The proposed experiments and simulation studies investigate one of the first feasible mechanisms for memory consolidation during sleep. The results will elucidate particular roles for the Schaffer Collateral and temporo-ammonic inputs to the hippocampal CA1 region in memory processing and how NE and 5-HT gate these pathways during waking and Rapid Eye Movement (REM) sleep. During REM sleep, we have found that reactivation of hippocampal cells changes over the course of several days as the animals became familiar with an environment. Cells with place fields in an initially novel environment switch from firing near the theta rhythm peaks to firing near the theta troughs during REM, while maintaining their theta peak activity during waking exploration. Theta trough firing during REM may uniquely facilitate depotentiation of intra-hippocampal synapses which are associated with now familiar, cortically-consolidated memories and allow for learning of new information and the integration of novel information with old memories. This proposal seeks to test the role of the uniquely REM-suppressed neurotransmitters norepinephrine (NE) and serotonin (5-HT) in theta phase reversal, potentiation of TA-CA1 inputs, depotentiation of SC-CA1 synapses and hippocampus-dependent learning and memory. Specifically, experimental and modeling studies are proposed to investigate the hypothesis that the absence of NE and 5-HT during REM reactivation provides an environment wherein TA-CA1 synapses may be strengthened and SC-CA1 synapses may be weakened, thus indicating a unique role for REM sleep in learning and memory. Understanding the mechanisms underlying memory consolidation during sleep should lead to sleep-specific treatments for learning disabled persons and the elderly. The results will also indicate effects of commonly prescribed anti-depressants, such as selective noradrenergic (SNRIs) and serotonergic (SSRIs) re-uptake inhibitors, on learning and memory. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH076280-02
Application #
7113222
Study Section
Special Emphasis Panel (ZRG1-IFCN-B (50))
Program Officer
Glanzman, Dennis L
Project Start
2005-09-01
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
2
Fiscal Year
2006
Total Cost
$239,019
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Best, Janet; Diniz Behn, Cecilia; Poe, Gina R et al. (2007) Neuronal models for sleep-wake regulation and synaptic reorganization in the sleeping hippocampus. J Biol Rhythms 22:220-32
Waddell, Jack; Dzakpasu, Rhonda; Booth, Victoria et al. (2007) Causal entropies--a measure for determining changes in the temporal organization of neural systems. J Neurosci Methods 162:320-32
Booth, Victoria; Poe, Gina R (2006) Input source and strength influences overall firing phase of model hippocampal CA1 pyramidal cells during theta: relevance to REM sleep reactivation and memory consolidation. Hippocampus 16:161-73