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

Abstract

Graphical Abstract Highlights d Distinct circuits in upper and lower layer 6a distinguish two functional sublayers d Interlaminar inhibitory neurons reside in a specialized sublayer in upper layer 6a d Interlaminar interneurons integrate both local and thalamic inputs d Interlaminar inhibitory projections contribute to the canonical cortical microcircuit SUMMARYThe 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.

Interhemispheric Callosal Projections Sharpen Frequency Tuning and Enforce Response Fidelity in Primary Auditory Cortex

“…This suggests that much of the tonic activity of deep layer PV cells is driven by interhemispheric input. Deep layer interneurons have recently been shown to project axons through all cortical layers toward the pia (Bortone et al, 2014;Frandolig et al, 2019). It is possible that interlaminar projections from deep layer PV interneurons mediate the indirect network effects underlying principal cell excitation following withdrawal of callosal input.…”

Robust effects of corticothalamic feedback and behavioral state on movie responses in mouse dLGN

“…Even within the population of L6 CT pyramidal cells, there are at least 2 subtypes defined by morphology [87][88][89], 3 subtypes defined by electrophysiology and morphology [89], and and carnivores, where feedforward processing along the retino-geniculo-cortical pathway occurs in functionally segregated, parallel pathways, CT feedback circuits seem to mimic this organization, both in terms of morphology [90,91] and function [92] [99]. Instead, a crucial element to produce gain modulations seems to be changes in the level of synaptically driven V m fluctuations, often called "synaptic noise" [100][101][102].…”

Layer 6b Is Driven by Intracortical Long-Range Projection Neurons

“…Nevertheless, previous work has shown that L6 Ntsr1 neurons receive a large portion of their anatomical input from long-range projection neurons (Vé lez-Fort et al, 2014). L6 Ntsr1 neurons also receive less thalamic input, especially deep Ntsr1 neurons (Frandolig et al, 2019), compared with intracortical L6a neurons and L4 neurons (Crandall et al, 2017;Wang et al, 2013). In light of these comparisons, the overlap between Ntsr1 and Drd1 L6b neurons is unknown but may be an important consideration.…”