Cholinergic Inhibition of Neocortical Pyramidal Neurons

Gulledge, Allan T.; Stuart, Gregory J

doi:10.1523/jneurosci.2697-05.2005

Cited by 171 publications

(148 citation statements)

References 55 publications

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“…This excludes the possibility that the persistent hyperpolarization is an artifact resulting from our experimental conditions. Moreover, in contrast to earlier studies (10,12), our results demonstrate that puff applications of ACH induce a monophasic depolarization in the majority of L2/3 and L5 PCs and a biphasic response only in a fraction of these neurons. It is likely that the indirect hyperpolarizing transient due to excitation of GABAergic interneurons in (12) depends on high concentrations of ACH (10 mM), and that the hyperpolarizing transient induced by direct activation of K Ca channels in (10) depends on preceding spiking activity (30).…”

Section: Discussioncontrasting

confidence: 99%

“…The ACH-induced persistent hyperpolarization described here is in marked contrast to the ACH-induced persistent depolarization previously demonstrated in identified neocortical PCs (9)(10)(11)(12). Therefore, it is likely that this type of response is a unique feature of L4-SNs.…”

Section: Resultscontrasting

confidence: 90%

“…The presence of a different mACHR subtype in L4-SNs than in the L2/3 and L5 PCs further supports the idea of a layerspecific effect of ACH. Previous studies showed that both the persistent depolarization and transient hyperpolarization in neocortical PCs were mediated by M 1 Rs (10,12,39). Our finding of M 4 Rs in L4-SNs is consistent with immunohistochemical (40) and in situ hybridization (41) studies showing that M 4 Rs are mostly found in L4 while M 1 Rs are mostly found in the other layers.…”

Section: Discussionsupporting

confidence: 91%

“…In previous studies in rodents, a persistent hyperpolarization in response to ACH has only been observed in a few subpopulations of inhibitory neurons of the hippocampus and neocortex (30)(31)(32) as well as in extracortical regions of the CNS or in the PNS (33)(34)(35). In the neocortex, application of ACH has been reported to invariably induce a persistent depolarization in identified excitatory neurons (9)(10)(11)(12).…”

Section: Discussionmentioning

confidence: 94%

“…These studies showed that ACH invariably induces a persistent increase in the excitability of pyramidal cells (PCs) through activation of postsynaptic muscarinic ACH receptors (mACHRs) (9)(10)(11)(12), even though in 2 particular experimental conditions (10,12) puff applications of ACH evoke a transient (Ϸ1 s) hyperpolarization preceding or superimposed on a persistent depolarization. Neocortical nicotinic ACHRs mainly found on axon terminals have been shown to enhance synaptic transmission (13).…”

mentioning

confidence: 99%

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Cholinergic filtering in the recurrent excitatory microcircuit of cortical layer 4

Eggermann

Feldmeyer

2009

Proc. Natl. Acad. Sci. U.S.A.

101

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Neocortical acetylcholine (ACH) release is known to enhance signal processing by increasing the amplitude and signal-to-noise ratio (SNR) of sensory responses. It is widely accepted that the larger sensory responses are caused by a persistent increase in the excitability of all cortical excitatory neurons. Here, contrary to this concept, we show that ACH persistently inhibits layer 4 (L4) spiny neurons, the main targets of thalamocortical inputs. Using whole-cell recordings in slices of rat primary somatosensory cortex, we demonstrate that this inhibition is specific to L4 and contrasts with the ACH-induced persistent excitation of pyramidal cells in L2/3 and L5. We find that this inhibition is induced by postsynaptic M 4 -muscarinic ACH receptors and is mediated by the opening of inwardly rectifying potassium (K ir ) channels. Pair recordings of L4 spiny neurons show that ACH reduces synaptic release in the L4 recurrent microcircuit. We conclude that ACH has a differential layer-specific effect that results in a filtering of weak sensory inputs in the L4 recurrent excitatory microcircuit and a subsequent amplification of relevant inputs in L2/3 and L5 excitatory microcircuits. This layer-specific effect may contribute to improve cortical SNR.

