Keeping Your Brain in Balance: Homeostatic Regulation of Network Function

Abstract

To perform computations with the efficiency necessary for animal survival, neocortical microcircuits must be capable of reconfiguring in response to experience, while carefully regulating excitatory and inhibitory connectivity to maintain stable function. This dynamic fine-tuning is accomplished through a rich array of cellular homeostatic plasticity mechanisms that stabilize important cellular and network features such as firing rates, information flow, and sensory tuning properties. Further, these functional network properties can be stabilized by different forms of homeostatic plasticity, including mechanisms that target excitatory or inhibitory synapses, or that regulate intrinsic neuronal excitability. Here we discuss which aspects of neocortical circuit function are under homeostatic control, how this homeostasis is realized on the cellular and molecular levels, and the pathological consequences when circuit homeostasis is impaired. A remaining challenge is to elucidate how these diverse homeostatic mechanisms cooperate within complex circuits to enable them to be both flexible and stable. Expected final online publication date for the Annual Review of Neuroscience, Volume 47 is July 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Daily light-induced transcription in visual cortex neurons drives downward Firing Rate Homeostasis and stabilizes sensory processing

“…However, while multiple genes and molecules have been implicated in regulating homeostatic forms of cellular-synaptic plasticity e.g. in cultured neurons 70 , only a subset of these molecular mechanisms were demonstrated to be experience-regulated in vivo in intact neural circuits on timescales relevant for controlling FRH, and only one these genes and molecules was shown to control FRH in single neurons in vivo in the brain (the synaptic scaffolding molecule SHANK3 is necessary for upward FRH in the developing visual cortex in response to MD 32 ). Here, we combined in one coherent experimental setting a quasi-naturalistic sensory stimulus with transcriptomic, cellular-synaptic and circuit-level analyses and with a targeted genetic manipulation in the adult cortex to demonstrate - to our knowledge for the first time - that (1) the daily appearance of light leads in PYR neurons in the adult visual cortex to a rapid increase in excitatory inputs and shift in E/I-ratio towards excitation and to a rapid concomitant increase in the activity rates of these neurons, and (2) that light-induced transcription via the early-induced TF NPAS4 subsequently promotes inhibitory inputs onto these neurons to return the E/I-ratio and neural activity rates of these neurons to their pre-stimulus levels (i.e.…”

Excitatory-Inhibitory Homeostasis and Bifurcation Control in the Wilson-Cowan Model of Cortical Dynamics

“…In this work, we apply concepts from the field of dynamical systems, such as bifurcation theory and linear stability analysis, to explore the behavior of the Wilson-Cowan model under different modes of E-I homeostasis. To do this, we gather information from the literature on the mechanisms through which cortical networks regulate their balance to June 5, 2024 18/44 maintain stable firing rates [17,18,42] and translate them to equivalent adaptations in the parameters of the Wilson-Cowan model. This approach allows for the derivation of the model parameters that allow for systems to be poised at a given target firing rate ρ under different levels of incoming input.…”

“…The precise mechanisms of E-I homeostasis can take many forms, from synaptic scaling of excitatory [19,20] and inhibitory synapses [21,22] to the plasticity of the intrinsic excitability of PY neurons [23][24][25]. In addition, the mechanisms that maintain the stability of PY firing rates have been found to contribute to the self-regulation of cortical networks toward criticality [18,26]. This is particularly relevant since E-I balance is linked to edge-of-bifurcation dynamics [26][27][28][29], which are thought to be a foundational mechanism underlying the emergence of collective dynamics, such as metastability, in the cortex [27,[30][31][32][33][34].…”

Modular Arrangement of Synaptic and Intrinsic Homeostatic Plasticity within Visual Cortical Circuits

“…Defects in homeostatic plasticity contribute to pathological changes in network function by rendering circuits unable to compensate for perturbations arising during development or experiencedependent plasticity (Ellingford et al, 2021;Nelson and Valakh, 2015;Pratt et al, 2011;Radulescu et al, 2023;Ruggiero et al, 2021;Sohal and Rubenstein, 2019;Tatavarty et al, 2020). Many network features are under homeostatic control (Wen and Turrigiano, 2024), including mean firing rates (Hengen et al, 2016(Hengen et al, , 2013, sensory tuning curves (Noda et al, 2023;Rose et al, 2016), nearness to criticality (Ma et al, 2019), and the local correlation structure (Wu et al, 2020). There is also a great diversity in the underlying cellular homeostatic plasticity mechanisms, but whether particular cellular mechanisms operate in a modular manner to regulate specific network features is still unknown (Wen and Turrigiano, 2024).…”

“…A major factor in this information gap is the lack of knowledge about the induction and expression mechanisms of IHP, and the degree to which these are shared with synaptic scaling. For example, many of the classic activity manipulations used to study homeostatic plasticity, including blockade of spiking with tetrodotoxin (TTX), disrupt multiple calcium-dependent signaling pathways in parallel (Wen and Turrigiano, 2024), and which of these is necessary to trigger IHP is unknown.…”