The nucleus basalis can inhibit the activity
in the reticular thalamic nucleus through GABAergic and cholinergic mechanisms and could
thus control the gatekeeper. An active nucleus basalis would promote the flow from the sensory
periphery to the cortex by disinhibiting neurons in the relay nucleus. This could result in increased
response reliability in the cortex and the relay nucleus itself, consistent with the results by Goard
and Dan5. Although the appeal of these schematics lies in their simplicity, many more mechanisms
will be at work. Up and down arrows in a relate to increased and decreased synaptic efficacy when
ACh levels are increased. Green arrows in b indicate excitatory connection and red arrows indicate
inhibitory connections. The main transmitters involved in the respective transmissions and their
predominant respective actions are indicated (green, excitation; red, inhibition). Glu, glutamate.
© 2009 Nature America, Inc. All rights reserved.
1360 volume 12 | number 11 | november 2009 nature neuroscience
news and views
suggesting that different mechanisms are
at work. However, it was recently found
that correlation of activity between V4
neurons was reduced when attention was
directed to their receptive field15. The
closest direct link between attention and
this result is the finding that attentional
modulation in V1 of the macaque requires
active muscarinic receptors. In one study4,
blockade reduced attentional modulation in
V1. But this study4 did not analyze whether
muscarinic blockade reduced decorrelation
or whether acetylcholine application caused
a decorrelation. In addition, response
reliability did not seem affected in this
study4, so the validity of this link remains to
be determined.
The list of open questions clearly does not
end here, but this short list demonstrates
how much more there is to be learnt before
we arrive at a mechanistic account of how the
nucleus basalis, acetylcholine and attention
modulate visual cortical processing. The
study by Goard and Dan5 contributes some
important information to this area of study
and maybe even suggests how the nucleus
basalis helps to abolish that afternoon
drowsiness.
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(2009).
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1222–1229 (1992).
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Science 324, 1207–1210 (2009).
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55, 131–141 (2007).
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Neurosci. 7, 982–991 (2004).
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63, 879–888 (2009).
controls the entry of signals to the cortex8.
An active thalamic reticular nucleus inhibits
thalamic relay nuclei and thus the flow of
sensory information to specific cor tical
areas. Notably, the nucleus basalis can inhibit
neurons in the thalamic reticular nucleus
through its GABAergic and cholinergic
projections9, thereby disinhibiting the
thalamic relay nucleus and providing the
cortex with sensory input (Fig. 1b). Does the
nucleus basalis control the gatekeeper?
The effects of acetylcholine on cortical
and subcortical activity have been of interest
for quite some time. Early studies have
suggested that acetylcholine application and
nucleus basalis stimulation can increase the
signal-to-noise ratio of neuronal responses10
and sharpen tuning curves10, effects that, at
first glance, are reminiscent of the increased
response reliability reported by Goard and
Dan5. However, the authors were unable
to find systematic alterations of tuning
characteristics of cortical neurons, which is
consistent with some recent reports11. Future
studies are required to determine the reasons
for these discrepant results.
How do these findings relate to states of
attention? This simple question opens a
can of worms. Although there are notable
similarities between the effects seen here and
those reported when animals are engaged in
attention-demanding tasks, there are also
differences or at least open questions. The
increase in gamma power in the LFP that
was induced by nucleus basalis stimulation is
reminiscent of increased gamma power seen
in macaque V4 and frontal eye fields12 when
attention is directed to the receptive field of
the neurons being studied. But is this increase
with attention supported or mediated by
cholinergic mechanisms? The increased
response reliability is compatible with the
effects of attention, where attention increases
the firing rate and can reduce the response
variance13. However, the finding that nucleus
basalis stimulation reduces activity in layer
2/3 of V1 is incompatible with results
from V1 in task-performing monkeys4.
As to decorrelation of activity, recordings
from V1 show that correlation between
neurons is not decreased with attention14,
What are the mechanisms behind this
increased coding ability? Cortical neurons
make extensive connections with their
neighbors, and the extensive crosstalk is a
possible source for correlated activity levels.
Acetylcholine can reduce the efficacy of
these connections by activating presynaptic
muscarinic receptors6. Reduced synaptic
efficacy of lateral connections would reduce
crosstalk and thus decorrelate cortical
activity (Fig. 1a). To test this scenario,
Goard and Dan5 applied the muscarinic
antagonist atropine sulfate. Nucleus basalis
stimulation in the presence of muscarinic
receptor blockade indeed resulted in less
decorrelation of cortical neurons.
