The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia

Sci Rep. 2019 Dec 6;9(1):18525. doi: 10.1038/s41598-019-53682-5.

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.

MeSH terms

  • Computer Simulation
  • Evoked Potentials, Auditory / physiology*
  • GABAergic Neurons / metabolism
  • Gamma Rhythm / physiology
  • Humans
  • Interneurons / physiology*
  • Models, Neurological*
  • Parvalbumins / metabolism
  • Schizophrenia / physiopathology*
  • Synapses / physiology

Substances

  • Parvalbumins