After substantial loss of cochlear hair cells, exogenous neurotrophins prevent degeneration of the auditory nerve. Because cochlear implantation, the current therapy for profound sensorineural hearing loss, depends on a functional nerve, application of neurotrophins is being investigated. We addressed two questions important for fundamental insight into the effects of exogenous neurotrophins on a degenerating neural system, and for translation to the clinic. First, does temporary treatment with brain-derived neurotrophic factor (BDNF) prevent nerve degeneration on the long term? Second, how does a BDNF-treated nerve respond to electrical stimulation? Deafened guinea pigs received a cochlear implant, and their cochleas were infused with BDNF for 4 weeks. Up to 8 weeks after treatment, their cochleas were analyzed histologically. Electrically evoked compound action potentials (eCAPs) were recorded using stimulation paradigms that are informative of neural survival. Spiral ganglion cell (SGC) degeneration was prevented during BDNF treatment, resulting in 1.9 times more SGCs than in deafened untreated cochleas. Importantly, SGC survival was almost complete 8 weeks after treatment cessation, when 2.6 times more SGCs were observed. In four eCAP characteristics (three involving alteration of the interphase gap of the biphasic current pulse and one involving pulse trains), we found large and statistically significant differences between normal-hearing and deaf controls. Importantly, for BDNF-treated animals, these eCAP characteristics were near normal, suggesting healthy responsiveness of BDNF-treated SGCs. In conclusion, clinically practicable short-term neurotrophin treatment is sufficient for long-term survival of SGCs, and it can restore or preserve SGC function well beyond the treatment period. SIGNIFICANCE STATEMENT Successful restoration of hearing in deaf subjects by means of a cochlear implant requires a healthy spiral ganglion cell population. Deafness-induced degeneration of these cells can be averted with neurotrophic factors. In the present study in deafened guinea pigs, we investigated the long-term effects of temporary (i.e., clinically practicable) treatment with brain-derived neurotrophic factor (BDNF). We show that, after treatment cessation, the neuroprotective effect remains for at least 8 weeks. Moreover, for the first time, it is shown that the electrical responsiveness of BDNF-treated spiral ganglion cells is preserved during this period as well. These findings demonstrate that treatment of the auditory nerve with neurotrophic factors may be relevant for cochlear implant users.

Because of its central position in the ascending auditory pathway, its large number of converging auditory brainstem inputs, and its fundamental role as a relay to auditory cortex and midbrain superior colliculus, the mammalian inferior colliculus (IC) is regarded pivotal for the integration of acoustic spectral–temporal cues to mediate sound-evoked behavior. However, detailed quantitative analyses of spectrotemporal neural responses are scarce. Moreover, most studies have been performed in anesthetized preparations, and it is unclear how to extrapolate findings to awake and behaving animals. Here, we characterize spectrotemporal receptive fields (STRFs) of single units in alert monkey IC by using a variety of broadband sounds with rippled amplitude spectra. We measured the response sensitivity to the ripple parameters density, Ω (cycles/octave), velocity,w(hertz), and direction selectivity,D. We observed a variety of dynamic STRFs, with a strong preference for low ripple densities, and a generally weak direction selectivity. Most cells preferred dynamic rippled stimuli above pure amplitude modulated noise (i.e., Ω = 0). Half of the cells could be characterized by good spectral–temporal separability, in which the ripple transfer function can be written asT(w, Ω) =F(w) ×G(Ω). Inseparability could be attributed to a difference in responses to up and downward direction with respect to both amplitude and temporal phase. We tested linearity of IC neurons by using the STRF to predict neural responses to natural stimuli and broadband noise and discuss our results in the light of findings obtained from auditory cortex.