bioRxiv preprint

Distinct nanoscale architectures of GABAergic inhibitory synapses predict diverse synaptic output

GABAergic synaptic inhibition is heterogenous across neuronal compartments, and plays a critical role in shaping local, cellular and circuit excitability. In pyramidal neurons, inhibition is mediated by GABAA receptors (GABAARs) clustered at the inhibitory postsynaptic domain (iPSD). Synaptic strength depends not only on the number of GABAARs within the iPSD, but also on their precise nanoscale organization into discrete sub-synaptic domains (SSDs). These SSDs often align with presynaptic GABA release sites to form nanocolumn structures that enhance synaptic efficacy. While nanocolumn organization is increasingly recognized as a key determinant of synaptic function, most studies of GABAergic

cell biologydrug discoveryneuroscience