Pre-synaptic neurological channelopathies. (360G-Wellcome-098994_Z_12_Z)
Inherited mutations of specific ion channels (channelopathies) are associated with several paroxysmal neurological disorders including migraine, epilepsy and ataxia. At a basic level, channelopathies such as Episodic Ataxia type 1 (EA1) and Familial Hemiplegic Migraine (FHM) provide unique insight into neuronal circuit development, synaptic function and neurotransmitter release. Both EA1 and FHM mouse models have shown increased neurotransmitter release compared to control mice. A potential hypo thesis to account for this is that pre-synaptic action potential shape is altered in these disorders. To test this, direct electrophysiological recording of the most prevalent pre-synaptic boutons is required, a process now possible due to the development of SICM. My aims are a) To identify synaptic boutons in hippocampal neuronal cultures and create high resolution contour images of them using SICM; b) To achieve whole cell patch and measure action potential width from synaptic boutons; c) W ork with the EA1 knock-in (KI) mice and investigate differences in presynaptic action potential width between wild-type and KI mice, and between excitatory and inhibitory synapses; d) Work with the FHM knock-in mice to ascertain whether action potential shape differs between excitatory and inhibitory synapses and explore the impact of any such differences on calcium-dependent neurotransmitter release.
Where is this data from?
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Grant Details
Amount Awarded | 192126 |
Applicant Surname | Vivekananda |
Approval Committee | Clinical Interview Committee |
Award Date | 2012-06-27T00:00:00+00:00 |
Financial Year | 2011/12 |
Grant Programme: Title | Research Training Fellowship |
Internal ID | 098994/Z/12/Z |
Lead Applicant | Dr Umesh Vivekananda |
Partnership Value | 192126 |
Planned Dates: End Date | 2015-12-31T00:00:00+00:00 |
Planned Dates: Start Date | 2013-01-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |
Sponsor(s) | Prof Dimitri Kullmann |