Progressive Alignment of Inhibitory and Excitatory Delay May Drive a Rapid Developmental Switch in Cortical Network Dynamics

Abstract

Nervous system maturation occurs on multiple levels, synaptic, circuit, and network, at divergent time scales. For example, many synaptic properties mature gradually, while emergent network dynamics, as data show, change abruptly. Here, we combine experimental and theoretical approaches to investigate a sudden transition in spontaneous thalamocortical activity necessary for the development of vision. Inspired by in vivo measurements of time-scales and amplitudes of synaptic currents, we extend the Wilson and Cowan model to take into account the relative onset timing and amplitudes of inhibitory and excitatory neural population responses. We study the dynamics of this system and identify the bifurcations as the onset timescales of excitation and inhibition are varied. We focus on the specific typical developmental changes in synaptic timescales consistent with the experimental observations. These 1 findings argue that the inhibitory timing is a critical determinant of thalamocortical activity maturation; a gradual decay of the ratio of inhibitory to excitatory onset time below one drives the system through a bifurcation that leads to a sudden switch of the network spontaneous activity from high-amplitude oscillations to a non-oscillatory active state.This switch also drives a marked change to a linear network response to transient stimuli, agreeing to the in vivo observations. The switch observed in the model is representative of the sudden transition in the sensory cortical activity seen early in development. macroscopic patterns of activity, whose transitions can be abrupt (Colonnese et al. 2010; Rochefort et al. 2009; Golshani et al. 2009; Chipaux et al. 2013). An important question in development is whether such sudden "switches" in network dynamics reflect dramatic changes in the electrophysiological properties of cells or network circuits, or arise as nonlinear responses of the macroscopic activity to gradual changes in microscopic parameters. Establishing the relationship between cellular/synaptic maturation and the emergence of new activity patterns is thus a critical component for understanding how neural circuitry becomes functional. It is also important in order to predict how neurological disorders, which often cause subtle cellular and synaptic changes, might have outsize effects during the important developmental epochs when synapses and circuits are forming (Ackman and Crair 2014; Ben-Ari 2008). Delineating how slow developmental changes at the microscopic scale relate to the fast, macroscopic transitions is a challenge for experimental approaches. Inhibiting even processes deemed non-essential can have significant effects on the network dynamics, making it particularly challenging to disentangle the respective roles of the multiple synaptic and cellular changes in the rapid functional transitions. This is where modelling and mathematical analysis becomes essential. Sudden changes in the activity dynamics caused by smooth changes in the underlying parameters are I I J J J EE

Sensory Coding of Limb Kinematics in Motor Cortex across a Key Developmental Transition

“…Sparsification of cortical activity is timed contemporaneously with the sudden emergence of local cortical inhibition (Ben-Ari et al, 2007;Colonnese, 2014;Dooley and Blumberg, 2018). Moreover, recent modeling studies suggest that developmental changes to the balance of inhibitory and excitatory processes in cortex contribute to the sparsification of cortical activity at P12 (Rahmati et al, 2017;Romagnoni et al, 2020). Finally, given that inhibitory interneurons strongly modulate cortical sensory processing in adulthood (Wood et al, 2017;Azim and Seki, 2019), the development of inhibition in M1 may explain the developmental reduction in redundant tuning properties observed here at P12.…”

A developmental transition in the sensory coding of limb kinematics in primary motor cortex

“…Sparsification of cortical activity is timed contemporaneously with the sudden emergence of local cortical inhibition [4,35,36]. Moreover, recent modeling studies suggest that developmental changes to the balance of inhibitory and excitatory processes in cortex contribute to the sparsification of cortical activity at P12 [37,38]. Finally, given that inhibitory interneurons strongly modulate cortical sensory processing in adulthood [39,40], the development of inhibition in M1 may explain the developmental reduction in redundant tuning properties observed here at P12.…”

Early development of olfactory circuit function

“…It remains unclear how network-level activity remains stable during the first 2 weeks despite profound, gradual structural changes. Previous work on the developing visual system suggests that abrupt developmental changes in network-level activity patterns can result from dynamic interactions between gradually maturing circuit elements (Romagnoni et al, 2020). Abrupt changes in network-level activity patterns would ensure stable function during early developmental stages while incorporating new functionality in preparation for the next developmental stage.…”