Astrocyte-neuron interactions in vivo during cortical plasticity and learning

Our laboratory has revealed novel and critical roles for astrocytes in brain function. By two-photon imaging of neurons and astrocytes in the visual cortex in vivo, we showed that astrocyte calcium responses sensitively reflect neuronal activity. Astrocyte signals are importantly mediated via glutamate transporters on processes that surround synapses, and they influence local blood flow and hence the hemodynamic signals that underlie brain imaging methods such as functional magnetic resonance imaging (fMRI). Astrocytes are also activated by neuromodulators such as acetylcholine and norepinephrine, and we discovered that cholinergic inputs in the adult brain can act via astrocytes to alter the strength of excitatory synapses and implement plasticity of neuronal responses. Furthermore, astrocyte calcium signaling influences excitatory drive to inhibitory neurons, thereby enabling astrocytes to modulate excitatory-inhibitory balance in neuronal circuits.

Recently, we have measured fluorescently-labeled dendritic spines and Ca2+ signaling in astrocytes processes in vivo. One way for astrocytes to influence synaptic transmission at dendritic spines is by clearing glutamate from the synaptic cleft. Astrocytes regulate glutamate at the synapse with glutamate transporters (GluTs), of which they express two major types: Glt-1 and GLAST. Of the two, Glt-1 is more abundant in the cortex. We investigate the relationships between astrocytes and neurons by:
• monitoring the structural/functional relationship between dendritic spines and astrocytes processes in the visual cortex using 2-photon calcium and/or glutamate imaging in behaving mice in response to visual stimuli;
• examining structural/functional alterations resulting from developmental plasticity in the visual cortex;
• investigating astrocyte-neuron interactions during visual learning in awake behaving mice.

Taken together, these approaches examine the functional interactions between neurons and astrocytes at a scale and time course not currently represented in the literature, and promise to sharpen our understanding of how astrocytes respond to and subsequently modify neuronal responses.