Beyond their multiple homeostatic activities, astrocytes have an essential role in information processing in the brain. Interestingly, Doron et al. (Nature, 2022) showed that hippocampal astrocytes exhibit persistent ramping activity as mice approach a reward in a familiar virtual reality environment, but not in a novel one. This suggests that astrocytes can encode expected reward locations; however, it remains unclear whether they encode the reward itself or the environment. Thus, astrocytic reward encoding outside spatial contexts remains unexplored. Additionally, astrocytic dysfunction is considered a key contributor to Major Depressive Disorder (MDD), a condition characterized by impaired reward encoding. I aim to test the hypothesis that the effect of astrocytes on MDD is mediated by a disruption of their reward encoding. To investigate this, I conduct real-time calcium imaging of hippocampal CA1 astrocytes in mice navigating a custom-designed auditory environment, that represents non-spatial distance to a reward. Initial results indicate that the number of concurrent astrocytic calcium events increases towards the reward in the familiar auditory environments. This ramping does not persist in novel auditory environments but reestablishes after training. In my future research, I plan to image both astrocytes and neurons in this paradigm, to unravel the temporal and spatial interplay between them in reward signaling. Ultimately, I will use the Chronic Mild Stress model of depression and will perform dual imaging in mice exhibiting depressive-like symptoms. This will allow me to test the hypothesis that impairment in reward encoding by astrocytes contributes to MDD, via their communication with neurons.

Supervisor: Prof. Inbal Goshen