Distinct roles of AMPA, NMDA, and GABA kinetics in shaping macroscopic cortical dynamics.

Abstract

The balance between excitation and inhibition (E-I balance) regulates transitions between asynchronous irregular firing and coherent oscillations in cortical networks; yet, the specific contributions of distinct synaptic timescales remain poorly understood. While excitatory transmission is mediated by both fast α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and slow N-methyl-D-aspartate (NMDA) receptors, most theoretical models lump these into a single effective conductance, obscuring their distinct roles in shaping network dynamics. Here, we investigate this problem using a sparsely connected network of quadratic integrate-and-fire neurons incorporating physiologically realistic AMPA, NMDA, and Gamma-aminobutyric acid (GABA) kinetics. By deriving an exact low-dimensional mean-field reduction, we systematically explore the bifurcation structure of the system. We find that shortening the NMDA decay time can lead to transitions between foci and limit cycles, and abrupt alpha-to-gamma frequency jumps reminiscent of epileptic transitions. Conversely, prolonging NMDA or AMPA decay times stabilizes low-rate asynchronous irregular firing activity through enhanced shunting effects, while GABAergic decay kinetics exert only marginal influence in the thermodynamic limit. Furthermore, increasing external drive suppresses oscillations, shifting the network toward the high-rate asynchronous regime associated with heightened arousal. These results demonstrate that glutamatergic receptor kinetics are critical control parameters for E-I balance, providing a mechanistic framework for understanding how synaptic anomalies drive pathological rhythmopathies, such as epilepsy and providing insights into the maintenance of cognitive states.