Abstract
Synaptic plasticity is a critical mechanism underlying the long‐term retention of information in the brain. In particular, dendritic spines-postsynaptic structure of excitatory synapses located in the neocortex, hippocampus, and striatum-play a pivotal role in synaptic plasticity, named structural long‐term potentiation (sLTP) . sLTP has been extensively studied in the hippocampus and striatum. In contrast, its mechanisms in the neocortex remain poorly understood, although the neocortex is a central brain region involved in processing of sensory, motor and emotional information. Notably, synaptic plasticity declines with maturation in the neocortex according to ex vivo studies, but spine plasticity persists into adulthood based on in vivo observations, presenting an unresolved enigma. Our recent findings reveal that sLTP is prominent during juvenile but becomes suppressed in adulthood through regulation by microglia via TNF‐α. However, this inhibition can be reversed in adulthood by noradrenaline (NA) , which acts through microglial β2‐adrenergic receptors to promote sLTP. Moreover, this signaling contributes to the establishment of observational fear learning (OFL) . These results highlight an emergence of developmental balance of microglia and noradrenaline to modulate neocortical synaptic plasticity and learning in the neocortex.
