Astrocytic NFIX regulates thalamocortical circuits through GABA and purinergic signaling.
Astrocytes support synaptic activity and associated circuit function, including those linked to sleep and memory, though how they coordinate these processes remains poorly defined. Here, we show that the transcription factor Nuclear Factor I-X (NFIX) is required to maintain astrocyte function in the thalamic reticular nucleus (TRN), as its deletion results in aberrant thalamocortical oscillations and impaired memory formation. We found that NFIX directly regulates the expression of monoamine oxidase B (MAOB) and the purinergic receptor, P2RX7. Mechanistically, knockdown of Maob or knockout of P2rx7 in TRN astrocytes results in decreased astrocytic release of the neurotransmitter GABA, reducing tonic inhibition of ventrobasal (VB) relay neurons and impairing memory formation. Altogether, our studies identify region-specific roles for astrocytic NFIX and its gene regulatory network in TRN astrocytes, while further revealing that astrocytes in the TRN couple regulation of thalamocortical circuit dynamics and memory formation through parallel GABA and purinergic signaling pathways.