Regulation of auditory plasticity during critical periods and following hearing loss

Abstract

Sensory input has profound effects on neuronal organization and sensory maps in the brain. The mechanisms regulating plasticity of the auditory pathway have been revealed by examining the consequences of altered auditory input during both developmental critical periods-when plasticity facilitates the optimization of neural circuits in concert with the external environment-and in adulthood-when hearing loss is linked to the generation of tinnitus. In this review, we summarize research identifying the molecular, cellular, and circuit-level mechanisms regulating neuronal organization and tonotopic map plasticity during developmental critical periods and in adulthood. These mechanisms are shared in both the juvenile and adult brain and along the length of the auditory pathway, where they serve to regulate disinhibitory networks, synaptic structure and function, as well as structural barriers to plasticity. Regulation of plasticity also involves both neuromodulatory circuits, which link plasticity with learning and attention, as well as ascending and descending auditory circuits, which link the auditory cortex and lower structures. Further work identifying the interplay of molecular and cellular mechanisms associating hearing loss-induced plasticity with tinnitus will continue to advance our understanding of this disorder and lead to new approaches to its treatment.

Keywords: Aging; Auditory brainstem; Auditory cortex; Developmental critical periods; Hearing loss; Hidden hearing loss; Neuronal reorganization; Sensory deprivation; Synaptopathy; Tinnitus.

Fig. 1

Auditoryplasticity in development and adulthood inrodentmodels. A. Auditory development is characterized by multiple overlapping and successive critical periods (CPs) during which sensory representations are formed. CP timing is malleable and depends on the maturation of plasticity regulators. Following maturation, sensory representations are stable, and CPs can only be reopened if molecular brakes are lifted. A natural increase in dysregulated plasticity is observed with aging, which may be accelerated by hearing loss. B. Trajectory of tonotopic map development in the primary auditory cortex. Left: The juvenile tonotopic map is characterized by incomplete maturation prior to CP closure. Middle: Mature tonotopic representations form an orderly frequency gradient along the caudal to rostral axis. Right: Tonotopic disorganization has been observed with aging. C. Tonotopic map reorganization due to enhanced, CP-like, plasticity. Left: Passive tone pip exposure during the CP for tonotopic map plasticity results in an over-representation of the exposed tone frequency within the tonotopic map. Middle: Frequency over-representation can be induced in the adult cortex by pairing nucleus basalis stimulation with tone presentation. Right: Peripheral hearing loss in a restricted frequency range can result in an over-representation of the spared frequencies.

Fig. 2

Cellular, molecular, and circuit-levelmechanisms of cortical plasticity. Regulators of plasticity are shared by the juvenile and adult auditory cortex. Cortical development is marked by changes in inhibitory circuitry and the maturation of regulators that restrict plasticity. States of heightened plasticity similar to the immature brain can be reinstated by the removal of these plasticity regulators and experiences such as learning, acoustic over-exposure, or sensory deprivation. Abbreviations: A₁R: adenosine A1 receptor, BDNF: brain derived neurotrophic factor, GABA_AR: GABA_A receptor, lynx1: ly6/neurotoxin 1 protein, mAChR: muscarinic acetylcholine receptor, MGB: medial geniculate nucleus, nAChR: nicotinic acetylcholine receptor, NDNF: neuron-derived neurotrophic factor, PNN: perineuronal net, PV: parvalbumin, Pyr: pyramidal neuron, SST: somatostatin. VIP: vasoactive intestinal peptide.