GABA can depolarize immature neurons close to the action potential (AP) threshold in development and adult neurogenesis. Nevertheless, GABAergic synapses effectively inhibit AP firing in newborn granule cells of the adult hippocampus as early as 2 weeks post mitosis. Parvalbumin and dendrite-targeting somatostatin interneurons activate a5-subunit containing GABAA receptors (a5-GABAARs) in young neurons, which show a voltage dependent conductance profile with increasing conductance around the AP threshold. The present computational models show that the depolarized GABA reversal potential promotes NMDA receptor activation. However, the voltage-dependent conductance of a5-GABAARs in young neurons is crucial for inhibition of AP firing to generate balanced and sparse firing activity.
Model Type: Neuron or other electrically excitable cell
Region(s) or Organism(s): Dentate gyrus
Cell Type(s): Dentate gyrus granule GLU cell
Model Concept(s): Action Potentials; Detailed Neuronal Models; Development; Neurogenesis; Pattern Separation; Synaptic Integration
Simulation Environment: NEURON
Implementer(s): Schulz, Jan M [j.schulz at unibas.ch]; Bischofberger, Josef
References:
Lodge M, Hernandez MC, Schulz JM, Bischofberger J. (2021). Sparsification of AP firing in adult-born hippocampal granule cells via voltage-dependent a5-GABAA receptors Cell reports. 37 [PubMed]