The increased response reliability was not
affected by muscarinic receptor blockade, but
this was hardly surprising. To determine the
mechanisms of increased response reliability,
one might rather want to direct attention to
nicotinic receptors in visual cortex, which
reside mostly on thalamocortical terminals.
The activation of these receptors increases
thalamocortical transmission efficacy7.
Thus, incoming stimuli should be processed
more effectively when nicotinic receptors are
activated by acetylcholine. However, when
Goard and Dan5 tested this possibility by
blocking the nicotinic receptors, they found
no reduction in response reliability when
nucleus basalis was electrically stimulated.
This finding suggests that the increased
response reliability associated with nucleus
basalis stimulation occurs at subcortical
stages before the information reaches the
cortex. Goard and Dan5 confirmed this
by recording from the lateral geniculate
body of the thalamus with and without
nucleus basalis stimulation. Nucleus basalis
stimulation resulted in increased response
reliability at this stage of processing. These
data suggest that the nucleus basalis affects
neuronal activity at different levels and has a
variety of ways to constrain how information
is processed.
One way that the nucleus basalis could alter
response reliability at the subcortical level is
through its connections with the thalamic
reticular nucleus. The thalamic reticular
nucleus is often viewed as a gatekeeper that
© 2009 Nature America, Inc. All rights reserved.
... Attention exerts modulatory effects on the CRF, which are represented by the response gain, contrast gain, and additive models of attention [2][3][4] . One could argue that the shifts in PNE that were observed in V4 over the course of learning might not have been due specifically to improvements at the perceptual level on the contrast discrimination task, but rather to a general effect of attention. ...
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... Anatomically, the basal nucleus of Meynert (BNM), lying anterior to the thalamus and basal ganglia, contains the cell bodies of neurons that provide cholinergic innervation of the cerebral cortex (Mufson, Ginsberg, Ikonomovic, & DeKosky, 2003;Raghanti et al., 2011;Whitehouse et al., 1982;Zaborszky et al., 2015;Zaborszky, van den Pol, & Gyengesi, 2012). Neuronal activities in BNM have been associated with memory formation (Richardson & DeLong, 1988), attention (Muir, Page, Sirinathsinghji, Robbins, & Everitt, 1993;Voytko et al., 1994), and the regulation of arousal and sleep (Thiele, 2009;Wenk, 1997). A recent empirical study indicated that BNM activation is important for improving sensory processing by increasing reliability and decreasing redundancy in the cortex and thalamus (Goard & Dan, 2009). ...
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... One could possibly link the trial-by-trial fluctuations in cortical responses examined here to trial fluctuations in attention. Indeed, attention has been shown to modulate neuronal responses and sensitivity (McAdams and Maunsell, 1999;Thiele, 2009;Cohen and Maunsell, 2009a;Gutnisky et al., 2009;Herrero et al., 2013;Treue and Maunsell, 1996) as well as response variability and pairwise correlations (Cohen and Maunsell, 2009b;Mitchell et al., 2009) in early and mid-level visual cortical areas. However, our results are inconsistent with the effects of attention for the following reasons. ...
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Brain activity during wakefulness is characterized by rapid fluctuations in neuronal responses. Whether these fluctuations play any role in modulating the accuracy of behavioral responses is poorly understood. Here, we investigated whether and how trial changes in the population response impact sensory coding in monkey V1 and perceptual performance. Although the responses of individual neurons varied widely across trials, many cells tended to covary with the local population. When population activity was in a 'low' state, neurons had lower evoked responses and correlated variability, yet higher probability to predict perceptual accuracy. The impact of firing rate fluctuations on network and perceptual accuracy was strongest 200-ms before stimulus presentation, and it greatly diminished when the number of cells used to measure the state of the population was decreased. These findings indicate that enhanced perceptual discrimination occurs when population activity is in a 'silent' response mode in which neurons increase information extraction.
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... More recently, similar studies performed with more elegant analyses have also revealed that ACh can enhance information processing through interneuronal decorrelation of V1 responses (Goard and Dan, 2009;Thiele, 2009). Such decorrelation between V1 responses is particularly evident during execution of attentional tasks in behaving monkeys (Cohen and Maunsell, 2009;Mitchell et al., 2009). ...
