Instructive roles of astrocytes in hippocampal synaptic plasticity: neuronal activity-dependent regulatory mechanisms

In the adult hippocampus, synaptic plasticity is important for information processing, learning, and memory encoding. Astrocytes, the most common glial cells, play a pivotal role in the regulation of hippocampal synaptic plasticity. While astrocytes were initially described as a homogenous cell population, emerging evidence indicates that in the adult hippocampus, astrocytes are highly heterogeneous and can differentially respond to changes in neuronal activity in a subregion-dependent manner to actively modulate synaptic plasticity. In this review, we summarize how local neuronal activity changes regulate the interactions between astrocytes and synapses, either by modulating the secretion of gliotransmitters and synaptogenic proteins or via contact-mediated signaling pathways. In turn, these specific responses induced in astrocytes mediate the interactions between astrocytes and neurons, thus shaping synaptic communication in the adult hippocampus. Importantly, the activation of astrocytic signaling is required for memory performance including memory acquisition and recall. Meanwhile, the dysregulation of this signaling can cause hippocampal circuit dysfunction in pathological conditions, resulting in cognitive impairment and neurodegeneration. Indeed, reactive astrocytes, which have dysregulated signaling associated with memory, are induced in the brains of patients with Alzheimer's disease (AD) and transgenic mouse model of AD. Emerging technologies that can precisely manipulate and monitor astrocytic signaling in vivo enable the examination of the specific actions of astrocytes in response to neuronal activity changes as well as how they modulate synaptic connections and circuit activity. Such findings will clarify the roles of astrocytes in hippocampal synaptic plasticity and memory in health and disease.