Neurotrophin 3 potentiates glutamatergic responses of IHC afferents in thecochlea in vivo

Neurotrophins have traditionally been regarded as slow-acting signals essen tial for neuronal survival and differentiation. Recent studies with neurona l slices, cultures and nerve ending preparations have shown that neurotroph ins generate acute changes in nerve activity. Among the secondary sensory c ells are the inner hair cells (IHC) and taste buds, cells which express the neurotrophic factors necessary for the survival of their innervating neuro ns. If in these cells neurotrophins acutely affect the nerve activity of th eir afferent neurons, as in the central nervous system (CNS), this may have important functional implications for the corresponding sensory transducti on processes. The neurotrophin NT-3 has been reported to be expressed in IH Cs. We chose an in vivo application system for the microiontophoretic suppl y of NT-3 in the subsynaptic region of the IHC. The effect of NT-3 on spont aneous and evoked afferent cochlear nerve activities in adult guinea pig in ner ear was studied. We observed that NT-3 rapidly increases the spontaneou s and glutamate-evoked firing rate of IHC afferents. Moreover, firing induc ed by both N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylis oxazole-4-propionic acid (AMPA) were specifically enhanced during the prese nce of NT-3, a process which was selectively blocked by the tyrosine kinase receptor inhibitor K252a. Because we localized NT-3 mRNA not only in IHCs but also in the spiral ganglion, we propose that similar to other sensory s ystems, afferent and autocrine neurotrophin activities may be responsible f or survival of cochlear neurons. In addition, NT-3 in IHCs may operate as a signal-dependent, intrinsic neuromodulator and/or neuroprotector.