Glial regulation of neural signalling in health and disease with an emphasis on understanding its possible role in psychotic-like states (360G-Wellcome-099689_Z_12_Z)
Astrocytes respond to neurotransmitters released from neurons with a rise of [Ca2+]i. It is becoming increasingly clear that these [Ca2+]i rises can in turn evoke neurotransmitter release from astrocytes, which modulates neuronal function, and that microglial cells can regulate this signalling from astrocytes. We will use patch-clamping, calcium imaging and calcium uncaging in brain slices, to examine the following aspects of these newly discovered signalling pathways, which have been little studied and which may be relevant to understanding both the normal function of the CNS and the changes of function which lead to psychotic-like states. (1) How do the amine transmitters serotonin, dopamine and noradrenaline modulate astrocyte [Ca2+]i and thus synaptic currents in nearby neurons? (2) How do the main excitatory and inhibitory transmitters glutamate and GABA modulate astrocyte [Ca2+]i and thus synaptic currents in nearby neurons? (3) How do endocannabinoids modulate astrocyte [Ca2+]i and thus synaptic currents in nearby neurons? (4) How do agents known to induce psychotic-like states, such as amphetamine, LSD, ketamine and exogenous cannabinoids, modulate astrocyte [Ca2+]i and thus synaptic currents in nearby neurons? (5) What is the role of ATP and adenosine in the above phenomena? (6) How do microglia regulate this signalling?
£162,047 25 Jun 2012