Sleep and sleep states are fundamental not only to human life, but to every animal with a nervous system. Surprisingly, it is still not clear why they are so important. One compelling idea is that there are global shifts in the strengths of synaptic connections and excitability during sleep that act to keep synaptic function and neuronal excitability in a range where synapses and excitability of neurons can change relative to one another to allow for learning. If this does not happen, network function and behavior, whether in a worm or a human, degrade, leading ultimately to death. Such thinking about an important role of homeostatic mechanisms is moving to the fore in neuroscience, but what is needed to test hypotheses about global patterns of change in synapses and excitability is a model system and tools that allow us to monitor single synapses and neurons broadly in the living brain. We propose to develop and apply optical tools that allow us to examine patterns of scaling of synapses and excitability in the transparent zebrafish model where we can monitor these regularly and non-invasively over time during sleep and wakefulness. We will use these to directly test whether global resetting occurs during sleep. If sleep really involves such rescaling, the implications would be major, not only for a basic understanding of sleep, something that we should understand by now, but also for trying to restore functional states when sleep is impaired as a result of sleep disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
8DP1NS082098-04
Application #
8304984
Study Section
Special Emphasis Panel (ZGM1-NDPA-B (02))
Program Officer
Gnadt, James W
Project Start
2009-09-30
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$787,050
Indirect Cost
$292,050
Name
Cornell University
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Kishore, Sandeep; Fetcho, Joseph R (2013) Homeostatic regulation of dendritic dynamics in a motor map in vivo. Nat Commun 4:2086
Farrar, Matthew J; Bernstein, Ida M; Schlafer, Donald H et al. (2012) Chronic in vivo imaging in the mouse spinal cord using an implanted chamber. Nat Methods 9:297-302