Homeostatic regulation of neuronal firing rate is a fundamental problem faced by spiking neurons. However different neurons must regulate their firing rates around different firing rate set points and the circuit effects of cellular homeostasis are different for excitatory, inhibitory and modulatory neurons. Cell type specific biophysical and molecular mechanisms of firing rate homeostasis will be explored in transgenic mice that permit targeting of specific neocortical and modulatory cell types. Understanding how core FRSP machinery is modified and integrated with different sets of effectors in order to achieve homeostatic regulation across different cell types in a circuit is a crucial aspect of understand how FRSPs are implemented, and of understanding how their malfunction may alter circuit operation in disease.

Public Health Relevance

The ability of brain circuits to maintain stable firing rates is disrupted in a variety of developmental brain disorders, degenerative diseases and after brain damage. Subsequent compensatory changes in cellular and sjoiaptic properties can lead to epilepsy or other forms of abnormal activity. Understanding the molecular pathways by which diverse neuronal cell types regulate their firing in response to changes in activity may allow prevention of maladaptive homeostatic changes brought into play by other circuit pathologies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
1P01NS079419-01A1
Application #
8609247
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2013-09-28
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$233,387
Indirect Cost
$88,949
Name
Brandeis University
Department
Type
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
Joseph, Annelise; Turrigiano, Gina G (2017) All for One But Not One for All: Excitatory Synaptic Scaling and Intrinsic Excitability Are Coregulated by CaMKIV, Whereas Inhibitory Synaptic Scaling Is Under Independent Control. J Neurosci 37:6778-6785
Abraira, Victoria E; Kuehn, Emily D; Chirila, Anda M et al. (2017) The Cellular and Synaptic Architecture of the Mechanosensory Dorsal Horn. Cell 168:295-310.e19
Choy, Julian M C; Suzuki, Norimitsu; Shima, Yasuyuki et al. (2017) Optogenetic Mapping of Intracortical Circuits Originating from Semilunar Cells in the Piriform Cortex. Cereb Cortex 27:589-601
Cannon, Jonathan; Miller, Paul (2017) Stable Control of Firing Rate Mean and Variance by Dual Homeostatic Mechanisms. J Math Neurosci 7:1
O'Toole, Sean M; Ferrer, Monica M; Mekonnen, Jennifer et al. (2017) Dicer maintains the identity and function of proprioceptive sensory neurons. J Neurophysiol 117:1057-1069
Williams, Alex H; O'Donnell, Cian; Sejnowski, Terrence J et al. (2016) Dendritic trafficking faces physiologically critical speed-precision tradeoffs. Elife 5:
Gjorgjieva, Julijana; Drion, Guillaume; Marder, Eve (2016) Computational implications of biophysical diversity and multiple timescales in neurons and synapses for circuit performance. Curr Opin Neurobiol 37:44-52
Crittenden, Jill R; Tillberg, Paul W; Riad, Michael H et al. (2016) Striosome-dendron bouquets highlight a unique striatonigral circuit targeting dopamine-containing neurons. Proc Natl Acad Sci U S A 113:11318-11323
O'Leary, Timothy; Marder, Eve (2016) Temperature-Robust Neural Function from Activity-Dependent Ion Channel Regulation. Curr Biol 26:2935-2941
Steinmetz, Celine C; Tatavarty, Vedakumar; Sugino, Ken et al. (2016) Upregulation of ?3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway. Cell Rep 16:2711-2722

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