Abstract
Chemosensory systems exhibit substantial plasticity that supports adaptive perception, sensory learning, and behavioral responses to changing environmental and physiological conditions. Although synaptic mechanisms have traditionally been viewed as the principal basis of chemosensory plasticity, accumulating evidence indicates that adaptive sensory function depends on coordinated interactions among circuit modulation, glial regulation, metabolic and inflammatory state, and structural remodeling. This review synthesizes experimental findings showing how cortical feedback reshapes olfactory and broader chemosensory representations, how astrocytes and microglia regulate synaptic, metabolic, inflammatory, and remodeling environments, and how neurogenic and other structural mechanisms contribute to longer-term adaptation in experimental olfactory systems. On this basis, the review proposes an integrated multiscale framework in which cortical, glial, metabolic, inflammatory, genetic, and structural processes act as interconnected regulators of chemosensory plasticity rather than isolated contributors. Pharmacologically relevant entry points include neuromodulatory control of cortical feedback, astrocytic glutamate handling, purinergic signaling, metabolic support, microglial inflammatory responses, complement-associated synaptic remodeling, and neurotransmitter-dependent regulation of neurogenic niche dynamics. The framework also considers sirtuin 1 (SIRT1) as a candidate genetic and metabolic regulator linking cellular energy state, inflammation, oxidative stress, autophagy, synaptic plasticity, aging, and neurodegeneration, while emphasizing that its direct role in human chemosensory recovery remains unproven. Because smell and taste disturbances are prominent in aging, neurodegenerative disease, metabolic disorders, and post-viral conditions, this framework provides a basis for identifying context-dependent therapeutic strategies that may support sensory adaptation and recovery while avoiding disruption of beneficial inflammatory or remodeling responses.
Keywords
Chemosensory plasticity, Neuropharmacology, Olfactory dysfunction, Astrocytes, Microglia, Neuroinflammation, Pharmacological modulation, SIRT1