Desynchronization of Neocortical Networks by Asynchronous Release of GABA at Autaptic and Synaptic Contacts from Fast-Spiking Interneurons

Abstract

An activity-dependent long-lasting asynchronous release of GABA from identified fast-spiking inhibitory neurons in the neocortex can impair the reliability and temporal precision of activity in a cortical network.

Downregulation of Parvalbumin at Cortical GABA Synapses Reduces Network Gamma Oscillatory Activity

“…To test this hypothesis, we simulated a computational cortical circuit model to study the possible causal relationship between reduced parvalbumin and impaired gamma oscillations, which depend on and are thought to be generated by dynamic interaction between pyramidal and interneuron subpopulations (Tiesinga and Sejnowski, 2009). Consistent with recent experimental results (Manseau et al, 2010), reducing PV at GABAergic synapses in the model reduced gamma-band activity and increased asynchronous release of GABA, resulting in reduced responses to strong sensory-like stimuli and weakened transient storage of stimulus-related excitation. When both PV and GABA were reduced, the gamma-band oscillatory activity in response to stimuli was reduced, similar to what is observed in schizophrenia patients.…”

“…During such sensory or cognitive events, the firing rates of afferent neurons can increase several fold for a short time. Asynchronous release of neurotransmitter increases following intense synaptic stimulation (Goad and Stevens, 1994; Manseau et al, 2010). The synapses from interneurons with a deficit in parvalbumin may exhibit increased stimulus-induced resynchronization of GABA release if interneurons respond to sensory stimulation by increasing their firing rates (as a result of the increased activity of pyramidal cells population), which could also lead to reduced spectral power in gamma band and the reduced response to sensory stimuli.…”

Molecular Mechanisms for Synchronous, Asynchronous, and Spontaneous Neurotransmitter Release

“…This suggests that CCK interneurons are specialized to provide prolonged inhibition (117). In the cortex, high-frequency presynaptic activation of fast-spiking interneurons produces asynchronous release that lasts several seconds and that may prevent widespread synchronous firing and suppress epileptiform activity (119). …”

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

“…In some hippocampal interneurons, asynchronous vesicle fusion is the predominant form of neurotransmitter release (Lu and Trussell, 2000;Hefft and Jonas, 2005;Ali and Todorova, 2010;Daw et al, 2010). In cortical interneurons, asynchronous release may play an important role in regulating epileptoform activity (Manseau et al, 2010;Jiang et al, 2012;Medrihan et al, 2015). In excitatory synapses, asynchronous release can generate larger and prolonged postsynaptic responses and perhaps play a role in potentiation and plasticity (Iremonger and Bains, 2007;Peters et al, 2010;Rudolph et al, 2011).…”