Michelle C. Dumoulin, Ph.D. - US grants

DESCRIPTION (provided by applicant): The fundamental question of why sleep exists is controversial [1]. The hypothesis that sleep plays a role in neuronal plasticity has been supported by work on a canonical model of cortical plasticity, ocular dominance plasticity (ODP) in the cat [2]. In the the cat visual cortex (VI), most neurons respond equally well to either eye;however, depriving one eye of visual input (monocular deprivation, MD) early in life increases the number of cells that respond preferentially to the non-deprived eye [3, 4]. ODP induction by MD is enhanced by subsequent sleep, indicating that sleep plays a role in the consolidation of plasticity [2]. Furthermore, several proteins involved in plasticity are activated during post-MD sleep [5]. However, the roles of rapid eye movement (REM) and non-REM (NREM) sleep states in this process are not understood. These states are both characterized by unique neuromodulatory tone and ion channel activation, and may play distinct but complementary roles in plasticity [6]. Therefore, the goal of this proposal is to investigate the requirement for each sleep state (Aim 1) and the contribution of neuromodulators and ion channel activity during sleep (Aim 2) to sleep-dependent ODP consolidation. These experiments will provide insight into fundamental mechanisms underlying the development of neural circuits, as well as neocortical memory consolidation, which is thought to underlie the formation and maintenance of long-term memory [7]. To address these questions, cats will be implanted with electrodes to monitor sleep and will undergo 6 hours of MD during waking. In Aim 1, this will be followed by normal, REM-deprived, or NREM-fragmented sleep. NREM fragmentation is a control for the nonspecific effects of REM deprivation. In Aim 2, MD will be followed by sleep during which specific antagonists of neuromodulators and ion channels will be infused into V1. For both aims, two experimental approaches will be used to quantify the impact of the manipulation on ODP consolidation. First, the effects of the manipulations on neuronal activity will be assessed using optical imaging of intrinsic cortical signals and single unit recording. Second, the effect of the manipulation on the activation of plasticity-related proteins will be quantified using Western blot analysis and immunohistochemistry. Getting inadequate amounts of sleep is linked to many physical and mental health issues and is a major public health problem that affects today's society [8]. This research will help elucidate the impact of sleep loss during childhood on brain development, as well as demonstrating the impact on cognitive function and the formation and maintenance of memories in adults.