Brain development and learning is accompanied by morphological and molecular changes in neurons. The growth associated protein 43 (Gap43), indicator of neurite elongation and synapse formation, is highly expressed during early stages of development. Upon maturation of the brain, Gap43 is down-regulated by most neurons with the exception of subdivisions such as the CA3 region of hippocampus, the lateral superior olive (LSO) and the central inferior colliculus (CIC). Little is known about the regulation of this mRNA in adult brains. We found that the expression of Gap43 mRNA in specific neurons can be modulated by changing sensory activity of the adult brain. Using the central auditory system of rats as a model, Gap43 protein and mRNA levels were determined in LSO and CIC of hearing-experienced rats unilaterally or bilaterally deafened or unilaterally stimulated by a cochlear implant (CI). Our data indicate that Gap43 is a marker useful beyond monitoring neuronal growth and synaptogenesis, reflecting also specific patterns of synaptic activities on specific neurons. Thus, unilateral loss of input to an adult auditory system directly causes asymmetrical expression of Gap43 mRNA between LSOs or CICs on both sides of the brainstem. This consequence can be prevented by simple-patterned stimulation of a dysfunctional ear by way of a CI. We suggest that as a function of input balance and activity pattern, Gap43 mRNA expression changes as cells associate converging afferent signals.

Currently, there is controversy around whether rats can use interaural time differences (ITDs) to localize sound. Here, naturalistic pulse train stimuli were used to evaluate the rat's sensitivity to onset and ongoing ITDs using a two-alternative forced choice sound lateralization task. Pulse rates between 50 Hz and 4.8 kHz with rectangular or Hanning windows were delivered with ITDs between ±175 μs over a near-field acoustic setup. Similar to other mammals, rats performed with 75% accuracy at ∼50 μs ITD, demonstrating that rats are highly sensitive to envelope ITDs.

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Cochlear implants (CIs) can restore a high degree of functional hearing in deaf patients but enable only poor spatial hearing or hearing in noise. Early deaf CI users are essentially completely insensitive to interaural time differences (ITDs). A dearth of binaural experience during an early critical period is often blamed for these shortcomings. However, here we show that neonatally deafened rats which are fitted with binaural CIs in early adulthood are highly sensitive to ITDs immediately after implantation. Under binaural synchronized stimulation they can be trained to localize ITDs with essentially normal behavioral thresholds near 50 μs. This suggests that the deficits seen in human patients are unlikely to be caused by lack of experience during their period of deafness. It may instead be due to months or years of CI stimulation with inappropriate binaural parameters provided by CI processors which do not provide sub-millisecond temporal fine structure of sounds . 3 33 34 35 36 37 38 39 40 41 42 43 44 45 The World Health Organization reports that about 466 million people suffer from disabling hearing loss, making it the most common sensory impairment of our age. For people with severe to profound sensorineural hearing loss, cochlear implants (CIs) can be enormously beneficial, quite routinely allowing near normal spoken language acquisition, particularly when CI implantation takes place early in life [1]. Never the less the performance of CI users remains variable, and even in the best cases falls short of natural hearing.Good speech understanding in multi-sound environment requires the ability to separate speech from background, which relies in part on a phenomenon known as "spatial release from masking". This relies on the brain's ability to process binaural spatial cues, including interaural level and interaural time differences (ILDs/ITDs) [2]. To benefit from binaural cues in everyday life, bilateral cochlear implantation is becoming increasingly common for deaf patients [3][4][5] . However, even binaural CI patients perform much below the level of normal listeners in sound localization or auditory scene analysis tasks, particularly when multiple sound sources are present [6,7]. The parameters that would allow CI patients to derive maximum benefits from binaural spatial cues are still only partially understood. A number of technical problems (see [8], chapter 6) limit the fidelity with which CIs can encode binaural cues, particularly ITDs. The fact that contemporary CI speech processors were originally designed for monaural, rather than binaural, hearing likely contributes the observed deficits in ITD performance of bilateral CI users [3]. Standard CI processors provide pulsatile stimulation which is not locked to the temporal fine structure of the incoming sounds, and the timing of the electrical pulses is not synchronized between both ears, which makes these devices fundamentally incapable of encoding sub-millisecond binaural time structure. To be useful, ITDs as small as a few tens ...