Astrocyte control of neural circuits and behavior


September 20, 2016 - 12:00pm - 1:00pm
About the Speaker
Marc Freeman
Speaker Affiliation: 

Whether astrocytes play direct roles in information processing in the brain remain unclear and controversial. Astrocytes associate with synapses throughout the brain and express receptors for neurotransmitters that can elevate intracellular Ca2+. Astrocyte Ca2+ signaling has been proposed to modulate neural circuit activity, but molecular pathways regulating these events are poorly defined and in vivo evidence linking changes in astrocyte Ca2+ to alterations in neurotransmission or behavior is limited. We have found that Drosophila astrocytes exhibit robust activity-regulated Ca2+ signaling events in vivo. Tyramine (Tyr) and octopamine (Oct) (the invertebrate equivalents of epinephrine and norepinephrine) released from Tdc2+ neurons signal directly to astrocytes to stimulate Ca2+ increases through a GPCR receptor and TRP channel, and astrocytes in turn modulate downstream dopaminergic (DA) neuron activity. Tyr or Oct application to live preparations silenced DA neurons and this inhibition required the astrocytic GPCR signaling cascade. Increasing astrocyte Ca2+ signaling was sufficient to silence DA neuron activity, which was mediated by astrocyte endocytic function and adenosine
receptors. Selective disruption of astrocyte GPCR/TRP channel signaling blocked astrocyte Ca2+ signaling and profoundly altered olfactory-driven chemotaxis behavior and touch-induced startle responses. This work identifies key components of the astrocyte Ca2+ signaling machinery, provides direct evidence that neuromodulation can be mediated directly by astrocytes, and demonstrates that astrocytes are essential for multiple sensory-driven behaviors.