Astrocytes in Reward and their Bidirectional Relationship with the Dopaminergic System

Astrocytes are currently investigated in a range of questions extending far beyond their traditional 'housekeeping' functions.

We have contributed to expanding the horizon of functions attributable to astrocytes, and have recently identified a novel and unexpected role for hippocampal astrocytes in signaling the location of reward.

This pioneering ERC project, will drive considerable progress in an important and completely unknown facet of reward-related information processing: the roles of hippocampal astrocytes in signaling reward, and their interaction with dopamine, the main player in the reward system. In Aim 1 we will define the role of hippocampal astrocytes in the perception of reward.

We will test whether astrocytes can encode the presences of reward irrespective of its location, based on non-spatial (auditory) cues.

By simultaneously imaging both astrocytes and neurons, we will delineate the spatio-temporal interplay between them in reward representation, and examine the projection-specific effect of astrocytes in rewarded behavior. Work on Aim 2 will delineate the effects of the dopaminergic system on astrocytes.

We will comprehensively analyse the distribution of dopamine receptors on astrocytes and the astrocytic response to tonic vs. phasic dopaminergic signals.

We will also perform simultaneous imaging of dopamine levels and astrocyte Ca2+ dynamics in different behavioral states. Aim 3 will determine how astrocytes mediate the effects of the dopaminergic system.

We will do that by manipulating astrocytic activity measure pre-synaptic dopamine axonal release in the hippocampus and its influence on the poorly understood phenomenon of over-representation of reward locations by neuronal place cells.Our published work and our new (unpublished) results generate the conceptual basis for this proposal and demonstrate its technical feasibility.

Achieving our goals will provide fundamental insights into the roles of astrocytes in information processing.