Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits

Abstract

How neuronal connections are established and organized into functional networks determines brain function. In the mammalian cerebral cortex, different classes of GABAergic interneurons exhibit specific connectivity patterns that underlie their ability to shape temporal dynamics and information processing. Much progress has been made toward parsing interneuron diversity, yet the molecular mechanisms by which interneuron-specific connectivity motifs emerge remain unclear. In this study, we investigated transcriptional dynamics in different classes of interneurons during the formation of cortical inhibitory circuits in mouse. We found that whether interneurons form synapses on the dendrites, soma, or axon initial segment of pyramidal cells is determined by synaptic molecules that are expressed in a subtype-specific manner. Thus, cell-specific molecular programs that unfold during early postnatal development underlie the connectivity patterns of cortical interneurons.

COUP-TFI/Nr2f1 orchestrates intrinsic neuronal activity during cortical area patterning

“…We measured their intrinsic excitability profile in acute brain slices from Ctrl and Nr2f1cKO mouse pups during postnatal day (P)5-P8, when corticogenesis and neural migration already took place. We employed whole-cell recordings in current-clamp mode, and performed the measurements in the absence of synaptic blockers since, at this stage, the number of synaptic inputs resulted very low, in agreement with the low number of synaptic connections reported in other studies (Favuzzi et al, 2019). In order to compare electrophysiological properties of Ctrl and Nr2f1cKO neurons, we aimed to target similar populations by selecting neurons that were identified as LVPNs through post-hoc biocytin-filling, immunohistochemistry and morphological reconstruction.…”

Dscamgene triplication causes neocortical overinhibition in Down syndrome

“…Recent studies demonstrate that deleting Erbb4, a schizophrenia-associated gene, in ChCs causes a schizophrenia-like phenotype in mice, indicating a causal relationship between ChC defects and schizophrenia (52,72). In addition to ErbB4, Neuregulin 1, DOCK7, Fgf13 and L1CAM have also been found to regulate the synapse formation between ChCs and PyNs (49)(50)(51)73). In the present study, detailed investigation of the cartridge growth and synaptogenesis at single-cell resolution uncovered several interesting features of ChC development.…”

“…Each ChC innervates roughly two hundred PyNs at their axon initial segments (AIS) (46), where action potentials are generated (47,48). Second, the morphology of ChCs is relative stereotypical and reliably quantifiable (49)(50)(51)(52). We specifically label single ChCs in the neocortex by crossing Nkx2.1-CreER mouse line with the tdTomato reporter line Ai14 (53)( Figure 1A).…”

Robust perisomatic GABAergic self-innervation inhibits basket cells in the human and mouse supragranular neocortex

“…Autaptic terminals on pvBC are heavily perisomatic, whereas nonFSINs, when autapses are found in them, self-innervate their own dendrites akin to synaptic contacts made by these interneurons to other neurons (Favuzzi E et al 2019). Information on the self-innervation subcellular target motifs as well as knowledge on autaptic inhibition strength in identified neurons is critical for understanding the operation of autaptic microcircuits in individual neurons as well as in a neuronal network.…”