Synaptic Variability and Cortical Gamma Oscillation Power in Schizophrenia

Area of Science:

• Neuroscience
• Psychiatry
• Computational Biology

Background:

• Cognitive impairments in schizophrenia correlate with reduced gamma oscillation power in the prefrontal cortex (PFC).
• Gamma power is influenced by the excitatory drive to fast-spiking parvalbumin interneurons (PVIs), which are crucial for regulating network oscillations.

Purpose of the Study:

• To investigate if variability in excitatory synaptic strength across PVIs contributes to diminished PFC gamma power in schizophrenia.
• To explore the relationship between synaptic strength variability and gamma power regulation in neural networks.

Main Methods:

• Quantified vesicular glutamate transporter 1 (VGlut1) and postsynaptic density 95 (PSD95) protein levels in postmortem PFC from schizophrenia and comparison subjects.
• Utilized a computational network model to simulate the impact of excitatory synaptic strength variability across fast-spiking interneurons (FSIs) on gamma power.

Main Results:

• Schizophrenia subjects exhibited greater variability in VGlut1 and PSD95 levels at excitatory inputs to PVIs compared to controls.
• This increased synaptic variability was not linked to comorbid factors or antipsychotic exposure and was specific to PVIs, not calretinin interneurons.
• Computational modeling demonstrated that increased synaptic strength variability across FSIs reduced gamma power by affecting network synchrony.

Conclusions:

• Greater variability in excitatory synaptic strength across PVIs, alongside other synaptic alterations, significantly reduces PFC gamma power in schizophrenia.
• These findings highlight synaptic plasticity and variability as key factors in the pathophysiology of schizophrenia-related cognitive deficits.