?I am a MD-PhD psychiatrist moving into an independent tenure-track position at the University of Michigan. and I will now start an independent position at the University of Michigan Department of Psychiatry. My doctoral work was in the study of neocortical microcircuit activity using two-photon calcium imaging. To gain tools to study neuronal activity in the naturally behaving animal I devoted my fellowship to training with Dr. Gyorgy Buzsaki at New York University. With Dr. Buzsaki I have mastered many aspects of silicon probe recording in rats and am now using optogenetics to study the basic neuroscience of sleep. Sleep is crucial to normal brain function and also plays a role in many neuropsychiatric diseases including depression and seizure disorders. Perhaps indicative of a more precise role for sleep: decades of research show that learning is enhanced by post-learning sleep. By contrast, other work shows that sleep homeostatically downregulates neuronal and synaptic activity. How the homeostatic role for sleep and the memory consolidation role interact is not at all clear, especially given that they make differing predictions at the level of synapses: memory consolidation predicts synaptic strengthening over sleep, homeostasis predicts synaptic weakening. This proposal aims to synthesize the memory consolidation role for sleep and the homeostatic role. My outcomes will be measured using silicon probes and my interventions will involve learning paradigms and optogenetics. My first two Aims will assess how a novel object learning paradigm prior to sleep affects how the subsequent sleep modulates neural activity.
Aim 1 will use silicon probes to assess the changes over sleep in single neuron firing and neuronal assembly behavior depending on whether neurons were subjected to a pre-sleep learning paradigm.
Aim 2 will use optogenetics to specifically study synaptic changes over sleep depending on whether there was learning prior to sleep. Synapses have been theorized to be particularly crucial in both learning and homeostasis. I will use optogenetics to precisely probe synapses originating from distal neurons, with optogenetics giving the advantage of less contaminated and more precise and revelatory stimulation paradigms than traditional electrical stimuli.
In Aim 3 I will use direct optogenetic manipulation of spike rates in small subsets of neurons during waking, rather than learning, to determine more precisely how prior activity affects subsequent sleep modulation. This final experiment will take advantage of new combined optogenetic-silicon probe tools developed in the Buzsaki Lab. I will continue to receive mentorship from Dr. Buzsaki and I will also receive local mentorship at the University of Michigan: Dr. Juan Lopez, MD will mentor me in regards to career trajectory as he is a physician scientist and Dr. Geoff Murphy, PhD is a local expert in synaptic physiology and learning and memory
Sleep plays a crucial role in proper brain function and disordered sleep has a crucial role in many diseases, but our understanding how sleep helps the brain is limited. This proposal aims to provide training to Dr. Brendon Watson to study how sleep affects the brain in a manner that captures the likely complex interplay between the duty of sleep to help us learn but also to maintain balance in the brain. This improved understanding will allow development of further experiments and will build a road towards improved therapeutics in sleep-dependent diseases such as bipolar disorder, epilepsy and major depression.
| Watson, Brendon O; Ding, Mingxin; Buzsáki, György (2018) Temporal coupling of field potentials and action potentials in the neocortex. Eur J Neurosci 48:2482-2497 |
| Watson, Brendon O (2018) Cognitive and Physiologic Impacts of the Infraslow Oscillation. Front Syst Neurosci 12:44 |
| Fitzgerald, Paul J; Watson, Brendon O (2018) Gamma oscillations as a biomarker for major depression: an emerging topic. Transl Psychiatry 8:177 |
| Hu, Shuntong; Knowlton, Robert C; Watson, Brendon O et al. (2018) Somatic Depdc5 deletion recapitulates electroclinical features of human focal cortical dysplasia type IIA. Ann Neurol 84:140-146 |
| Levenstein, Daniel; Watson, Brendon O; Rinzel, John et al. (2017) Sleep regulation of the distribution of cortical firing rates. Curr Opin Neurobiol 44:34-42 |
| Watson, Brendon O; Levenstein, Daniel; Greene, J Palmer et al. (2016) Network Homeostasis and State Dynamics of Neocortical Sleep. Neuron 90:839-52 |
| Watson, Brendon O; Buzsáki, György (2015) Sleep, Memory & Brain Rhythms. Daedalus 144:67-82 |