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Task-Related Activation of Auditory Cortex
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  • Jan 2013
Theoretical concepts of audition in conjunction with modified auditory and heterogeneous nonauditory activities found in auditory cortex during task performance point to its role as a semantic processor. Notably, these activities during each task trial reflect not only identification of auditory target features but also in many details the associations formed with other information for behavioral execution of the task. In this way the behavioral meaning of the sounds seems to be determined locally, namely what to do with a sound in a task-specific fashion. Even though many details of activation changes and activation states during a task trial need clarification, the available evidence suggests that it might be possible to recognize from these activities which basic types of logical operations were involved, for example, detection, discrimination, or categorization of sounds. Also motivational aspects related to approach or avoidance, prediction of events, and reinforcements as well as prediction errors seem to be discriminable from the activities. It is obvious that these facets of a task cannot be deduced by auditory cortex alone but only in cooperation with numerous other cortical and subcortical brain areas. Recent evidence suggests that the necessary anatomical connections are available even for primary auditory cortex but become functional only during engagement in auditory tasks. This new view on auditory cortex implies that hierarchical concepts of brain organization reserving cognitive functions to “higher order” cortices must be modified. The information flow from sensory cortex to such cortical areas is undebatable but they seem to feed information back to sensory cortex for local cognitive processing.
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EEG and single-unit techniques have been used to study the EEG correlates of cellular firing in the neocortex, n. reticularis (RT) and "specific" thalamic nuclei, and the cholinergic forebrain area (nucleus basalis, NB). Neuronal firing was related to the ongoing behavior of the rat. In addition, using a 16-channel neocortical recording/mapping system, we studied the effects of ibotenic acid lesion of NB, RT, and other thalamic nuclei on the patterns and spatial distribution of neocortical electrical activity. The majority of neurons in neocortex, NB, and RT increased their firing rates during walking, as compared to during immobility, with concurrent decrease of delta power in the neocortical EEG. During immobility, high-voltage spindles (HVS; greater than 1 mV) were occasionally recorded from the neocortex. Depth profiles of HVS and slow delta waves were different in the neocortex. Neocortical cells decreased their discharge frequency during the positive portion of delta waves recorded in layers V and VI. All cells in the neocortex and specific thalamic nuclei fired rhythmically and phase-locked to the spike component of HVS. RT neurons showed an opposite phase relationship and fired mainly during the wave component of HVS. Half of the NB neurons also showed phasic modulation with HVS. Circumscribed lesion of RT and extensive damage of other thalamic regions, including the intralaminar nuclei, suppressed HVS but had no effect on the neocortical EEG correlates of behavior. In sharp contrast, damage to the NB resulted in a dramatic increase of slow delta waves on the side of the lesion, mimicking the effect of scopolamine administration. We suggest that the NB plays a key role in neocortical arousal by directly activating the neocortex and by suppressing the rhythm generation in the RT-thalamocortical circuitry. We further suggest that the NB system may serve as a structural basis for the concept of the generalized ascending activation of Moruzzi and Magoun (1949).
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Acetylcholine contributes through muscarinic receptors to attentional modulation in V1
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Attention exerts a strong influence over neuronal processing in cortical areas. It selectively increases firing rates and affects tuning properties, including changing receptive field locations and sizes. Although these effects are well studied, their cellular mechanisms are poorly understood. To study the cellular mechanisms, we combined iontophoretic pharmacological analysis of cholinergic receptors with single cell recordings in V1 while rhesus macaque monkeys (Macaca mulatta) performed a task that demanded top-down spatial attention. Attending to the receptive field of the V1 neuron under study caused an increase in firing rates. Here we show that this attentional modulation was enhanced by low doses of acetylcholine. Furthermore, applying the muscarinic antagonist scopolamine reduced attentional modulation, whereas the nicotinic antagonist mecamylamine had no systematic effect. These results demonstrate that muscarinic cholinergic mechanisms play a central part in mediating the effects of attention in V1.
