Neuroscience
-
Fifteen percent to 35% of the United States population experiences tinnitus, a subjective "ringing in the ears". Up to 10% of those afflicted report severe and disabling symptoms. Tinnitus was induced in rats using unilateral, 1 h, 17 kHz-centered octave-band noise (116 dB SPL) and assessed using a gap-startle method. ⋯ Consistent with decreased alpha(1) subunit protein levels, strychnine binding studies showed significant tinnitus-related decreases in the number of GlyR binding sites, supporting tinnitus-related changes in the number and/or composition of GlyRs. Collectively, these findings suggest the development of tinnitus is likely associated with functional GlyR changes in DCN fusiform cells consistent with previously described behavioral and neurophysiologic changes. Tinnitus related GlyR changes could provide a unique receptor target for tinnitus pharmacotherapy or blockade of tinnitus initiation.
-
Recent studies have indicated a role for the endocannabinoid system in the behavioral and physiological effects of alcohol (ethanol), particularly ethanol seeking behaviors. However, its role in modulating binge-like intake and/or the mechanism by which it may exert these effects remain poorly understood. The current study used a newly developed strain-specific animal model of binge drinking, dubbed 'Drinking In the Dark' (DID), to determine if facilitation of the endocannabinoid system with the synthetic cannabinoid agonist WIN 55-212,2 (WIN) modulates binge-like ethanol intake in male C57BL/6J (B6) mice. ⋯ Importantly, follow-up studies revealed that in some cases alterations in fluid consumption may have been influenced by competing locomotor activity (or inactivity). The present data are consistent with previous research in that agonism of the endocannabinoid system increases ethanol intake in rodents and implicate the pVTA in the modulation of drinking to intoxication. Moreover, the dose-dependent alterations in locomotor activity emphasize the importance of directly assessing multiple (possibly competing) behaviors when evaluating drug effects on voluntary consumption.
-
Orexin-A, synthesized by neurons of the lateral hypothalamus helps to maintain wakefulness through excitatory projections to nuclei involved in arousal. Obvious changes in eye movements, eyelid position and pupil reactions seen in the transition to sleep led to the investigation of orexin-A projections to visuomotor cell groups to determine whether direct pathways exist that may modify visuomotor behaviors during the sleep-wake cycle. Histological markers were used to define these specific visuomotor cell groups in monkey brainstem sections and combined with orexin-A immunostaining. ⋯ In contrast, the motoneurons supplying the multiply-innervated muscle fibers of the extraocular muscles, the motoneurons of the levator palpebrae muscle in the central caudal nucleus, and especially the preganglionic neurons supplying the ciliary ganglion received a strong orexin input. We interpret these results as evidence that orexin-A does modulate pupil size, lid position, and possibly convergence and eye alignment via the motoneurons of multiply-innervated muscle fibres. However orexin-A does not directly modulate premotor pathways for saccades or the singly-innervated muscle fibre motoneurons.
-
The supplementary motor area (SMA) is thought to contribute to the generation of anticipatory postural adjustments (APAs, which act to stabilize supporting body segments prior to movement), but its precise role remains unclear. In addition, participants with Parkinson's disease (PD) exhibit impaired function of the SMA as well as decreased amplitudes and altered timing of the APA during step initiation, but the contribution of the SMA to these impairments also remains unclear. To determine how the SMA contributes to generating the APA and to the impaired APAs of participants with PD, we examined the voluntary steps of eight participants with PD and eight participants without PD, before and after disrupting the SMA and dorsolateral premotor cortex (dlPMC), in separate sessions, with 1-Hz repetitive transcranial magnetic stimulation (rTMS). ⋯ Peak amplitudes of the APAs were unaffected by rTMS to either site. The symptom severity of the participants with PD positively correlated with the extent that rTMS over the SMA affected the durations of their APAs. The results suggest that the SMA contributes to the timing of the APA and that participants with PD exhibit impaired timing of their APAs, in part, due to progressive dysfunction of circuits associated with the SMA.
-
Plasticity in the adult mammalian brain can occur after damage to peripheral nerves and has also been described in the auditory system. Acoustic trauma, resulting in a loss of cochlear sensitivity, can lead to elevated levels of spontaneous activity, that is hyperactivity, in central nuclei such as the inferior colliculus. The current view is that this hyperactivity is centrally generated as a result of altered input. ⋯ This was accompanied by hyperactivity in restricted frequency areas of the inferior colliculus, broadly corresponding to the cochlear threshold loss. We found that hyperactivity in the inferior colliculus depended on neural activity in the cochlea at all recovery times, since it disappeared after cochlear ablation and treatments blocking spontaneous firing of primary afferents. We suggest that the dependency of the central hyperactivity on the integrity of the peripheral receptor indicates hyperexcitability within the CNS resulting in greater neuronal firing in response to normal levels of peripheral spontaneous activity.