We hypothesize that the absence of NE in the forebrain during REM sleep and the spindle-rich transition to REM sleep (TR) allows for synaptic depotentiation underlying normal assimilation of new memories into the global memory network schema. Post-traumatic stress disorder is one condition associated with abnormally high noradrenergic tone, intense dreaming and intrusive memories. We hypothesize that an abnormal presence of norepinephrine (NE) during sleep prevents the important depotentiation process of normal memory consolidation and thus prevents novel memories from being integrated with familiar memories in the neocortical memory network. We will record from the hippocampus and LC simultaneously to determine whether hippocampal reactivation during non-REM sleep occurs differently in the absence of NE (i.e. during spindle production). We will examine hippocampal reactivation events for changes indicative of plasticity, like burst spike attenuation changes, Causal Entropy and Functional Clustering. We will examine spike firing patterns in relation to local electrical field potentials and expect to see familiar, already consolidated memories activated differently than novel memories as we have seen during REM sleep, and that such replay will be phase specific during non-REM sleep spindles just as they are phase specific to theta in REM sleep. We hypothesize that LC silence is necessary to generate spindles in the first place as well as for the synaptic strengthening and weakening effects of spindle-phase associated firing. To test the necessity for NE to be absent we will stimulate the LC at sub-arousal levels (~3 Hz) during sleep whenever we see spindles in the cortex or hippocampus through to the next awakening. We expect a marked reduction in the number of spindles generated, a loss of the depotentiation that hippocampal replay in non-REM sleep produces, and impaired memory consolidation especially for reversal tasks. This research will have strong implications for the development of effective strategies to selectively downscale synaptic networks reactivated during the dreaming and spindle stages of sleep the overly strong retention of which is debilitating in those unable to normalize and integrate their traumatic memories.

Public Health Relevance

Post traumatic stress disorder is associated with abnormally high noradrenergic tone, intense dreaming incorporating veridical elements of the traumatic memory and intrusive trauma recall. We hypothesize that an abnormal presence of norepinephrine (NE) from an overactive locus coeruleus (LC) during the transition to REM sleep and REM sleep states prevents the normal depotentiation processes of memory consolidation and thus prevents novel memories from being integrated with other familiar memories in the neocortical memory network. This research will look at normal LC and hippocampal activity profiles during post-learning memory consolidation and test whether an abnormal presence of NE during REM sleep and during the transition to REM (TR) prevents depotentiation necessary for reversal learning consolidation and extinction.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Vicentic, Aleksandra
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
Zip Code
Záborszky, Laszlo; Gombkoto, Peter; Varsanyi, Peter et al. (2018) Specific Basal Forebrain-Cortical Cholinergic Circuits Coordinate Cognitive Operations. J Neurosci 38:9446-9458
Poe, Gina R (2017) Sleep Is for Forgetting. J Neurosci 37:464-473
Emrick, Joshua J; Gross, Brooks A; Riley, Brett T et al. (2016) Different Simultaneous Sleep States in the Hippocampus and Neocortex. Sleep 39:2201-2209
Gross, Brooks A; Vanderheyden, William M; Urpa, Lea M et al. (2015) Stress-free automatic sleep deprivation using air puffs. J Neurosci Methods 251:83-91
Vanderheyden, William M; George, Sophie A; Urpa, Lea et al. (2015) Sleep alterations following exposure to stress predict fear-associated memory impairments in a rodent model of PTSD. Exp Brain Res 233:2335-46
Walsh, Christine M; Poe, Gina R (2012) The young and the rest-less. Sleep 35:745-6
Watts, Alain; Gritton, Howard J; Sweigart, Jamie et al. (2012) Antidepressant suppression of non-REM sleep spindles and REM sleep impairs hippocampus-dependent learning while augmenting striatum-dependent learning. J Neurosci 32:13411-20
Walsh, Christine M; Booth, Victoria; Poe, Gina R (2011) Spatial and reversal learning in the Morris water maze are largely resistant to six hours of REM sleep deprivation following training. Learn Mem 18:422-34
Mashour, George A; Lipinski, William J; Matlen, Lisa B et al. (2010) Isoflurane anesthesia does not satisfy the homeostatic need for rapid eye movement sleep. Anesth Analg 110:1283-9
Poe, Gina R; Walsh, Christine M; Bjorness, Theresa E (2010) Cognitive neuroscience of sleep. Prog Brain Res 185:1-19

Showing the most recent 10 out of 19 publications