Abstract
New neurons are continuously generated from stem cells and integrated into the adult hippocampal circuitry, contributing to memory function. Several environmental, cellular, and molecular factors regulate the formation of new neurons, but the mechanisms that govern their incorporation into memory circuits are less explored. Herein we will focus on microglia, the resident immune cells of the CNS, which modulate the production of new neurons in the adult hippocampus and are also well suited to participate in their circuit integration. Microglia may contribute to the refinement of brain circuits during development and exert a role in physiological and pathological conditions by regulating axonal and dendritic growth; promoting the formation, elimination, and relocation of synapses; modulating excitatory synaptic maturation; and participating in functional synaptic plasticity. Importantly, microglia are able to sense subtle changes in their environment and may use this information to differently modulate hippocampal wiring, ultimately impacting on memory function. Deciphering the role of microglia in hippocampal circuitry constant rewiring will help to better understand the influence of microglia on memory function.
Highlights
The generation of hippocampal neurons during adulthood has been implicated in critical brain functions, such as memory formation, and pathological conditions, including mood disorders
The hippocampal connectivity is characterized by the wellknown tri-synaptic circuit, in which pyramidal cells located in layer II of the entorhinal cortex (EC) connect to dentate gyrus (DG) granule cells (GCs), which send their output signal to the Cornu Ammonis subfield 3 (CA3)
The involvement of maturing GCs in memory function indicates that memory may be affected by those factors that regulate the integration of these cells into the hippocampus, such as neuronal activity, which is initially sensed by neuroblasts in the form of tonic GABA and later in the form of inputs from inhibitory and excitatory local circuits (Ge et al, 2006; Jagasia et al, 2009; Song et al, 2013; Alvarez et al, 2016)
Summary
The generation of hippocampal neurons during adulthood has been implicated in critical brain functions, such as memory formation, and pathological conditions, including mood disorders. We will focus on the contribution of microglia, the resident immune cells of the CNS, to the incorporation of adult generated neurons into hippocampal memory circuits. Microglia are especially well equipped to sense changes in the brain parenchyma and to interact with other cell types such as neurons and astrocytes (Kettenmann et al, 2011), and they are good candidates to act as mediators of the adaptive incorporation of newly generated neurons into hippocampal circuits, few studies have addressed the role of microglia on neurogenesis directly (Valero et al, 2016, 2017). We will briefly introduce microglia and summarize their main functions in different contexts, such as development, adulthood or pathology, which may be relevant for the integration of new generated neurons into memory circuits. We will discuss evidence that suggest that microglia effectively play a role in neurite growth as well as in the structural and functional maturation of newborn neurons
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