Noradrenergic modulation of contextual memory encoding through hippocampal astrocyte α1A receptors.

A key property of the brain is its capacity to form and store memories, enabling it to act on experience to guide future behaviour. One of the major findings in neuroscience over the past decade was the revelation that astrocytes not only provide metabolic and structural support for neurons, but can directly modulate neuronal activity to promote memory formation. The dentate gyrus of the
hippocampal formation is critical for the specificity of contextual memories. It organizes incoming contextual information into highly individual cellular representations in a process termed pattern separation. I propose that astrocytes respond to altered arousal levels, such as increased vigilance or during salient stimuli, to fine-tune local synaptic activity in the dentate gyrus. Indeed, astrocytes can sense elevations of noradrenaline through activation of α1A adrenoreceptors, and using selective knockout of these receptors in astrocytes, I have demonstrated that this process can regulate synaptic input into the dentate gyrus. I will use a challenging combination of tools including electrophysiology, neuronal activity tagging, calcium fibre photometry and optogenetic stimulation to uncover how astrocyte α1A adrenoreceptors regulate dentate gyrus pattern separation and contextual memory discrimination. I propose that astrocytes may be an essential non-neuronal engram component that responds to arousal levels to ensure the discrimination between similar experiences.