Hippocampal astrocytes encode reward location.

Astrocytic calcium dynamics has been implicated in the encoding of sensory information1-5, and modulation of calcium in astrocytes has been shown to affect behaviour6-10. However, longitudinal investigation of the real-time calcium activity of astrocytes in the hippocampus of awake mice is lacking. Here we used two-photon microscopy to chronically image CA1 astrocytes as mice ran in familiar or new virtual environments to obtain water rewards. We found that astrocytes exhibit persistent ramping activity towards the reward location in a familiar environment, but not in a new one. Shifting the reward location within a familiar environment also resulted in diminished ramping. After additional training, as the mice became familiar with the new context or new reward location, the ramping was re-established. Using linear decoders, we could predict the location of the mouse in a familiar environment from astrocyte activity alone. We could not do the same in a new environment, suggesting that the spatial modulation of astrocytic activity is experience dependent. Our results indicate that astrocytes can encode the expected reward location in spatial contexts, thereby extending their known computational abilities and their role in cognitive functions.

Features of hippocampal astrocytic domains and their spatial relation to excitatory and inhibitory neurons.

The mounting evidence for the involvement of astrocytes in neuronal circuits function and behavior stands in stark contrast to the lack of detailed anatomical description of these cells and the neurons in their domains. To fill this void, we imaged >30,000 astrocytes in hippocampi made transparent by CLARITY, and determined the elaborate structure, distribution, and neuronal content of astrocytic domains. First, we characterized the spatial distribution of >19,000 astrocytes across CA1 lamina, and analyzed the morphology of thousands of reconstructed domains. We then determined the excitatory somatic content of CA1 astrocytes, and measured the distance between inhibitory neuronal somata to the nearest astrocyte soma. We find that on average, there are almost 14 pyramidal neurons per domain in the CA1, increasing toward the pyramidal layer midline, compared to only five excitatory neurons per domain in the amygdala. Finally, we discovered that somatostatin neurons are found in close proximity to astrocytes, compared to parvalbumin and VIP inhibitory neurons. This work provides a comprehensive large-scale quantitative foundation for studying neuron-astrocyte interactions.