Astrocytes are glial cells that participate in crucial processes in brain homeostasis and play a key role in modulating neuronal activity. Numerous astrocytic receptors transduce signals via cAMP although how changes in astrocytic cAMP levels modulate brain activity or animal behaviour is not fully understood. Our goal is to control cAMP in cortical astrocytes using DdPAC, a recently developed phytochrome photoreceptor that increases cAMP upon red light, and evaluate its responses at three levels: a) cellular, by analysing neuronal activity using multi-electrode arrays b) systemic, by measuring in vivo brain hemodynamics with a non-invasive custom-made diffusion wave imaging system c) behavioural, by analysing motor behaviour in a mouse model of Huntington’s disease. Activation of DdPAC by red light in cortical astrocytes induced synaptic potentiation in brain slices from WT mice, which was PKA/NMDA-dependent and Ca2+-independent. Then, we observed that DdPAC stimulation induced an increase in blood flow in both WT and HD anesthetized mice. We finally assessed motor behaviour both in WT and HD mice after repetitive DdPAC stimulation and observed distinct effects between genotypes: while motor learning was improved in WT mice, coordination was impaired in HD mice. Altogether, our data demonstrates that light-dependent modulation of cAMP in astrocytes with phytochromes could improve synaptic plasticity in neurons and increase brain activity in specific brain areas. Furthermore, in vivo manipulation of cAMP in astrocytes generated divergent responses in WT and HD mice, which is relevant to further exploring therapeutic opportunities to ameliorate symptoms in neurodegenerative diseases.