Abstract
Despite an increasing body of evidence demonstrating subcellular alterations in parvalbumin-positive (PV+) interneurons in schizophrenia, their functional consequences remain elusive. Since PV+ interneurons are involved in the generation of fast cortical rhythms, these changes have been hypothesized to contribute to well-established alterations of beta and gamma range oscillations in patients suffering from schizophrenia. However, the precise role of these alterations and the role of different subtypes of PV+ interneurons is still unclear. Here we used a computational model of auditory steady-state response (ASSR) deficits in schizophrenia. We investigated the differential effects of decelerated synaptic dynamics, caused by subcellular alterations at two subtypes of PV+ interneurons: basket cells and chandelier cells. Our simulations suggest that subcellular alterations at basket cell synapses rather than chandelier cell synapses are the main contributor to these deficits. Particularly, basket cells might serve as target for innovative therapeutic interventions aiming at reversing the oscillatory deficits.
Highlights
Fast-spiking (FS), PV+, γ-amino-butyric acidergic (GABAergic) interneurons seem to be a major contributor to gamma oscillations[18,19]
Based on the investigation of the GABAergic alterations, we focused on low chandelier cells (ChCs) percentages of 10% when exploring the excitatory ChC-pyramidal cells (PCs) coupling and the N-methyl-D-aspartate receptor (NMDAR) hypofunction
We explored the contribution of slower IPSC dynamics at ChC-PC synapses to gamma and beta range auditory steady-state response (ASSR) deficits in patients with schizophrenia using a model cortical network
Summary
Fast-spiking (FS), PV+, γ-amino-butyric acidergic (GABAergic) interneurons seem to be a major contributor to gamma oscillations[18,19]. While demonstrating that, in principle, increased IPSC decay times at chandelier cell synapses could result in experimentally observed ASSR deficits for patients with SCZ, Vierling-Claassen et al did not consider the relatively small number of chandelier cells compared to basket cells[43] They did not take into account potentially increased IPSC decay times at basket cell synapses, changes in excitability of interneurons due to NMDAR hypofunction and the putative excitatory effect of ChC-mediated neurotransmission. Decreased excitability of chandelier cells at low chandelier cell percentages, as a consequence of reduced, tonic NMDAergic excitation, did not produce ASSR deficits consistent with experimental observations, it hardly changed the network behaviour at all
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
