Spatiotemporal differences of GABAergic polarization and shunting during dendritic integration

• DOI: 10.1101/2025.04.05.647352
• Publication Date: 2025-04-07T08:53:15Z
• Authors: Yulia Dembitskaya; Artem Kirsanov; Yu-Wei Wu; Alexey Brazhe; Alexey Semyanov

AbstractIn the adult brain, GABA exerts either depolarizing or hyperpolarizing effects on neuronal membranes, depending on neuron type, subcellular location, and neuronal activity. Depolarizing GABA typically inhibits neurons through shunting, which is characterized by increased membrane conductance upon GABAAreceptor activation; however, it can also excite neurons by recruiting voltage-dependent conductances. The net influence of these opposing actions of depolarizing GABA on glutamatergic synaptic inputs remains incompletely understood. Here, we examined the spatiotemporal characteristics of membrane polarization and shunting mediated by GABAAreceptors and assessed their functional impact on the integration of GABAergic and glutamatergic inputs along dendrites. Using whole-cell current-clamp recordings in CA1 pyramidal neurons and dentate gyrus granule cells (GCs) from rat hippocampal slices, we mimicked GABAergic and glutamatergic inputs with local GABA puffs and glutamate spot-uncaging, respectively. A mathematical model further quantified the relative effects of local shunting and polarization. Depolarizing GABAergic postsynaptic responses (GPSRs) exhibited biphasic actions, exerting inhibitory effects at the synapse through shunting, and excitatory effects distally, where depolarization predominated. The excitatory component also persisted longer than the shunting inhibition. In contrast, hyperpolarizing GPSRs remained consistently inhibitory across both spatial and temporal dimensions. These findings highlight the complex spatiotemporal interplay between shunting and membrane polarization mediated by GABAergic inputs, providing new insights into dendritic computation and neuronal network dynamics.