Pre-synaptic neurological channelopathies. (360G-Wellcome-098994_Z_12_Z)

£192,126

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.

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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