Cell-type-specific roles of inhibitory interneurons in the rehabilitation of auditory cortex after peripheral damage

Abstract

Peripheral sensory organ damage leads to compensatory cortical plasticity that supports a remarkable recovery of perceptual capabilities. A major knowledge gap is the lack of precise mechanisms that explain how this plasticity is implemented and distributed over a diverse collection of excitatory and inhibitory cortical neurons. Here, we explored these mechanisms in mouse A1. After peripheral damage, we found recovered sound-evoked activity of excitatory principal neurons (PNs) and parvalbumin (PVs) interneurons (INs), reduced activity in somatostatin-INs (SOMs), and recovered activity in vasoactive intestinal peptide-INs (VIPs). Given the sequentially organized cortical network where VIPs inhibit INs, SOMs inhibit PVs and PNs, and PVs inhibit PNs, our results suggest that PVs contribute to PN stability, SOMs allow for increased PN and PV activity, and VIPs enable the PN and PV recovery by inhibiting SOMs. These results highlight a strategic, cooperative, and cell-type-specific plasticity program that restores cortical sound processing after peripheral damage.

Untangling stability and gain modulation in cortical circuits with multiple interneuron classes

“…In recent years, computational studies have used circuit models with multiple inhibitory neuron types to study distinct roles of inhibitory neurons like effects on network oscillations (Ter Wal and Tiesinga, 2021; Veit et al, 2023), circuit modulation e.g. via locomotion or attention (Dipoppa et al, 2018; Myers-Joseph et al, 2023; Poort et al, 2022), network stabilization (del Molino et al, 2017; Kumar et al, 2023; Litwin-Kumar et al, 2016; Palmigiano et al, 2023), and many more (Aponte et al, 2021; Hertäg and Sprekeler, 2019; Keijser and Sprekeler, 2022; Pedrosa and Clopath, 2020; Richter and Gjorgjieva, 2022; Sadeh et al, 2017; Waitzmann et al, 2024; Wilmes and Clopath, 2019). A prominent example of the division of labor hypothesis is that PV neurons are well-positioned to provide network stability (Wang et al, 2004), allowing SOM neurons the freedom to modulate the circuit.…”

Deprivation-induced plasticity in the early central circuits of the rodent visual, auditory, and olfactory systems: a systematic review and meta-analysis of the literature

“…For example, after 1 day of monocular deprivation parvalbumin-positive GABAergic basket cells in the primary visual cortex significantly reduced their firing rate and receive less synaptic excitation, whilst pyramidal cells remained unchanged (108,109). This rapid functional reduction of inhibitory tone is also supported by structural changes (110), and similar dynamics have been described in primary auditory (111)(112)(113) and somatosensory (62,114) cortices. Interestingly, the opposite manipulation -6h sensory enrichment via whisker stimulation -has been shown to induce rapid downregulation of barrel cortex pyramidal cells' excitability (115), perhaps a neuroprotective mechanism to combat runaway excitation.…”

A Recurrent Neural Network for Rhythmic Timing

“…This architecture is consistent with previous experimental findings in other brain areas such as the visual cortex 26 and auditory cortex 27 , where parvalbumin-expressing (PV+) inhibitory interneurons pair up with co-tuned excitatory cells as well as with somatostatin (SOM) interneurons. Oscillations are among the growing evidence for functional importance of such canonical circuitry 28,29 . A model of gamma oscillations in visual cortex is based on strong E-I balance based on PV+ inhibitory interneurons with somatostatin (SOM) interneurons playing a critical role in producing the oscillations 30 – albeit this is for higher frequency oscillations than considered here.…”