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The nucleus basalis of the basal forebrain is an essential component of the neuromodulatory system controlling the behavioral state of an animal and it is thought to be important in regulating arousal and attention. However, the effect of nucleus basalis activation on sensory processing remains poorly understood. Using polytrode recording in rat visual cortex, we found that nucleus basalis stimulation caused prominent decorrelation between neurons and marked improvement in the reliability of neuronal responses to natural scenes. The decorrelation depended on local activation of cortical muscarinic acetylcholine receptors, whereas the increased reliability involved distributed neural circuits, as evidenced by nucleus basalis-induced changes in thalamic responses. Further analysis showed that the decorrelation and increased reliability improved cortical representation of natural stimuli in a complementary manner. Thus, the basal forebrain neuromodulatory circuit, which is known to be activated during aroused and attentive states, acts through both local and distributed mechanisms to improve sensory coding.
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  • SCIENCE
Attention and Synchrony Neural activity in the visual cortex becomes synchronized with attention and other behavioral states. However, the source of this synchrony is still unknown. Gregoriou et al. (p. 1207 ) tested the hypothesis that synchronized activity from the frontal eye field is one of the causes of the synchrony in monkey visual cortical area V4 during attention. With attention, neural activity in area V4 synchronized with frontal eye field activity when a stimulus fell in a joint receptive field, but did not do so when the fields were not overlapping.
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Full-text available
  • Jan 1993
In the mammalian neocortex, the EEG reflects the state of behavioral arousal. The EEG undergoes a transformation, known as activation, during the transition from sleep to waking. Abundant evidence indicates the involvement of the neurotransmitter acetylcholine (ACh) in EEG activation; however, the cellular basis of this involvement remains unclear. We have used electrophysiological techniques with in vivo and in vitro preparations to demonstrate actions of endogenous ACh on neurons in auditory neocortex. In vivo stimulation of the nucleus basalis (NB), a primary source of neocortical ACh, (1) elicited EEG activation via cortical muscarinic receptors, (2) depolarized cortical neurons, and (3) produced a change in subthreshold membrane potential fluctuations from large-amplitude, slow (1-5 Hz) oscillations to low-amplitude, fast (20-40 Hz) oscillations. The NB-mediated change in pattern of membrane potential fluctuations resulted in a shift of spike discharge pattern from phasic to tonic. Stimulation of afferents in the in vitro neocortex elicited cholinergic actions on putative layer 5 pyramidal neurons. Acting via muscarinic receptors, endogenous ACh (1) reduced slow, rhythmic burst discharge and facilitated higher-frequency, single-spike discharge in burst-generating neurons, and (2) facilitated the appearance and magnitude of intrinsic membrane potential oscillations. These in vivo and in vitro observations suggest that neocortical activation results from muscarinic modulation of intrinsic neural oscillations and firing modes. Rhythmic-bursting pyramidal neurons in layer 5 may act as cortical pacemakers; if so, then modifying their discharge characteristics could alter local cortical networks. Larger, intercortical networks could also be modified, due to the widespread projections of NB neurons. Thus, NB cholinergic neurons may play a critical role in producing different states of neocortical function.
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Spatial Attention Decorrelates Intrinsic Activity Fluctuations in Macaque Area V4
Article
  • Sep 2009
Attention typically amplifies neuronal responses evoked by task-relevant stimuli while attenuating responses to task-irrelevant distracters. In this context, visual distracters constitute an external source of noise that is diminished to improve attended signal quality. Activity that is internal to the cortex itself, stimulus-independent ongoing correlated fluctuations in firing, might also act as task-irrelevant noise. To examine this, we recorded from area V4 of macaques performing an attention-demanding task. The firing of neurons to identically repeated stimuli was highly variable. Much of this variability originates from ongoing low-frequency (<5 Hz) fluctuations in rate correlated across the neuronal population. When attention is directed to a stimulus inside a neuron's receptive field, these correlated fluctuations in rate are reduced. This attention-dependent reduction of ongoing cortical activity improves the signal-to-noise ratio of pooled neural signals substantially more than attention-dependent increases in firing rate.
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Guarding the gateway to cortex: attention in visual thalamus
Article
  • Nov 2008
  • NATURE
The massive visual input from the eye to the brain requires selective processing of some visual information at the expense of other information, a process referred to as visual attention. Increases in the responses of visual neurons with attention have been extensively studied along the visual processing streams in monkey cerebral cortex, from primary visual areas to parietal and frontal cortex. Here we show, by recording neurons in attending macaque monkeys (Macaca mulatta), that attention modulates visual signals before they even reach cortex by increasing responses of both magnocellular and parvocellular neurons in the first relay between retina and cortex, the lateral geniculate nucleus (LGN). At the same time, attention decreases neuronal responses in the adjacent thalamic reticular nucleus (TRN). Crick argued for such modulation of the LGN by observing that it is inhibited by the TRN, and suggested that "if the thalamus is the gateway to the cortex, the reticular complex might be described as the guardian of the gateway", a reciprocal relationship we now show to be more than just hypothesis. The reciprocal modulation in LGN and TRN appears only during the initial visual response, but the modulation of LGN reappears later in the response, suggesting separate early and late sources of attentional modulation in LGN.
