Olena Bukalo

Talk: "Functional Roles of Astrocyte Calcium Elevations in the Basolateral Amygdala"

The ability to retrieve associations between environmental stimuli and previously encountered threat represents a fundamental form of memory crucial to survival. Recent studies suggest astrocytes support fear memory by modulating memory-encoding neural circuits and neuronal engrams in cortical and limbic regions. However, the precise mechanisms by which this occurs remain unknown. We monitored and manipulated astrocyte activity in vivo with fiber photometry in the basolateral amygdala (BLA), a brain region critical to the formation, retrieval, and extinction of fear memories. First, our data demonstrate that population BLA astrocyte Ca2+ activity signals the retrieval of a cued threat memory then tracks the extinction-induced shift from a high to low fear state and subsequent return of high fear during context-driven renewal. Next, we found that genetic manipulations aimed to reduce Ca2+ activity in astrocytes impair formation/retrieval of fear memory. To further dissociate the significance of astrocytic Ca2+ signaling in fear memory, we employed a chemogenetic manipulation by expressing viral constructs for hM3D(Gq)- or hM4D(Gi)--coupled DREADD in BLA astrocytes. Systemic injection of the inert ligand clozapine n-oxide (CNO), prior to extinction training, have an opposite effect on freezing behavior. We found that freezing levels were markedly lower in hM3D-, but higher in hM4D-expressing animals as compared to mice expressing control viral construct, during early extinction trials, consistent with an impairment or improvement in fear memory retrieval. Using in vivo fiber photometry Ca2+ imaging during CNO application, we observed a different dynamic of Ca2+ signal in astrocytes in hM3D- and hM4D-expressing animals. Altogether, our data suggests that Ca2+ responses in astrocytes are not only tightly correlated with fear state, but also that BLA astrocyte Ca2+ activity is necessary for fear memory retrieval. Future studies will investigate how astrocytes are implicated in shaping neuronal networks in the amygdala during fear memory acquisition and retrieval.

Research supported by the NIAAA Intramural Research Program.