A Novel Approach to Study Coherent Gamma Band Oscillations in Hippocampal brain sections.

Gamma-band oscillations (GBOs) are generated by fast-spiking interneurons and are critical for cognitive functions. Abnormalities in GBOs are frequently observed in schizophrenia and bipolar disorder and are strongly correlated with cognitive impairment. However, the underlying mechanisms are poorly understood. Studying GBOs in ex vivo preparations is challenging due to high energy demands and the need for continuous oxygen delivery to the tissue. As a result, GBOs are typically studied in brain tissue from very young animals or in experimental setups that maximize oxygen supply but compromise spatial resolution. Thus, there is a limited understanding of how GBOs interact within and between different brain structures remains or in brain tissue from mature animals. To address these limitations, we have developed a novel approach for studying GBOs in ex vivo hippocampal slices from mature animals, utilizing 60-channel, perforated microelectrode arrays (pMEAs). pMEAs enhance oxygen delivery and increase spatial resolution in electrophysiological recordings, enabling comprehensive analyses of GBO synchronization within discrete brain structures. We found that transecting the Schaffer collaterals, a neural pathway within the hippocampus, impairs GBO coherence between CA1 and CA3 subfields. Furthermore, we validated our approach by studying GBO coherence in an Ank3 mutant mouse model exhibiting inhibitory synaptic dysfunction. We discovered that GBO coherence remains intact in the CA3 subfield of these mutant mice but is impaired within and between the CA1 subfield. Overall, our approach offers significant potential to characterize GBOs in ex vivo brain sections of animal models, enhancing our understanding of network dysfunction in psychiatric disorders. Significance Statement Synchronized brain activity is crucial for various cognitive behaviors, and abnormalities in gamma-band oscillations (GBOs) are prevalent in numerous mental health disorders. Our study presents an innovative method that utilizes microelectrode arrays to record GBOs across multiple locations within the hippocampus. This approach allows us to investigate the development of GBO coherence within and between specific subregions of the hippocampus, providing a more comprehensive understanding of how brain activity is synchronized in both healthy rodents and animal models of neurological and psychiatric diseases.