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Section: Discussioncontrasting

confidence: 99%

Section: Resultscontrasting

confidence: 90%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

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Cholinergic filtering in the recurrent excitatory microcircuit of cortical layer 4

Eggermann

Feldmeyer

2009

Proc. Natl. Acad. Sci. U.S.A.

101

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Phasic cholinergic signaling in the hippocampus: Functional homology with the neocortex?

Gulledge

Kawaguchi

2007

Hippocampus

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Acetylcholine (ACh) acts as a neurotransmitter in both the hippocampus and neocortex to facilitate learning, memory, and cognitive function. Here we show that transient muscarinic ACh receptor (mAChR) activation inhibits action potential generation in CA1, but not in CA3, pyramidal neurons via activation of an SK-type calcium-activated potassium conductance. Hyperpolarizing responses generated by focal ACh application near the somata of CA1 pyramidal neurons were blocked by atropine or the M1-like mAChR antagonist pirenzepine, but not by the M2-like mAChR antagonist methoctramine. Inhibitory cholinergic responses required intracellular calcium signaling, as evidenced by their sensitivity to depletion of internal calcium stores or internal calcium chelation. Cholinergic inhibition did not require GABAergic synaptic transmission, but was blocked by apamin, an SK channel antagonist. In contrast to inhibitory effects in CA1 neurons, ACh was primarily depolarizing, and enhanced action potential firing in CA3 pyramidal neurons. These results, when combined with recent data in neocortical neurons, suggest a functional homology in phasic cholinergic signaling in the hippocampus and neocortex whereby ACh preferentially inhibits those neurons in the lower cortical layers (CA1 and layer 5 neurons) that provide the majority of extracortical efferent projections.

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Dendritic EGFP‐STIM1 activation after type I metabotropic glutamate and muscarinic acetylcholine receptor stimulation in hippocampal neuron

Krogh

Toresson

2011

J of Neuroscience Research

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Several signaling pathways in neurons engage the endoplasmic reticulum (ER) calcium store by triggering calcium release. After release, ER calcium levels must be restored. In many non-neuronal cell types, this is mediated by store-operated calcium entry (SOCE), a cellular homeostatic mechanism that activates specialized store-operated calcium channels (SOC). Although much evidence supports the existence of SOCE in neurons, its importance has been difficult to determine because of the abundance of calcium channels expressed and the lack of SOC-specific pharmacological agents. We have explored the function of the SOCE-inducing protein STIM1 in neurons. In EGFP-STIM1-expressing hippocampal neurons, the sarco- and endoplasmic reticulum calcium ATPase (SERCA) inhibitor thapsigargin caused rapid aggregation (i.e., activation) of STIM1 in soma and dendrites. Upon STIM1 activation by thapsigargin, a dramatic reduction in STIM1 mobility was detected by fluorescence recovery after photobleaching (FRAP). By triggering release of ER calcium with 3,5-dihydroxyphenylglycine (DHPG) or carbachol (Cch), agonists of type I metabotropic glutamate receptors (mGluR) and muscarinic acetylcholine receptors (mAChR), respectively, STIM1 was activated, and calcium entry (likely to represent SOCE) occurred in dendrites. It is therefore possible that neuronal SOCE is activated by physiological stimuli, some of which may alter the postsynaptic calcium signaling properties.

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Cholinergic Inhibition of Neocortical Pyramidal Neurons

Cited by 171 publications

References 55 publications

Cholinergic filtering in the recurrent excitatory microcircuit of cortical layer 4

Cholinergic filtering in the recurrent excitatory microcircuit of cortical layer 4

Phasic cholinergic signaling in the hippocampus: Functional homology with the neocortex?

Dendritic EGFP‐STIM1 activation after type I metabotropic glutamate and muscarinic acetylcholine receptor stimulation in hippocampal neuron

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