RX8 Multi-I/O Processor

Aging and noise over-exposure lead to complex mixtures of cochlear degradation that impair the structure and function of outer hair cells (OHCs), inner hair cells (IHCs), and the cochlear nerve. However, IHC damage and cochlear synaptopathy (CS) remain pathologies "hidden" from the audiogram. This study aimed to compare and contrast the physiological signatures of these two popular and distinct exposure paradigms using promising non-invasive assays: Envelope Following Responses (EFRs), Auditory Brainstem Response (ABRs), Wideband Middle-Ear Muscle Reflexes (WB-MEMRs), and Distortion Product Otoacoustic Emissions (DPOAEs). We utilized chinchilla models of carboplatin exposure (CA) (N = 4) and temporary threshold shift (TTS) noise-induced CS (N = 4) to compare the physiological signatures of each type of exposure. While both groups showed unchanged ABR thresholds two weeks after exposure, EFRs, ABR Wave 5/1 ratios, and MEMRs showed distinct effects of exposure. CA and TTS exposures showed differences in the pattern and degree of decreased EFR "peakiness" across different stimulus modulation types (e.g., sinusoidal vs. rectangular). Significant elevations in ABR Wave 5/1 ratios were less-pronounced in the TTS-exposed animals. Reduced WB-MEMR amplitudes and increased WB-MEMR thresholds occurred in both groups, although this effect was more pronounced for TTS. Opposite trends in DPOAE amplitudes suggest that effects on OHC integrity and auditory efferent physiology may differ between the two exposure types and their induced pathologies. Overall, these results suggest a combination of EFR "peakiness", ABR Wave 5/1 ratio, and WB-MEMR may be useful for profiling IHC dysfunction and CS as potentially distinct forms of hidden hearing loss.

Instrumental learning typically requires hundreds to thousands of trials in which subjects learn to link motor responses to sensory cues. In standard rodent protocols, response accuracy is reported only at trial end, preventing subjects from correcting erroneously initiated responses. We hypothesized that within-trial, closed-loop sensory feedback would accelerate instrumental learning by providing real-time information about response correctness. Head-fixed mice performed a two-alternative forced-choice task by rotating a choice wheel in response to sensory cues. Mice received either no feedback (n = 18), auditory feedback (n = 16), or audiovisual feedback (n = 4) coupled to wheel movements. Feedback-receiving mice required significantly fewer trials to reach 70 % accuracy criterion (median: 3186, 4918 and 7329 trials for multimodal, unimodal and no feedback, respectively; p = 0.0245) and showed higher accuracy when modifying choices (expert stage: 17 %, 11 % and 9 % accuracy in trials with modified choices for multimodal, unimodal and no feedback, respectively; p=1.04×10⁻⁶). Only feedback mice displayed movement refinements across training (p = 8.02×10⁻⁶, p = 4.07×10⁻¹⁸ and p = 0.2602 for multimodal, unimodal and no feedback, respectively). In summary, closed-loop sensory feedback accelerated instrumental acquisition, demonstrating its value as routine training protocol. HIGHLIGHTS Mice provided with feedback require fewer trials to reach expert stage in an instrumental learning task Mice provided with feedback perform with higher accuracy in trials involving ‘changes of mind’ Movement trajectories of mice provided with feedback undergo refinement as training advances Sensory feedback can be used as a training aid to accelerate instrumental learning

Nervous systems generate predictions using internal copies of motor commands, termed corollary discharge (CD). CD modulates sensory neurons to distinguish self-generated sensory inputs (reafference) from external inputs (exafference). As behavior changes throughout development and evolution, these predictions must update as reafference changes. However, mechanisms that synchronize CD to reafferent input remain unknown. Mormyrid fish communicate using electric organ discharges (EODs). To distinguish reafferent and exafferent EODs, a CD inhibits sensory neurons whenever a reafferent EOD is produced. EOD duration varies across and within species, and a yet-unknown mechanism precisely time-locks inhibition with reafference. Likewise, seasonal increases in testosterone reversibly elongate male EODs in some species, and testosterone shifts CD timing to match changing reafference. To identify the neural substrates of hormonal CD shifts, we treated Brienomyrus brachyistius with testosterone and recorded field potentials from six nuclei linking electromotor, CD, and electrosensory pathways. Testosterone delayed and elongated field potentials in the mesencephalic command-associated nucleus (MCA) of the CD pathway, which shifted downstream activity. We identified substrates of evolutionary and age-related shifts in two species of Campylomormyrus with dramatically different EODs: one with short-duration EODs and one with long EODs that can elongate as individuals age. Both inter- and intraspecies EOD variation was associated with the onset and duration of MCA field potentials. We find distinct processes-hormonal plasticity over days, age-related changes over years, and evolutionary divergence-converge on a common substrate to synchronize CD with reafference. This suggests that sensorimotor systems can evolve a shared solution for temporal coordination across timescales.