In a paper published in Cell, researchers at The Hebrew University of Jerusalem showed that activating astrocytes in the hippocampus, rather than direct neuronal activation, could improve memory.
Previous studies have shown that astrocytes modulate synaptic activity and are required for neuronal plasticity and memory performance. However, whether astrocytes play a supportive role or actively promote neuronal network development is unknown.
To probe how astrocyte activity affects neuronal plasticity and memory in mice, the scientists engineered astrocytes in the memory-associated region of the brain to express an engineered receptor that increases astrocyte activity in response to clozapine-N-oxide (CNO).
In hippocampus slices from the mice, CNO increased postsynaptic neuronal activity compared with vehicle, showing that stimulating astrocyte activity improves neuronal synaptic responses.
Behavioral tests in the mice showed that CNO increased exploratory behavior and learned contextual fear responses, suggesting that astrocyte activation increased spatial and contextual memory. In an optogenetic mouse model, photostimulation of astrocytes led to similar behavioral results.
However, directly activating neurons in the hippocampus in mice had no effect on exploratory behaviors and decreased learned fear responses compared with vehicle, showing neuronal activation impairs memory performance.
In the paper, the authors suggested reassessing the activity of astrocytes in neural network development and investigating whether astrocyte modulation could be translated into cognitive augmentation therapies.