A prominent feature of the aging brain is that its processing speed slows down, which is reflected as an increase in behavioral reaction time and within-individual variability in processing speed. The underlying neural mechanism for these changes remains unclear. Since reaction time is commonly used as the dependent behavioral readout in attention tasks, the slowing of reaction time in the aging brain can reflect a general decline in attention. The goal of this research is to test the hypothesis that non-cholinergic (non-ACh) basal forebrain (BF) neurons serve as a generic mechanism of attention to speed up processing speed and reduce reaction time. Further, we test whether the decline of processing speed in reaction results from an impaired cortico-basal forebrain interaction. BF is one of the largest neuromodulatory systems, which projects extensively to the entirely cerebral cortex. While BF is mostly known for providing the sole source of cholinergic modulation of cortical networks, recent anatomical studies in rats, cats and primates have established that the majority of the BF corticopetal projections are in fact non-ACh neurons, consisting of mostly GABAergic neurons and a smaller subset of glutamatergic neurons. My recent studies support an important role of non-ACh neurons in the context of attention: I discovered that a homogeneous group of non-ACh BF neurons are robustly activated when animals pay attention to motivationally salient cues that predict reward or punishment. In turn, the activation of these neurons, in the form of ensemble bursting, is associated with improved behavioral performance and transient excitation of cortical activity, both hallmarks of top-down attention. These findings support that the activation of non-ACh BF neurons can enhance cortical processing, leading to faster processing and reduced reaction time. Substantial effort during the current reporting period has focused predominantly on start-up activities, including lab set up, staff recruitment and training, animal acquisition and the development of behavioral paradigms. A nose poke based tone detection task is being developed to accurately assess behavioral reaction time. Young and old F344BNF1 rats are being trained to assess their behavioral reaction time in relation to BF neuronal activity.
