Complementary networks of cortical somatostatin interneurons enforce layer specific control

Abstract

The connectivity patterns of excitatory and inhibitory microcircuits are fundamental to computation in the neocortex. Highly specific excitatory projections form a stereotyped microcircuit linking the six cortical layers, but it is unclear whether inhibitory circuits are structured according to a similar layer-based logic or instead wire up non-selectively across the different layers. Understanding principles of inhibitory wiring is critical, since they constrain the computational operations that cortical inhibition can perform. If subnetworks of inhibitory neurons target specific functional components of cortical circuits (e.g. cortical input and output layers), these targets could be independently modulated, enabling a richer repertoire of inhibitory computations. Here we use one and two photon optogenetic circuit mapping techniques to demonstrate that two distinct subtypes of spatially intermingled Layer 5 (L5) somatostatin (SOM) interneurons form exquisitely selective and complementary intracortical circuits. One subtype connects predominantly with L4 and L6 -the primary cortical input layers, while a second subtype connects nearly exclusively with L2/3 and L5 -the primary cortical 2 output layers. This highly specific architecture suggests that separate SOM networks could differentially modulate processing at the input and output stages of the neocortical microcircuit.

Toward an integrated classification of neuronal cell types: morphoelectric and transcriptomic characterization of individual GABAergic cortical neurons

“…The sixth met-type mapped to Sst Hpse Cbln4 and was found in L4 and upper L5; it strongly innervated L4 (with a less dominant projection to L1), and exhibited distinct electrophysiological properties including lower AP thresholds, less hyperpolarization-evoked sag, and more transient or irregular firing patterns. This met-type aligns with L5 Non-Martinotti cells in somatosensory cortex (Naka et al, 2019) that have distinct connectivity profiles compared to Martinotti neurons, though in visual cortex these neurons have much more L1 axon. The seventh met-type was composed of cells mapping to the Sst Crhr2 Efemp1, Sst Crh 4930553C11Rik, and Sst Esm1 t-types, was found in deep L5 and L6, and primarily innervated those layers with relatively few axonal projections to L1.…”

“…The axons of neurons mapping to the Sst Hpse Cbln4 t-type -one of two major Sst t-types found in L4 -innvervate L1 and, to a greater degree, L4. A dominant L4 projection appears to be a common feature of Sst Hpse Cbln4 neurons across cortical areas (Naka et al, 2019). These results reveal that Sst neurons highly respect laminar boundaries across cortex, they have clear laminar innervation preferences that differ based on their met-type and/or laminar position, and that their dominant laminar target may be a more reliable feature for distinguishing among Sst neurons than the presence or absence of axon in layer 1.…”

Phenotypic variation within and across transcriptomic cell types in mouse motor cortex

“…The Sst family is known to be transcriptomically and phenotypically (Muñoz et al, 2017;Nigro et al, 2018;Naka et al, 2019) diverse in L5. Here we also found that electrophysiological properties varied con- Figure 1, colored by the membrane time constant.…”

Distribution and strength of interlaminar synaptic connectivity in mouse primary visual cortex revealed by two-photon optogenetic stimulation

“…Such horizontal inhibition from somatostatin (Sst) interneurons shapes the receptive field properties of nearby pyramidal neurons in L2/3 of mouse visual cortex . Several patterns of vertical inhibition (mediated by translaminar inhibitory connections) have been described for Sst-interneurons (Kapfer et al, 2007;Silberberg and Markram, 2007;Jiang et al, 2015;Anastasiades et al, 2016;Naka et al, 2019) as well as parvalbumin-interneurons (Olsen et al, 2012;Bortone et al, 2014). Furthermore, subtypes of Sst-interneurons may be differentially integrated into distinct layer-specific subnetworks (Muñoz et al, 2017;Naka et al, 2019).…”

“…Several patterns of vertical inhibition (mediated by translaminar inhibitory connections) have been described for Sst-interneurons (Kapfer et al, 2007;Silberberg and Markram, 2007;Jiang et al, 2015;Anastasiades et al, 2016;Naka et al, 2019) as well as parvalbumin-interneurons (Olsen et al, 2012;Bortone et al, 2014). Furthermore, subtypes of Sst-interneurons may be differentially integrated into distinct layer-specific subnetworks (Muñoz et al, 2017;Naka et al, 2019). Although intra-and inter-laminar inhibitory inputs to L2/3 of V1 have been compared via one-photon photostimulation activation of GABAergic interneurons via either caged-glutamate (Xu et al, 2016) or channelrhodopsin-2 expression (Kätzel et al, 2011), potentially unique roles of subsets of GABAergic interneurons may be revealed by photostimulation techniques with increased genetic and spatial specificity.…”