Photoactivated adenylyl cyclase in cortical astrocytes promotes synaptic potentiation and reveals alterations in Huntington's disease.

ABSTRACT: Coordinated neuron-astrocyte interactions are crucial for synaptic plasticity and brain function. Cyclic adenosine monophosphate (cAMP) pathways have a key role in modulating plasticity and are disrupted in neurodegenerative diseases. Yet, the role of astrocytic cAMP remains unclear. We addressed this by expressing the photoactivatable adenylyl cyclase DdPAC in cortical astrocytes, enabling cAMP synthesis under red light stimulation. Using electrophysiological and comprehensive proteomic analyses, we determined its effects in wild-type mice. The modulation of astrocytic cAMP triggered long-term synaptic potentiation and rapidly induced the phosphorylation of proteins involved in synaptic transmission, including PKA. In Huntington's Disease (HD) models, DdPAC activation in cortical astrocyt

SUBMITTER: Sitja-Roqueta L 

PROVIDER: S-EPMC12554215 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature