Bas Ooijman
The balance between excitatory and inhibitory (E:I) signaling is fundamental for normal brain function, ensuring stable brain activity while maintaining the flexibility required for information processing. Disruptions of E:I balance have been implicated in numerous neurological and psychiatric disorders, including autism spectrum disorders, schizophrenia, and major depressive disorder.
E:I balance is regulated at multiple spatial scales, including the synaptic level. Emerging findings highlight changes in the structure and molecular composition of these sites of information relay (i.e., synapses) across various neuropsychiatric disorders, but how such changes relate to shifts in E:I is largely unknown.
In addition, the organizational principles through which E:I balance is coordinated across different regions of the human brain remain incompletely characterized. To improve our fundamental and disease-associated understanding of these principles, I focus on defining the [1] excitatory and inhibitory nerve cell abundance and diversity, as well as the [2] spatial organization and [3] molecular composition of synapses - across various regions of the human brain of healthy individuals and those diagnosed with a psychiatric disorder.
Practically, this involves biochemical and imaging-based analyses of postmortem brain tissue from Netherlands Brain Bank (NBB) donors, as well as cell culture experiments.
Ultimately, this approach aims to facilitate the identification of novel drug targets that can effectively restore normal E:I, and thereby tackle clinical symptoms, in individuals suffering from psychiatric disorders.