Synchronizing the Neuronal Network in Schizophrenia: Investigating HCN1 Channel Dysregulation in the Prefrontal Cortex as a Biomarker and Developing a Biocompatible Piezoelectric Silk Neuromodulator.

Mental illnesses are prevalent within society yet patients are widely undiagnosed and mistreated. Within this complex branch of diseases, schizophrenia is an underrecognized disorder that affects about 1% of all adults in which patients portray behavioral and cognitive impairments. Although no comprehensive characterization of schizophrenia exists, there is a general consensus that patients have electrical dysfunction in the prefrontal cortex. The goal of the first phase was to analyze whether Hyperpolarization-activated Cyclic Nucleotide–gated (HCN) channel expression was increased in a Calcium/calmodulin-dependent protein kinase (CAMK2) knockout mouse model of schizophrenia. Fluorescence analysis of 4 CAMK2 and one wildtype mouse validated that HCN channels are upregulated in the prefrontal cortex with a high intensity of localization in dendrites. Notably, there was a statistical difference between the control and schizophrenic infralimbic regions but not between the control and schizophrenic prelimbic regions suggesting that electrical dysfunction is localized in the infralimbic prefrontal cortex and treatments should focus here. The second phase investigated resynchronizing neuronal firing as a treatment strategy for abnormal electrical firing which has proven to be effective in other neurological disorders. This involved designing a novel piezoelectric silk-based implant and optimizing electrical output with the addition of various concentrations of conductive materials- Zinc oxide and Aluminum nitride. Via ultrasound exposure, it was determined that the 2 M Zinc oxide-silk composite generated the highest electrical output. With further research and compatibility studies, this implant could rectify electrical misfiring in the infralimbic prefrontal cortex in schizophrenia.