Priming central sound processing circuits through induction of spontaneous activity in the cochlea before hearing onset

• Published in: Trends in neurosciences (Regular ed.) 2024-07, Vol.47 (7), p.522-537
• Main Authors: Kersbergen, Calvin J., Bergles, Dwight E.
• Format: Article
• Language: English
• Subjects: Animals; astrocyte; auditory cortex; auditory development; Auditory Pathways - physiology; Auditory Perception - physiology; cochlea; Cochlea - physiology; connexin 26; Hair Cells, Auditory - physiology; Hearing - physiology; Humans; supporting cells
• ISSN: 0166-2236; 1878-108X; 1878-108X
• DOI: 10.1016/j.tins.2024.04.007

Spontaneous bursts of neural activity in the developing auditory system prior to hearing onset are generated by inner supporting cells (ISCs), which depolarize adjacent inner hair cells (IHCs) by locally increasing extracellular potassium.Restricted spatiotemporal IHC activation in the cochlea induces correlated firing of neurons aligned to isofrequency lamina within central auditory centers.Astrocyte calcium transients are induced by engagement of metabotropic glutamate receptors following glutamate spillover from active synapses during neuronal burst firing.Disruption of spontaneous activity in the cochlea leads to increased gain, impaired synaptic refinement, and altered tonotopic maps in auditory centers of the CNS.Spontaneous activity is preserved in many models of congenital deafness, which may enable initial circuit maturation, increasing the efficacy of later restorative interventions. Sensory systems experience a period of intrinsically generated neural activity before maturation is complete and sensory transduction occurs. Here we review evidence describing the mechanisms and functions of this ‘spontaneous’ activity in the auditory system. Both ex vivo and in vivo studies indicate that this correlated activity is initiated by non-sensory supporting cells within the developing cochlea, which induce depolarization and burst firing of groups of nearby hair cells in the sensory epithelium, activity that is conveyed to auditory neurons that will later process similar sound features. This stereotyped neural burst firing promotes cellular maturation, synaptic refinement, acoustic sensitivity, and establishment of sound-responsive domains in the brain. While sensitive to perturbation, the developing auditory system exhibits remarkable homeostatic mechanisms to preserve periodic burst firing in deaf mice. Preservation of this early spontaneous activity in the context of deafness may enhance the efficacy of later interventions to restore hearing. Sensory systems experience a period of intrinsically generated neural activity before maturation is complete and sensory transduction occurs. Here we review evidence describing the mechanisms and functions of this ‘spontaneous’ activity in the auditory system. Both ex vivo and in vivo studies indicate that this correlated activity is initiated by non-sensory supporting cells within the developing cochlea, which induce depolarization and burst firing of groups of nearby hair cells in the sensory epithelium, activit