| Summary: | Mouse IHCs, the main sensory cells of the mammalian cochlea, were studied using whole-cell patch clamp techniques. Recordings were made from 453 IHCs (ranging from EI4.5-P20) positioned at the two extremes of the cochlea. Changes in the properties of K+ currents, spiking activity, and Ca2+ currents along with synaptic vesicle exocytosis, were investigated. IRCs begin to express voltage-gated K+ currents from as early as EI4.5. During the next few days the appearance of the Ca2 + current allows IHCs to fire broad spontaneous action potentials. The growth of these currents from just after birth speeds up each action potential and increases the spike frequency with basal cells spiking more frequently than apical cells. The disappearance of spiking activity, that occurs just before the onset of hearing (P12), changes IHCs into mature sound transducers. It is likely that spiking activity is important for the reorganization of neuronal connections during early development as previously suggested in other systems (Moody, 1998). In order for spiking activity to function as a developmental signal to the afferent fibres, neurotransmitter must be released from IHCs. Capacitance measurements (indicative of synaptic vesicle exocytosis i.e. neurotransmitter release) indicated that IHCs responded to an action potential with exocytosis from late embryonic stages. Immature cells contain at least two kinetically distinct vesicle pools that seem to become depleted following stimuli greater than 1.5 s. By contrast, exocytosis in mature cells is more graded, with no apparent depletion for the same stimulus duration, and shows a higher Ca2+ -efficiency. These changes may enable IHCs to relay accurate auditory information onto afferent fibres. Overall, the results suggest that IHC maturation goes through different stages in order to fulfill their role in cochlear development incorporating changes in their basolateral currents and synaptic machinery. The aim of this thesis was to examine developmental changes in the properties of spiking activity among apical and basal IHCs and investigate any differences that exist between the two regions. The ability of IHCs to respond to an action potential with exocytosis was studied at different developmental stages and the maturation of vesicle release properties was compared between the two extremes of the cochlea.
|
|---|
