Executive Summary : | Age-related hearing loss affects 30-50% of individuals above 60 years of age, affecting up to 10 crores of the Indian population. There are no approved drugs for hearing loss, and research suggests maladaptive plasticity in the auditory-cognition brain regions. The basal forebrain is a critical structure in this network, with cholinergic neurons essential for auditory learning and behavior. However, the role of cholinergic and non-cholinergic subsets in modulating specific auditory cortical cell types with aging is unknown. The current proposal aims to evaluate the modulation of auditory cortical coding in both young and aged rats. The functional properties of different types of basal forebrain projections to the auditory cortex change with aging, altering the network's presynaptic and postsynaptic functions. The study will use electrophysiology, optogenetics, and molecular biology techniques to examine the activation of cholinergic neurons on specific subtypes of auditory cortical neurons in both young and aged mice. The work plan will use multiple viral vectors carrying red-shifted opsins and channelrhodopsins injected into specific CRE lines of mice. This will enable optogenetic tagging and recording paradigms. The outcome will elucidate the role of various projections from the basal forebrain in modulating the auditory cortex at a cellular level, leading to the design of therapeutics in hearing loss and neurodegenerative diseases. This study is unique as it addresses the impact of aging on cell-specific connectivity patterns in the basal forebrain-auditory cortex network globally. |