ASTROCYTE MORPHOLOGICAL AND SYNAPTIC PLASTICITY IN THE ANTERIOR CINGULATE CORTEX AND ITS ROLE IN THE REGULATION OF VOLUNTARY BEHAVIOR

Astrocytes are glial cells that play fundamental roles in regulating brain structure and function since they are key modulators of synaptic plasticity and synaptogenesis. They exhibit a complex morphology that is altered in many neurological and neuropsychiatric disorders. The juxtaposition of their Perisynaptic Astrocytic Processes to pre- and post-synaptic structures forms what is known as tripartite synapse, where the astrocyte modulatory activity takes place. Astrocytes respond to synaptic activity through extension and retraction of their numerous processes, but it remains unclear whether astrocytic structural plasticity affects voluntary behaviors in physiological conditions. The aim of this study is to investigate the role of astrocyte structural plasticity and its molecular regulators in brain circuits controlling voluntary goal-directed behaviors and their relationship with structural synaptic plasticity. We compared astrocytic process plasticity and excitatory and inhibitory synapses in trained versus untrained mice during operant training. Mice were trained under an increasing fixed-ratio (FR) schedule, learning to press a lever 1, 5, and 10 times to obtain a single food reinforcer. Whole-astrocyte imaging was performed in the anterior cingulate cortex, a region involved in effort–reward balance. Expansion microscopy was applied to improve the resolution of the smallest astrocytic processes. To identify molecular regulators of astrocyte structural changes associated with effort exertion, we performed astrocyte-specific TRAP-seq in untrained and FR10-trained mice. This study provides initial evidence for a role of astrocyte structural plasticity in modulating neuronal circuits controlling voluntary behaviors and identifies novel molecular markers associated with these changes.