This study was aimed at to investigating the protective effect of a combined treatment with glial cell line derived neurotrophic factor (GDNF) and neurotrophin 3 (NT 3) on noise induced outer hair cell (OHC) damage. Guinea pigs were subjected to receiving infusion of an artificial perilymph containing GDNF (100ng/ml) and NT 3 (2 5?g/ml) into one cochlea via a mini osmotic pump. Three days later, the animals were exposed to a 4kHz narrow band noise at 115 dB SPL for 4h. The control animals received the same treatment except GDNF and NT 3. Thresholds of auditory brainstem responses (ABRs), elicited by clicks, were measured before and 3 days after the surgery of the pump implantation, and 10 days following noise exposure. Then, the subjects were sacrificed and the cochleas were stained with Hoechst 33342. The specimens were examined under a fluorescence microscope for quantitative assessment of the OHC nuclear morphology. The results showed that compared with the control animals, the drug treated ones had significant less swollen OHC nuclei ( P

To observe the morphological changes in hair cell nuclei in guinea pigs following noise exposure, guinea pigs were exposed to 4 kHz narrow band noise at 115 dB SPL for 4h. The cochleae were collected for the examination of the hair cell nuclei 14 days after the noise exposure. A fluorescent dye, Hoechst 33342,a fluorescent dye, was used to label the nuclear DNA and the specimens were examined under a fluorescence microscope for quantitative assessment of hair cell nuclear damage. There were three types of morphological changes in the damaged hair cell nuclei: nuclear swelling, nuclear condensation (karyopyknosis) and nuclear missing. Nuclear swelling was more frequent than nuclear missing. Nuclear condensation was less frequently found. The results suggested that complicated, long term and non synchronous biological processes might be involved in noise induced hair cell damage. A large number of hair cells with swollen nuclei, which might recover afte wards,still could be seen in the cochlea two weeks after noice exposure.

Cerebellar malfunction can lead to sleep disturbance such as excessive daytime sleepiness, suggesting that the cerebellum may be involved in regulating sleep and/or wakefulness. However, understanding the features of cerebellar regulation in sleep and wakefulness states requires a detailed characterization of neuronal activity within this area. By performing multiple-unit recordings in mice, we showed that Purkinje cells (PCs) in the cerebellar cortex exhibited increased firing activity prior to the transition from sleep to wakefulness. Notably, the increased PC activity resulted from the inputs of low-frequency non-PC units in the cerebellar cortex. Moreover, the increased PC activity was accompanied by decreased activity in neurons of the deep cerebellar nuclei at the non-rapid eye-movement sleep-wakefulness transition. Our results provide in vivo electrophysiological evidence that the cerebellum has the potential to actively regulate the sleep-wakefulness transition.

The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCN^Vm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCN^Vm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCN^Vm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCN^Vm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCN^Vm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCN^Vm neurons' function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.
Animals ; Blinking ; Cerebellar Nuclei/physiology* ; Cerebellum ; Mice ; Neurons/physiology* ; Thalamus