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The Synaptic Organization of Layer 6 Circuits Reveals Inhibition as a Major Output of a Neocortical Sublamina.

ABSTRACT: The canonical cortical microcircuit has principally been defined by interlaminar excitatory connections among the six layers of the neocortex. However, excitatory neurons in layer 6 (L6), a layer whose functional organization is poorly understood, form relatively rare synaptic connections with other cortical excitatory neurons. Here, we show that the vast majority of parvalbumin inhibitory neurons in a sublamina within L6 send axons through the cortical layers toward the pia. These interlaminar inhibitory neurons receive local synaptic inputs from both major types of L6 excitatory neurons and receive stronger input from thalamocortical afferents than do neighboring pyramidal neurons. The distribution of these interlaminar interneurons and their synaptic connectivity further support a functional subdivision within the standard six layers of the cortex. Positioned to integrate local and long-distance inputs in this sublayer, these interneurons generate an inhibitory interlaminar output. These findings call for a revision to the canonical cortical microcircuit.

SUBMITTER: Frandolig JE

PROVIDER: S-EPMC6941480 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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The Synaptic Organization of Layer 6 Circuits Reveals Inhibition as a Major Output of a Neocortical Sublamina.

Frandolig Jaclyn Ellen JE Matney Chanel Joylae CJ Lee Kihwan K Kim Juhyun J Chevée Maxime M Kim Su-Jeong SJ Bickert Aaron Andrew AA Brown Solange Pezon SP

Cell reports 20190901 12

The canonical cortical microcircuit has principally been defined by interlaminar excitatory connections among the six layers of the neocortex. However, excitatory neurons in layer 6 (L6), a layer whose functional organization is poorly understood, form relatively rare synaptic connections with other cortical excitatory neurons. Here, we show that the vast majority of parvalbumin inhibitory neurons in a sublamina within L6 send axons through the cortical layers toward the pia. These interlaminar ...[more]

PMID: 31533036

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Project description:BACKGROUND:Interferon-? (IFN-?, a type II IFN) is present in the central nervous system (CNS) under various conditions. Evidence is emerging that, in addition to its immunological role, IFN-? modulates neuronal morphology, function, and development in several brain regions. Previously, we have shown that raising levels of IFN-? (a type I IFN) lead to increased neuronal excitability of neocortical layer 5 pyramidal neurons. Because of shared non-canonical signaling pathways of both cytokines, we hypothesized a similar neocortical role of acutely applied IFN-?. METHODS:We used semi-quantitative RT-PCR, immunoblotting, and immunohistochemistry to analyze neuronal expression of IFN-? receptors and performed whole-cell patch-clamp recordings in layer 5 pyramidal neurons to investigate sub- and suprathreshold excitability, properties of hyperpolarization-activated cyclic nucleotide-gated current (Ih), and inhibitory neurotransmission under the influence of acutely applied IFN-?. RESULTS:We show that IFN-? receptors are present in the membrane of rat's neocortical layer 5 pyramidal neurons. As expected from this and the putative overlap in IFN type I and II alternative signaling pathways, IFN-? diminished Ih, mirroring the effect of type I IFNs, suggesting a likewise activation of protein kinase C (PKC). In contrast, IFN-? did neither alter subthreshold nor suprathreshold neuronal excitability, pointing to augmented inhibitory transmission by IFN-?. Indeed, IFN-? increased electrically evoked inhibitory postsynaptic currents (IPSCs) on neocortical layer 5 pyramidal neurons. Furthermore, amplitudes of spontaneous IPSCs and miniature IPSCs were elevated by IFN-?, whereas their frequency remained unchanged. CONCLUSIONS:The expression of IFN-? receptors on layer 5 neocortical pyramidal neurons together with the acute augmentation of inhibition in the neocortex by direct application of IFN-? highlights an additional interaction between the CNS and immune system. Our results strengthen our understanding of the role of IFN-? in neocortical neurotransmission and emphasize its impact beyond its immunological properties, particularly in the pathogenesis of neuropsychiatric disorders.

Dataset Information

The Synaptic Organization of Layer 6 Circuits Reveals Inhibition as a Major Output of a Neocortical Sublamina.

Publications

The Synaptic Organization of Layer 6 Circuits Reveals Inhibition as a Major Output of a Neocortical Sublamina.

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