The consolidation of recent experiences into long-lasting memories is a fundamental function of the brain and essential for survival. Sleep has long been thought to be important for memory consolidation, and sleep deprivation has adverse consequences for cognitive function. Recent data suggest that sleep promotes the adaptive changes in connections between neurons which are thought to underlie memory formation. However, progress in understanding how sleep promotes these processes has been slow, due to the number and diversity of changes occurring simultaneously in the sleeping brain - including changes in neuronal firing patterns, intercellular signaling between neurons, and neuronal protein synthesis. The goal of the proposed research is to define which features of sleep are necessary and sufficient for a simple form of sleep-dependent memory consolidation - contextual fear memory. We will use recently-developed optogenetic and pharmacogenetic tools to manipulate neuronal activity in the sleeping brain in a cell type-specific manner. This will allow us to test whether features of network activity (e.g., low-frequency oscillations in hippocampal circuits) and neurotransmission (e.g., changes in noradrenaline and acetylcholine release) unique to the sleeping brain play a causal role in sleep-dependent memory formation. We will also use newly-developed molecular tools to profile active protein translation in specific cell types within the hippocampus during sleep- dependent memory consolidation. Finally, we will combine these tools to determine for the first time how sleep- associated changes in neuronal activity and neurotransmission impact intracellular processes such as protein translation in neural circuits.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
1DP2MH104119-01
Application #
8572410
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (56))
Program Officer
Vicentic, Aleksandra
Project Start
2013-09-26
Project End
2018-08-31
Budget Start
2013-09-26
Budget End
2018-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$2,332,500
Indirect Cost
$832,500
Name
University of Michigan Ann Arbor
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Clawson, Brittany C; Durkin, Jaclyn; Suresh, Aneesha K et al. (2018) Sleep Promotes, and Sleep Loss Inhibits, Selective Changes in Firing Rate, Response Properties and Functional Connectivity of Primary Visual Cortex Neurons. Front Syst Neurosci 12:40
Roach, James P; Pidde, Aleksandra; Katz, Eitan et al. (2018) Resonance with subthreshold oscillatory drive organizes activity and optimizes learning in neural networks. Proc Natl Acad Sci U S A 115:E3017-E3025
Ognjanovski, Nicolette; Broussard, Christopher; Zochowski, Michal et al. (2018) Hippocampal Network Oscillations Rescue Memory Consolidation Deficits Caused by Sleep Loss. Cereb Cortex 28:3711-3723
Delorme, James E; Kodoth, Varna; Aton, Sara J (2018) Sleep loss disrupts Arc expression in dentate gyrus neurons. Neurobiol Learn Mem :
Wu, Jiaxing; Skilling, Quinton M; Maruyama, Daniel et al. (2018) Functional network stability and average minimal distance - A framework to rapidly assess dynamics of functional network representations. J Neurosci Methods 296:69-83
Ognjanovski, Nicolette; Schaeffer, Samantha; Wu, Jiaxing et al. (2017) Erratum: Parvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation. Nat Commun 8:16120
Ognjanovski, Nicolette; Schaeffer, Samantha; Wu, Jiaxing et al. (2017) Parvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation. Nat Commun 8:15039
Puentes-Mestril, Carlos; Aton, Sara J (2017) Linking Network Activity to Synaptic Plasticity during Sleep: Hypotheses and Recent Data. Front Neural Circuits 11:61
Havekes, Robbert; Park, Alan J; Tudor, Jennifer C et al. (2016) Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1. Elife 5:
Clawson, Brittany C; Durkin, Jaclyn; Aton, Sara J (2016) Form and Function of Sleep Spindles across the Lifespan. Neural Plast 2016:6936381

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