Neuroscience
-
Tinnitus often occurs after exposure to loud noise. This raises the question of whether repeated exposure to noise increases the risk of developing tinnitus. We thus studied tinnitus development after repeated acoustic overstimulation using startle and auditory brainstem-response techniques applied to Mongolian gerbils. ⋯ The frequency distribution of tinnitus-related changes ranged from 4 to 20 kHz. In the group with the narrow-band noise (0.25 oct) changes center at one frequency range from 10 to 12 kHz. In the group with the broader noise band (0.5 oct), however, two peaks at 8-10 kHz and at 16-18 kHz were found, which suggests that different mechanisms underlie the tinnitus development.
-
The present study tested the hypothesis that exposure to in vitro hypoxia-ischemia alters membrane properties and excitability as well as excitatory synaptic transmission of CA1 pyramidal neurons in the neonatal mouse. ⋯ These results indicate that in vitro ischemia leads to changes in membrane excitability mediated by sodium and potassium channels. Further, it results in enhanced neurotransmitter release from presynaptic terminals. These changes are likely to represent one of the mechanisms of hypoxia/ischemia-mediated seizures in the neonatal period.
-
Treatment of Parkinson's disease (PD) with dopamine replacement relieves symptoms of poverty of movement, but often causes drug-induced dyskinesias. Accumulating clinical and pre-clinical evidence suggests that the primary motor cortex (M1) is involved in the pathophysiology of PD and that modulating cortical activity may be a therapeutic target in PD and dyskinesia. However, surprisingly little is known about how M1 neurotransmitter tone or gene expression is altered in PD, dyskinesia or associated animal models. ⋯ M1 expression of two immediate-early genes (c-Fos and ARC) was strongly enhanced by either L-DOPA or SKF81297. At the same time, expression of genes specifically involved in glutamate and GABA signaling were either modestly affected or unchanged by lesion and/or treatment. We conclude that M1 neurotransmission and signal transduction in the rat 6-OHDA model of PD/dyskinesia mirror features of human PD, supporting the utility of the model to study M1 dysfunction in PD and the elucidation of novel pathophysiological mechanisms and therapeutic targets.
-
Brain-derived neurotrophic factor (BDNF) is abundantly expressed by both developing and adult rat visceral sensory neurons from the nodose ganglion (NG) in vivo and in vitro. We have previously shown that BDNF is released from neonatal NG neurons by activity and regulates dendritic development in their postsynaptic targets in the brainstem. The current study was carried out to examine the cellular and molecular mechanisms of activity-dependent BDNF expression in neonatal rat NG neurons, using our established in vitro model of neuronal activation by electrical field stimulation with patterns that mimic neuronal activity in vivo. ⋯ Electrical stimulation-evoked BDNF expression was inhibited by pretreating neurons with the blocker of voltage-gated sodium channels tetrodotoxin and by removing extracellular calcium. Moreover, our data show that repetitive stimulation-evoked BDNF expression requires calcium influx through N-, but not L-type, channels. Together, our study reveals novel mechanisms through which electrical activity stimulates de novo synthesis of BDNF in sensory neurons, and points to the role of N-type calcium channels in regulating BDNF expression in sensory neurons in response to repetitive stimulation.
-
The perception of tool-object pairs involves understanding their action-relationships (affordances). Here, we sought to evaluate how an observer visually encodes tool-object affordances. Eye-movements were recorded as right-handed participants freely viewed static, right-handed, egocentric tool-object images across three contexts: correct (e.g. hammer-nail), incorrect (e.g. hammer-paper), spatial/ambiguous (e.g. hammer-wood), and three grasp-types: no hand, functional grasp-posture (grasp hammer-handle), non-functional/manipulative grasp-posture (grasp hammer-head). ⋯ Unlike the functional grasp-posture, the manipulative grasp-posture caused the greatest disruption in the object-oriented priming effect, ostensibly as it does not afford tool-object action due to its non-functional interaction with the operant tool-end that actually engages with the object (e.g., hammer-head to nail). The enhanced attention towards the manipulative grasp-posture may serve to encode grasp-intent. Results here shed new light on how an observer gathers action-information when evaluating static tool-object scenes and reveal how contextual and grasp-specific affordances directly modulate visuospatial attention.