The Role of Inhibitory Interneurons in Circuit Assembly and Refinement Across Sensory Cortices

Abstract

Sensory information is transduced into electrical signals in the periphery by specialized sensory organs, which relay this information to the thalamus and subsequently to cortical primary sensory areas. In the cortex, microcircuits constituted by interconnected pyramidal cells and inhibitory interneurons, distributed throughout the cortical column, form the basic processing units of sensory information underlying sensation. In the mouse, these circuits mature shortly after birth. In the first postnatal week cortical activity is characterized by highly synchronized spontaneous activity. While by the second postnatal week, spontaneous activity desynchronizes and sensory influx increases drastically upon eye opening, as well as with the onset of hearing and active whisking. This influx of sensory stimuli is fundamental for the maturation of functional properties and connectivity in neurons allocated to sensory cortices. In the subsequent developmental period, spanning the first five postnatal weeks, sensory circuits are malleable in response to sensory stimulation in the so-called critical periods. During these critical periods, which vary in timing and duration across sensory areas, perturbations in sensory experience can alter cortical connectivity, leading to long-lasting modifications in sensory processing. The recent advent of intersectional genetics, in vivo calcium imaging and single cell transcriptomics has aided the identification of circuit components in emergent networks. Multiple studies in recent years have sought a better understanding of how genetically-defined neuronal subtypes regulate circuit plasticity and maturation during development. In this review, we discuss the current literature focused on postnatal development and critical periods in the primary auditory (A1), visual (V1), and somatosensory (S1) cortices. We compare the developmental trajectory among the three sensory areas with a particular emphasis on interneuron function and the role of inhibitory circuits in cortical development and function.

Temporal manipulation of the Scn1a gene reveals its essential role in adult brain function

“… 32-35 Later during adolescence, the major inhibitory interneuron subtypes develop including PV, somatostatin (SST) and calretinin (CR) and inhibitory neurotransmission becomes more prominent, helping to refine the dynamics of pyramidal cell activity. 29 , 30 Thus, the balance of excitatory to inhibitory inputs on pyramidal neurons progresses towards higher levels of inhibition. 36 Similarly, in the development of cortico-hippocampal circuit, in the first postnatal weeks we assist to a progressive sparsification of dentate gyrus neuron firing, together with an increased temporal precision of granule cell activation.…”

Experience dependence of alpha rhythms and neural dynamics in mouse visual cortex

“…This may reflect the persistent drive of diffused light through the closed eyelids, which reduced high-contrast specificity of the wideband oscillations as well as increased transmission through thalamus and cortex. Both enucleation and suture disrupt the development of cortical inhibitory circuits (Ferrer and De Marco Garcia, N V, 2022), so the normal-to-enhanced power of wideband gamma dependent on intracortical inhibition is unexpected. It is likely that homeostatic balancing of excitatory and inhibitory synapses can compensate to allow interneurons to synchronize the network with reduced absolute inhibition.…”

“…Lid-suture likely increases visual sensitivity, as these animals have larger and more prevalent gamma oscillations despite lowered luminance levels as a result of the closed eyelids. This may be the result of decreased inhibition as both enucleation and suture disrupt the development of cortical inhibitory circuits (Ossandón et al, 2023; Ferrer and De Marco Garcia, 2022).…”

The development of bi‐directionally coupled self‐organizing neurovascular networks captures orientation‐selective neural and hemodynamic cortical responses

“…It is important to note that “excitatory” and “inhibitory” only refer to the impact of the unit on the lateral connectivity – either increasing or reducing the local activity, respectively – and are not meant to reflect different classes of biological neurons. Excitatory and inhibitory neurons have many different characteristics, and even different subtypes of inhibitory neurons can play very different roles in neural circuitry (Ferrer & De Marco García, 2022; Keller & Martin, 2015; Schneider‐Mizell et al, 2023; Song et al, 2020; Wagatsuma et al, 2022). Additionally, there are critical differences in neuronal sub‐type specific interactions with the vasculature (Wu et al, 2022).…”