Loss of function mutations in the X-linked gene encoding for MeCP2 are the underlying genetic cause for Rett Syndrome (RTT), a devastating neurodevelopmental disorder that primarily affects girls. While the function of this transcriptional regulator remains elusive and complex, recent focus has turned to downstream signaling pathways as putative targets for novel therapeutics. The complexity of MeCP2 function is compounded by the heterogeneity of cell types in the brain, with recent evidence implicating glia cells in RTT pathophysiology. The focus of my thesis has been two-fold: exploring signaling mechanisms downstream of MeCP2 and the potential of IGF-1 as a therapeutic for RTT, and examining functional astrocyte sensory processing in healthy and impaired circuits. We show that IGF-1 levels are reduced in mouse models of RTT and systemic treatment with IGF-1 leads to improvements in lifespan, respiratory patterns, and social behaviors. These effects are accompanied by increased synaptic proteins, activation of signaling pathways, and enhanced excitatory transmission, as well as effects on plasticity in visual cortex circuits. Astrocytes, known to contribute to synapse formation and maintenance, have been implicated alongside neurons as contributors to the RTT phenotype. They express the two most abundant glutamate transporters in the brain responsible for the majority of glutamate clearance from synapses. Indeed, lack of MeCP2 in astrocytes leads to aberrant glutamate clearance, with strong implications for neuronal activity. Efficient processing of visual information requires processing salient features while overcoming the inherent variability in neuronal networks. Natural movies evoke reliable responses from pyramidal neurons in visual cortex and my work reveals that discrete microdomain regions of visual cortex astrocytes also exhibit reliable responses to natural scenes. We tested the hypothesis that glutamate transporters, which influence astrocytic Ca2+ signaling and synaptic transmission, may be a functional component to processing of visual information. Finally, we investigated sensory processing features of astrocytes in a RTT mouse model in which we have found aberrant glutamate transporter expression.