Synaptic vesicle dynamics govern the release of neurotransmitter and regulation of synaptic vesicle dynamics will control synaptic function and short-term plasticity. Here, we investigate the function of the a2d subunit of voltage sensitive calcium channels and propose that it is a powerful regulator of synaptic vesicle dynamics. Therefore, altering a2d subunit function via pharmaceutical intervention may slow synaptic vesicle dynamics and reduce neurotransmitter release and enhance short-term depression. a2d ligands are such pharmaceutical intervention and are potent analgesic and anticonvulsant drugs. Thus scrutinizing the function of the a2d subunit will lead to new insights about the regulation of synaptic vesicle dynamics. Furthermore, exploiting the signaling pathway downstream of the a2d subunit may lead to promising, future targets for the development of advanced anticonvulsant and analgesic drugs.

Public Health Relevance

The efficacy of synaptic connections governs neuronal activity within the central nervous system. In patients with epilepsy or chronic pain neuronal activity reaches pathological high levels and a subtle reduction of synaptic efficacy may prevent seizures and alleviate pain. In this application, we scrutinize whether limiting the availability of neurotransmitter containing synaptic vesicles can be exploited to reduce synaptic efficacy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Enhancement Award (SC1)
Project #
5SC1NS077776-04
Application #
8670038
Study Section
Special Emphasis Panel (ZGM1-MBRS-X (NP))
Program Officer
Talley, Edmund M
Project Start
2011-09-01
Project End
2015-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
4
Fiscal Year
2014
Total Cost
$291,651
Indirect Cost
$68,901
Name
Universidad Central Del Caribe
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
090534694
City
Bayamon
State
PR
Country
United States
Zip Code
00960
Schikorski, Thomas (2014) Readily releasable vesicles recycle at the active zone of hippocampal synapses. Proc Natl Acad Sci U S A 111:5415-20