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Cholinergic suppression specific to intrinsic not afferent fiber synapses in rat piriform (olfactory) cortex
Article
  • Jun 1992
1. Differences in the cholinergic suppression of afferent and intrinsic fiber synaptic transmission were studied in the rat piriform cortex. Extracellular and intracellular recording techniques were applied in an in vitro transverse slice preparation. Afferent and intrinsic fiber systems were differentially stimulated with electrodes placed in layer Ia or layer Ib, respectively. Synaptic responses were monitored in the presence of cholinergic agonists and antagonists. 2. Afferent and intrinsic fiber synaptic potentials measured extracellularly showed large differences in sensitivity to micromolar concentrations of the cholinergic agonists carbachol or (+/-)-muscarine, or to acetylcholine combined with neostigmine. Intrinsic fiber synaptic responses in layer Ib were strongly reduced in the presence of cholinergic agonists, whereas afferent fiber synaptic responses in layer Ia were largely unaffected. At a concentration of 100 microM, all three agonists caused a greater than 60% decrease in the height of the intrinsic fiber synaptic potential but less than 15% reduction in the afferent fiber synaptic potential. 3. Intracellular recordings confirmed that the cholinergic agonist carbachol selectively suppresses intrinsic fiber synaptic potentials but not afferent fiber synaptic potentials recorded from the same pyramidal cell. 4. Dose-response curves to carbachol were obtained for both fiber systems using extracellular recording of evoked field potentials. Carbachol suppressed intrinsic fiber synaptic potentials with a coefficient of dissociation (KD) estimated at 2.9 microM and an inhibitory concentration for 50% response estimated at 6.6 microM. 5. Carbachol produced a proportionately greater suppression of the first pulse than the second pulse of a pulse pair. This increase in the level of facilitation accompanying suppression suggests a presynaptic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
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Cholinergic nucleus basalis neurons may influence the cortex via the thalamus
Article
  • Mar 1987
  • NEUROSCI LETT
The cholinergic neurons of the nucleus basalis of Meynert have been shown to provide the major cholinergic innervation of the cerebral cortex through which cholinergic transmission may modulate cortical activity. This study describes a projection from the cholinergic and non-cholinergic neurons of the nucleus basalis to the reticular nucleus of the thalamus, and a projection from the brainstem cholinergic neurons to the reticular nucleus as well as to other thalamic nuclei. The projection from the nucleus basalis to the reticular nucleus, which itself is synaptically interconnected with other thalamic nuclei, may provide an additional pathway for the modulation of cortical activity by the cholinergic basal forebrain and brainstem groups.
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Cholinergic modulation of the functional organization of the cat visual cortex
Article
  • Jan 1984
  • BRAIN RES
The cortex receives a cholinergic input which is considered to be involved in mediating the effects of arousal. The experiments reported here have examined the nature of the cholinergic influence on the neuronal organization of the cat visual cortex. Out of 83 cells studied, 92% exhibited a modification in their visual response properties during the iontophoretic application of ACh. These comprised 61% in which responses were facilitated and 31% in which responses were depressed. The facilitatory effects were associated with a striking increase in stimulus specific responses without any concomitant loss in the selectivity. This comment applied equally to orientation and direction selectivity. It is argued that the facilitatory action of ACh on stimulus specific responses is consistent with a modulation of potassium conductance and most probably the conductance associated with a voltage dependent channel. We found no evidence to support the view that the facilitatory action involved disinhibition; the action of bicuculline, which blocks inhibitory influences in the visual cortex, was quite distinct to that of ACh. The facilitatory and depressive effects of ACh did not show any correlation with the simple-complex classification of cells or any other obvious parameter of receptive field organization, but there was a correlation with cortical lamination. Cells facilitated by ACh were found in all cortical laminae, but those depressed by ACh were found in laminae III and IV.
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