Synaptic variability lowers cortical gamma oscillation power in schizophrenia

Gamma oscillation power in the prefrontal cortex (PFC) in schizophrenia can significantly decrease with greater variability in excitatory synaptic strength across parvalbumin interneurons (PVIs), together with other modest synaptic alterations in these neurons, suggests a recent study.

The authors assessed variability in excitatory synaptic strength across PVIs. They quantified the levels of vesicular glutamate transporter 1 (VGlut1) and postsynaptic density 95 (PSD95) proteins in postmortem PFC from 20 matched pairs of comparison and schizophrenia patients.

Subsequently, a computational model network was utilized to simulate how variability in excitatory synaptic strength across fast-spiking (a defining feature of PVIs) interneurons (FSIs) regulated gamma power.

Schizophrenia patients exhibited greater variability of VGlut1 and PSD95 levels at excitatory inputs across PVIs than did their comparators. Schizophrenia-related comorbid factors did not influence this alteration, which was not present in monkeys chronically exposed to antipsychotic medications and in calretinin interneurons.

The model network revealed that variability in excitatory synaptic strength across FSIs regulated gamma power by modifying network synchrony.

In addition, greater synaptic variability had a synergistic interaction with other synaptic alterations in schizophrenia (ie, fewer excitatory inputs to FSIs and lower inhibitory strength from FSIs) to substantially reduce gamma power.

“Cognitive impairments in schizophrenia are associated with lower gamma oscillation power in the PFC. Gamma power depends in part on excitatory drive to fast-spiking PVIs. Excitatory drive to cortical neurons varies in strength, which could affect how these neurons regulate network oscillations,” the authors said.