ELECTROPHYSIOLOGICAL CHARACTERIZATION OF NEURONAL ACTIVITY IN CORTICO-LIMBIC CIRCUITS LACKING ASTROCYTIC EXOCYTOSIS

Recent studies have fundamentally reshaped our understanding of astrocytes, establishing them as active regulators of synaptic transmission, network coordination, and cognition rather than passive support cells. Astrocytes are now recognized as integral components of the tripartite synapse, engaging in bidirectional communication with neurons by detecting, integrating, and modulating synaptic signals. A central mechanism underlying astrocyte–neuron communication is astrocytic exocytosis, through which astrocytes release signals that influence synaptic and circuit-level activity. Evidence from genetic disruption models, particularly the dominant-negative SNARE (dnSNARE) mouse, demonstrates that impairing astrocytic exocytosis alters cortico-limbic network dynamics and cognitive performance. Notably, Sardinha et al. (2017) showed that astrocyte-dependent signaling is essential for hippocampal–prefrontal theta synchronization and executive function, identifying astrocytic exocytosis as a key modulator of long-range circuit coordination. Despite these advances, the circuit-level mechanisms by which astrocytic exocytosis shapes neural dynamics remain poorly understood, largely due to the lack of tools enabling precise spatial and temporal control of astrocytic release. To address this gap, the present study combines established and novel astrocyte-specific approaches to investigate the contribution of astrocytic exocytosis to hippocampal network function. We will use the dnSNARE model as a benchmark for brain-wide disruption of astrocytic exocytosis and an innovative miniSOG-based tool to achieve local, temporally restricted suppression of astrocytic exocytosis in the dorsal hippocampus. Using high-density electrophysiological recordings in the dorsal hippocampus and medial prefrontal cortex, we characterized network and single-unit signatures associated with astrocytic exocytosis, providing mechanistic insight into hippocampal–prefrontal communication and cognitive network organization.