Dataset Information

Cholinergic filtering in the recurrent excitatory microcircuit of cortical layer 4.

ABSTRACT: 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.

SUBMITTER: Eggermann E

PROVIDER: S-EPMC2710689 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Cholinergic filtering in the recurrent excitatory microcircuit of cortical layer 4.

Eggermann Emmanuel E Feldmeyer Dirk D

Proceedings of the National Academy of Sciences of the United States of America 20090629 28

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 prim ...[more]

PMID: 19564614

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Project description:In the neocortex, neuronal processing of sensory events is significantly influenced by context. For instance, responses in sensory cortices are suppressed to repetitive or redundant stimuli, a phenomenon termed "stimulus-specific adaptation" (SSA). However, in a context in which that same stimulus is novel, or deviates from expectations, neuronal responses are augmented. This augmentation is termed "deviance detection" (DD). This contextual modulation of neural responses is fundamental for how the brain efficiently processes the sensory world to guide immediate and future behaviors. Notably, context modulation is deficient in some neuropsychiatric disorders such as schizophrenia (SZ), as quantified by reduced "mismatch negativity" (MMN), an electroencephalography waveform reflecting a combination of SSA and DD in sensory cortex. Although the role of NMDA-receptor function and other neuromodulatory systems on MMN is established, the precise microcircuit mechanisms of MMN and its underlying components, SSA and DD, remain unknown. When coupled with animal models, the development of powerful precision neurotechnologies over the past decade carries significant promise for making new progress into understanding the neurobiology of MMN with previously unreachable spatial resolution. Currently, rodent models represent the best tool for mechanistic study due to the vast genetic tools available. While quantifying human-like MMN waveforms in rodents is not straightforward, the "oddball" paradigms used to study it in humans and its underlying subcomponents (SSA/DD) are highly translatable across species. Here we summarize efforts published so far, with a focus on cortically measured SSA and DD in animals to maintain relevance to the classically measured MMN, which has cortical origins. While mechanistic studies that measure and contrast both components are sparse, we synthesize a potential set of microcircuit mechanisms from the existing rodent, primate, and human literature. While MMN and its subcomponents likely reflect several mechanisms across multiple brain regions, understanding fundamental microcircuit mechanisms is an important step to understand MMN as a whole. We hypothesize that SSA reflects adaptations occurring at synapses along the sensory-thalamocortical pathways, while DD depends on both SSA inherited from afferent inputs and resulting disinhibition of non-adapted neurons arising from the distinct physiology and wiring properties of local interneuronal subpopulations and NMDA-receptor function.

Dataset Information

Cholinergic filtering in the recurrent excitatory microcircuit of cortical layer 4.

Publications

Cholinergic filtering in the recurrent excitatory microcircuit of cortical layer 4.

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