Sleep and Memory Across the Estrous Cycle
Females are more than twice as likely to develop a mental health disorder (e.g. PTSD) than males, yet there is a giant deficit of research in females. Our lab is interested in researching the physiological mechanisms , specifically in regards to sleep, that account for this vulnerability. Sleep characteristics, such as sleep architecture and sleep quality, fluctuate throughout the estrous cycle, and ultimately influence the consolidation and plasticity of memories. We are interested at looking at a special time during sleep, REM sleep, for an explanation of these sex differences.
Sleep and Insight
Despite sleep being nearly ubiquitous in the animal kingdom, it remains poorly understood. There are many anecdotal stories highlighting sleep and dreaming as playing a major role in the generation of eureka moments. Some of the most famous of these being the arrangement of the periodic table, the scientific method, and the discovery that neurons communicate with chemical transmission. In the Poe lab, we use an interdisciplinary approach to tackle the question of how sleep facilitates fain of insight. We are developing a novel behavioral task, the Insight Maze, to test our hypotheses.
Propranolol
Sleep disturbance is a significant underlying factor in the development of maladaptive responses to emotionally traumatic events. Heightened sympathetic nervous system activity is a hallmark of post-traumatic stress disorder (PTSD), and sleep is known to be an important regulator of both emotion and autonomic nervous system function. Recent studies from our lab and other groups show that changes in sleep after traumatic stress exposure can predict PTSD symptomatology. We have also found that an activity increase in the sympathetic locus coeruleus during sleep causes the same sleep changes as trauma-exposed animals who display PTSD symptoms. The locus coeruleus fires at all times except throughout REM sleep and for seconds prior to each sleep spindle in non-REM sleep. Thus, noradrenergic receptors are occupied except during these times. Beta adrenergic receptors enhance long-term potentiation and prevent its reversal, depotentiation. Depotentiation is necessary for the consolidation of reversal learning including the extinction of fear that allows resilience after trauma. We hypothesize that continuous activity in the noradrenergic locus coeruleus during sleep leads to PTSD by preventing the depotentiation-dependent consolidation of extinction (e.g. safety) contexts. We are testing whether the intervention of blocking beta noradrenergic receptors during sleep after extinction training, using propranolol (40 mg/kg) would confer resilience to trauma-exposed animals. As the critical window for memory consolidation is 4-5 hours after learning, we delayed propranolol injection in a control group by 4 hours. We found that immediate post-extinction propranolol enhanced fear extinction recall, reducing freezing to levels shown in non-trauma-exposed animals, whereas later propranolol injection impaired extinction memory such that freezing levels were similar to those of untreated trauma-exposed animals. Thus, blockade of noradrenergic pathways in the immediate period following extinction training enhances extinction memory consolidation in trauma-exposed groups, presumably by supporting sleep-dependent depotentiation of fear circuits which requires low noradrenergic tone.
Malapropos Norepinephrine
The locus coeruleus (LC) is the primary source of noradrenergic input to the forebrain, promoting long-term potentiation to expedite learning. During sleep, the LC is silent, allowing memories to be restructured. After a task that required memory restructuring, we amplified noradrenaline during sleep, disrupting consolidation, altering spike firing in the hippocampus, and reducing reliance on the hippocampus.
Creating a Fully Automatic Sleep Scorer Program Using Gamma Power
The Poe Lab, among many other sleep researchers, has relied heavily on a process called sleep scoring. Sleep scoring is the process of manually identifying sleep states based on the visualization of electrophysiological features of electroencephalographic (EEG) or local field potential (LFP) recordings in rats and mice. However, this is traditionally a laborious and time-intensive technique, and we hope to abolish the need for manual scoring by creating a fully automated sleep scorer program that does not rely on training data. We are utilizing power spectra in the olfactory bulb and in the hippocampus, which can be used to automatically identify and characterize sleep states without the need for manual identification.
Sleep Modulation to Improve Learning and Memory
This project investigates mechanisms of memory consolidation during human sleep and is aimed at aiding in the development of new technologies to improve learning, memory, and the generation of insights through sleep.