Astrocytes provide the temporal dynamic required for memory formation

Theta oscillations (4-12 Hz) in the hippocampus, driven by synchronous neuronal bursts, are essential for grouping and selecting neuronal ensembles during spatial navigation, memory, and learning 1,2. Yet, the specific mechanisms enabling this frequency band to effectively modulate neuronal ensembles remain unclear. Here, we show that burst activity at the CA3-CA1 synapse in the mouse hippocampus initiates rapid activation of astrocytic leaflets. This activation is mediated by retrograde messengers, which in turn activate transient receptor potential channels in astrocytes, potentiating glutamate release from Schaffer collaterals via the activation of presynaptic glutamate receptors. We show that this mechanism is synapse-specific and necessary for the induction of long-term potentiation (LTP). Remarkably, this positive feedback loop peaks 50 to 200 ms after a burst, precisely aligning with the theta frequency range and optimizing reinforcement of neuronal activity. These findings indicate that astrocytes provide critical timing to potentiate synaptic transmission during the initial phases of learning and memory formation.