Sangroniz-Beltran, L. | Search bioRxiv

bioRxiv2026

Astrocytic morphology in the Medial Habenula: sex differences and modulatory factors

The medial habenula (MHb) is an epithalamic structure involved in aversive processing and emotional regulation, notable for its marked cellular heterogeneity and high astrocyte density. This cellular composition suggests that astrocytes may play an important role in MHb structure and plasticity, potentially contributing to the regulation of emotional states. The aim of this study is to characterize sex-dependent astrocytic morphology in the MHb and determine how it is modulated by peripheral alterations and direct central manipulations. A high-fat diet (HFD) was used as a model of metabolic stress, and systemic lipopolysaccharide (LPS) administration was used to induce a peripheral inflammatory challenge. At the central level, a chemogenetic approach using Gi-DREADDs under the GFAP promoter allowed selective modulation of astrocytic intracellular signalling independently of peripheral influences. Preliminary results indicate sex-dependent morphological differences in MHb astrocytes across all these experimental conditions, supporting the idea that MHb astrocytes are sensitive to both peripheral and central disturbances and may represent a key cellular substrate linking body-brain interactions with emotional regulation.

neuroscience↗

bioRxiv2025

NEUROGLIAL CB1 RECEPTORS CONTROL NAVIGATION STRATEGIES

Navigation and memory functions are essential for survival and are regulated by the hippocampus. These processes are tightly controlled, and one of the key modulators involved is the endocannabinoid system, particularly through the cannabinoid receptor type-1 (CB1). CB1 is widely expressed in various hippocampal cell types. While it is known that CB1 participates in memory processes, its specific roles in different cell types and how these roles may differ between sexes remain unclear. This study investigates how CB1 signaling in the hippocampus, in both, cell-type-specific and sex-dependent manner, contributes to navigation and memory. To this end, we selectively deleted CB1 receptors from neurons, CAMKII-expressing neurons, and astrocytes from the hippocampus of adult male and female mice. We then assessed its effect on a broad range of behaviors, including innate emotional responses, memory, navigation, and other hippocampus-related functions such as nesting. Deletion of CB1 in CAMKII-expressing neurons produced a pronounced effect in males, leading to increased anxiety and impairments in both reference and spatial memory. These mice also showed altered performance in the Barnes maze, relying less on spatial strategies. By contrast, females were less affected by this specific deletion. Interestingly, only deletion of CB1 from astrocytes led to spatial memory impairments in females, which also showed reduced LTP and a decreased reliance on spatial strategies in the Barnes maze. In conclusion, our findings show that neuronal CB1 receptors are critical for the spatial navigation strategy in males, while astrocytic CB1 receptors play a key role in memory processes both in males and females.

neuroscience↗