The purpose of this work is to study calcium (Ca) dynamics and plasticity at excitatory synapses made onto the smooth dendrites of a class of inhibitory interneuron, cerebellar stellate cells (SC). Because interneurons play a crucial role in regulating neuronal circuits, it is important to understand the mechanisms underlying changes in the efficacy of their excitatory synapses. We are interested in addressing the following questions. First, does synaptic activation triggers calcium rises in SC dendrites? Second, what are the Ca sources? Third, how spatially restricted are the Ca increases? What are the mechanisms for any Ca compartmentalization in dendritic regions near excitatory synapses? Fourth, does Ca rises result in longterm synaptic plasticity? Finally, can SC synapses be independently modulated? These questions will be addressed by recording synaptic currents (EPSCs) and imaging Ca transients in whole-cell, voltage-clamped SC dendrites from acute cerebellar slices. EPSCs will be evoked by extracellular stimulation of the parallel fibers (PFs). Ca transients and sources will be identified using Ca indicators and the required pharmacology. Induction of plasticity will be performed via high frequency stimulation delivered to the PFs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS049655-01
Application #
6829434
Study Section
Special Emphasis Panel (ZRG1-CDF-1 (29))
Program Officer
Talley, Edmund M
Project Start
2004-09-01
Project End
2008-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$30,631
Indirect Cost
Name
Harvard University
Department
Biology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Higley, Michael J; Soler-Llavina, Gilberto J; Sabatini, Bernardo L (2009) Cholinergic modulation of multivesicular release regulates striatal synaptic potency and integration. Nat Neurosci 12:1121-8
Carter, Adam G; Soler-Llavina, Gilberto J; Sabatini, Bernardo L (2007) Timing and location of synaptic inputs determine modes of subthreshold integration in striatal medium spiny neurons. J Neurosci 27:8967-77
Soler-Llavina, Gilberto J; Sabatini, Bernardo L (2006) Synapse-specific plasticity and compartmentalized signaling in cerebellar stellate cells. Nat Neurosci 9:798-806