Nuclear Factor κb Deficiency is Associated with Auditory Nerve Degeneration and Increased Noise-Induced Hearing Loss

Degeneration of the spiral ganglion neurons (SGNs) of the auditory nerve occurs with age and in response to acoustic injury. Histopathological observations suggest that the neural degeneration often begins with an excitotoxic process affecting the afferent dendrites under the inner hair cells (IHCs), however, little is known about the sequence of cellular or molecular events mediating this excitotoxicity. Nuclear factor κB (NFκB) is a transcription factor involved in regulating inflammatory responses and apoptosis in many cell types. NFκB is also associated with intracellular calcium regulation, an important factor in neuronal excitotoxicity. Here, we provide evidence that NFκB can play a central role in the degeneration of SGNs. Mice lacking the p50 subunit of NFκB (p50−/− mice) showed an accelerated hearing loss with age that was highly associated with an exacerbated excitotoxic-like damage in afferent dendrites under IHCs and an accelerated loss of SGNs. Also, as evidenced by immunostaining intensity, calcium-buffering proteins were significantly elevated in SGNs of the p50−/− mice. Finally, the knock-out mice exhibited an increased sensitivity to low-level noise exposure. The accelerated hearing loss and neural degeneration with age in the p50−/− mice occurred in the absence of concomitant hair cell loss and decline of the endocochlear potential. These results indicate that NFκB activity plays an important role in protecting the primary auditory neurons from excitotoxic damage and age-related degeneration. A possible mechanism underlying this protection is that the NFκB activity may help to maintain calcium homeostasis in SGNs

Classifying Human Audiometric Phenotypes of Age-Related Hearing Loss from Animal Models

This find is registered at Portable Antiquities of the Netherlands with number PAN-0002989

Correlated activity of cortical neurons survives extensive removal of feedforward sensory input

A fundamental property of brain function is that the spiking activity of cortical neurons is variable and that some of this variability is correlated between neurons. Correlated activity not due to the stimulus arises from shared input but the neuronal circuit mechanisms that result in these noise correlations are not fully understood. Here we tested in the visual system if correlated variability in mid-level area V4 of visual cortex is altered following extensive lesions of primary visual cortex (V1). To this end we recorded longitudinally the neuronal correlations in area V4 of two behaving macaque monkeys before and after a V1 lesion while the monkeys fixated a grey screen. We found that the correlations of neuronal activity survived the lesions in both monkeys. In one monkey, the correlation of multi-unit spiking signals was strongly increased in the first week post-lesion, while in the second monkey, correlated activity was slightly increased, but not greater than some week-by-week fluctuations observed. The typical drop-off of inter-neuronal correlations with cortical distance was preserved after the lesion. Therefore, as V4 noise correlations remain without feedforward input from V1, these results suggest instead that local and/or feedback input seem to be necessary for correlated activity

Theta rhythmic neuronal activity and reaction times arising from cortical receptive field interactions during distributed attention

Growing evidence suggests that distributed spatial attention may invoke theta (3–9 Hz) rhythmic sampling processes. The neuronal basis of such attentional sampling is, however, not fully understood. Here we show using array recordings in visual cortical area V4 of two awake macaques that presenting separate visual stimuli to the excitatory center and suppressive surround of neuronal receptive fields (RFs) elicits rhythmic multi-unit activity (MUA) at 3–6 Hz. This neuronal rhythm did not depend on small fixational eye movements. In the context of a distributed spatial attention task, during which the monkeys detected a spatially and temporally uncertain target, reaction times (RTs) exhibited similar rhythmic fluctuations. RTs were fast or slow depending on the target occurrence during high or low MUA, resulting in rhythmic MUA-RT cross-correlations at theta frequencies. These findings show that theta rhythmic neuronal activity can arise from competitive RF interactions and that this rhythm may result in rhythmic RTs potentially subserving attentional sampling

Behavioral and evoked-potential thresholds in young and old Mongolian gerbils (Meriones unguiculatus)

Age-dependent hearing loss has been well documented in gerbils exceeding 2 years of age using physiological methods (e.g. [Mills et al. (1990) Hear. Res. 46, 201-210]). We determined behavioral thresholds for broad-band noise and pure-tone pulses in gerbils as a function of age. Contrary to expectations based on previously published physiological data, we found no significant (broad-band noise and 10 kHz) or only a very small hearing loss (7 dB at 2 kHz) in 30-36-month-old animals. In animals over 3 years of age we observed an increased spread of thresholds and threshold shifts exceeding 20 dB in some individuals. Behavioral thresholds of old gerbils from two breeding colonies (University of Regensburg and Medical University of South Carolina) were similar. Data from individual animals where thresholds were determined physiologically and behaviorally indicate that results from auditory brainstem response measurements show no shift at 18 months while subsequent measurements at 28-29 months revealed age-dependent threshold shifts of 10-15 dB. In contrast, thresholds determined by behavioral methods in these same individuals at 31-33 months of age remained stable

Rhythmic neural spiking and attentional sampling arising from cortical receptive field interactions

Summary: Growing evidence suggests that distributed spatial attention may invoke theta (3-9 Hz) rhythmic sampling processes. The neuronal basis of such attentional sampling is however not fully understood. Here we show using array recordings in visual cortical area V4 of two awake macaques that presenting separate visual stimuli to the excitatory center and suppressive surround of neuronal receptive fields elicits rhythmic multi-unit activity (MUA) at 3-6 Hz. This neuronal rhythm did not depend on small fixational eye movements. In the context of a distributed spatial attention task, during which the monkeys detected a spatially and temporally uncertain target, reaction times (RT) exhibited similar rhythmic fluctuations. RTs were fast or slow depending on the target occurrence during high or low MUA, resulting in rhythmic MUA-RT cross-correlations at at theta frequencies. These findings suggest that theta-rhythmic neuronal activity arises from competitive receptive field interactions and that this rhythm may subserve attentional sampling. Highlights: * Center-surround interactions induce theta-rhythmic MUA of visual cortex neurons * The MUA rhythm does not depend on small fixational eye movements * Reaction time fluctuations lock to the neuronal rhythm under distributed attentio