Functional development and differentiation of mammalian vestibular hair cells and their synapses.

In the vestibular inner ear, multiple hair-cell organs decompose head movements into angular or linear components with distinct planes of action, time course, frequencies, and amplitudes. The hair cell responses are transmitted to vestibular afferents and propagated to the brain, where the signals contribute to orientation and heading perception and drive reflexes that stabilize vision and posture during movement. Mammalian and other amniote vestibular epithelia feature two hair cell types (I and II) with distinctive afferent synaptic contacts (calyx and bouton) and transmission mechanisms (nonquantal versus quantal), and are organized into central and peripheral zones that generate afferent populations with fundamentally different encoding properties. In altricial rodents like mice, physiological differences between hair cells, afferents and zones emerge prenatally and develop over several postnatal weeks. The mouse utricle is a model system for investigating developmental differentiation of afferent signals by virtue of its highly organized epithelium, accessibility of immature stages, and genetic tractability. Physiological studies demonstrate that selective acquisition of low-voltage-activated potassium channels from the K_V1 (Kcna) and K_V7 (Kcnq) families profoundly shapes the maturing sensory signal at multiple stages: hair cell receptor potentials become faster, synaptic transmission from type I hair cells becomes nonquantal, and afferent spike patterns become more irregular. Targeted genetic manipulations coupled with behavioral assessments have revealed transcription factors that regulate the physiological differentiation of hair cell and afferent types. Developmental mechanisms to create new hair cells, hair bundles and functional synapses persist at low levels in mature vestibular epithelia, allowing some regeneration and repair to sustain transduction and transmission for years.