Neuroscience
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Previous findings suggest that neuroadaptations downstream of D-1 dopamine (DA) receptor stimulation in nucleus accumbens (NAc) are involved in the enhancement of drug reward by chronic food restriction (FR). Given the high co-expression of D-1 and GluR1 AMPA receptors in NAc, and the regulation of GluR1 channel conductance and trafficking by D-1-linked intracellular signaling cascades, the present study examined effects of the D-1 agonist, SKF-82958, on NAc GluR1 phosphorylation, intracranial electrical self-stimulation reward (ICSS), and reversibility of reward effects by a polyamine GluR1 antagonist, 1-NA-spermine, in ad libitum fed (AL) and FR rats. Systemically administered SKF-82958, or brief ingestion of a 10% sucrose solution, increased NAc GluR1 phosphorylation on Ser845, but not Ser831, with a greater effect in FR than AL rats. ⋯ These results suggest a role of NAc GluR1 in the reward-potentiating effect of D-1 DA receptor stimulation and its enhancement by FR. Moreover, GluR1 involvement appears to occur downstream of D-1 DA receptor stimulation rather than reflecting a basal increase in GluR1 expression or function. Based on evidence that phosphorylation of GluR1 on Ser845 primes synaptic strengthening, the present results may reflect a mechanism via which FR normally facilitates reward-related learning to re-align instrumental behavior with environmental contingencies under the pressure of negative energy balance.
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Spontaneous activity is a well-known neural phenomenon that occurs throughout the brain and is essential for normal development of auditory circuits and for processing of sounds. Spontaneous activity could interfere with sound processing by reducing the signal-to-noise ratio. Multiple studies have reported that spontaneous activity in auditory neurons can be suppressed by sound stimuli. ⋯ Beyond the initial 50 ms period, the absence of significant changes in input resistance during suppression suggests that suppression is presynaptic in origin. Namely, it may occur on presynaptic terminals and/or elsewhere on presynaptic neurons. Suppression of spontaneous firing may serve as a mechanism for enhancing signal-to-noise ratios during signal processing.
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The recently discovered exchange protein directly activated by cAMP (Epac), a guanine exchange factor for the G-protein RAP-1, is directly activated by cAMP independently of protein kinase A (PKA). While cAMP is known to be an important second messenger in the retina, the presence of Epac has not been investigated in this tissue. The goal of the present study was to determine if the Epac1 and Epac2 genes are present and to characterize their location within the retina. ⋯ Uniquely, Epac2 was expressed by cone photoreceptor inner and outer segments, cell bodies, and synaptic terminals. In contrast, Epac1 was expressed in vesicular glutamate transporter 1 (VGlut1) and C-terminal binding protein 2 (CtBP2) positive photoreceptor synaptic terminals. Together, these results provide evidence that Epac1 and Epac2 are differentially expressed within the retina and provide the framework for further functional studies of cAMP pathways within the retina.
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We have previously developed a model in the rat for the transition from acute to chronic pain, hyperalgesic priming, in which a long-lasting neuroplastic change in signaling pathways mediates a prolongation of proinflammatory cytokine-induced nociceptor sensitization and mechanical hyperalgesia, induced at the site of a previous inflammatory insult. Induction of priming is mediated by activation of protein kinase C(epsilon) (PKC(epsilon)) in the peripheral terminal of the primary afferent nociceptor. Given that hyperalgesic mediator-induced PKC(epsilon) translocation occurs in isolectin B4 (IB4)(+)-nonpeptidergic but not in receptor tyrosine kinase (TrkA)(+)-peptidergic nociceptors, we tested the hypothesis that hyperalgesic priming was restricted to the IB4(+) subpopulation of nociceptors. ⋯ Thus, hyperalgesic priming occurs in both the IB4(+)-nonpeptidergic and TrkA(+)-peptidergic subpopulations of nociceptive afferents. Of note, however, while attenuation of PKC(epsilon) prevented NGF-induced priming, the hyperalgesia induced by NGF is PKC(epsilon) independent. We propose that separate intracellular pools of PKC(epsilon), in the peripheral terminals of nociceptors, mediate nociceptor sensitization and the induction of hyperalgesic priming.
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Many neurological diseases result in a severe inability to reach for which there is no proven therapy. Promising new interventions to address reaching rehabilitation using robotic training devices are currently under investigation in clinical trials but the neural mechanisms that underlie these interventions are not understood. Transcranial magnetic stimulation (TMS) may be used to probe such mechanisms quickly and non-invasively, by mapping muscle and movement representations in the primary motor cortex (M1). ⋯ Movement vectors remained relatively constant (limited to <90 degrees section of the planar field) within some subjects across the entire map, while others covered a wider range of directions. This may be due to individual differences in cortical physiology or anatomy, resulting in a practical limit to the areas that are TMS-accessible. This study provides a baseline inventory of possible TMS-evoked arm movements in the robotic reaching trainer, and thus may provide a real-time, non-invasive platform for neurophysiology based evaluation and therapy in motor rehabilitation settings.