A role for gliotransmission in delayed neuronal death

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DESCRIPTION (provided by applicant): Astrocytes release a number of gliotransmitters which modulate synaptic plasticity and neuronal excitability. Astrocytes activate neuronal NMDA receptors by releasing glutamate and D-serine in a calcium dependent fashion. Hyper-stimulation of the NMDA receptor results in excitotoxic neuronal death. Preliminary evidence indicates that status epilepticus (SE) results in a prolonged increase in astrocytic calcium excitability that is temporally correlated with SE-induced neuronal death. I will use electrophysiological techniques along with two-photon imaging to ask whether gliotransmission causes SE-induces neuronal death by stimulating the NMDA receptor. This will be facilitated by the use of astrocyte-specific inducible transgenic where inositol 1,4,5 triphosphate-dependent calcium signaling has been targeted. The role of astrocytes in brain disorders is poorly understood. The research propsed herein will give more insight to the role of astrocytes in epilepsy, and potentially, to many other brain disorders including Alzheimer's disease, Parkinson's disease, depression and schizophrenia. This knowledge will allow the scientific community to design novel treatments to target these disorders.