Neuroscience
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The use of deep brain stimulation (DBS) as an effective clinical therapy for a number of neurological disorders has been greatly hindered by the lack of understanding of the mechanisms which underlie the observed clinical improvement in patients. This problem is confounded by the difficulty of investigating the neuronal effects of DBS in situ, and the impossibility of measuring the induced current in vivo. In our recent computational work using a quasi-static finite element (FEM) model we have quantitatively shown that the properties of the depth electrode-brain interface (EBI) have a significant effect on the electric field induced in the brain volume surrounding the DBS electrode. ⋯ Results showed that the EBI affected the waveform shaping differently at different post-implantation stages, and that this in turn had implications on induced current distribution across the EBI. Furthermore, we investigated whether hypothetical waveforms, which were shown to have potential usefulness for neural stimulation but are not yet applied clinically, would have any advantage over the currently used square pulse. In conclusion, the influence of reactivity of the EBI on the crossing stimulation current in therapeutic DBS is significant, and affects the predictive estimation of current distribution around the implanted DBS electrode in the human brain.
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Comparative Study
Robust axonal growth and a blunted macrophage response are associated with impaired functional recovery after spinal cord injury in the MRL/MpJ mouse.
Spinal cord injury (SCI) in mammals leads to a robust inflammatory response followed by the formation of a glial and connective tissue scar that comprises a barrier to axonal regeneration. The inbred MRL/MpJ mouse strain exhibits reduced inflammation after peripheral injury and shows true regeneration without tissue scar formation following an ear punch wound. We hypothesized that following SCI, the unique genetic wound healing traits of this strain would result in reduced glial and connective tissue scar formation, increased axonal growth, and improved functional recovery. ⋯ Close examination of the chronic lesion site revealed evidence of ongoing degeneration both within and surrounding the lesion site. Thus, the regenerative genetic wound healing traits of the MRL/MpJ mice contribute to the evolution of a lesion environment that supports enhanced axon growth after SCI. However, this response occurs at the expense of meaningful functional recovery.
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Oscillatory activity is a prominent characteristic of electrophysiological recordings in the olfactory system and has been proposed to play a key role in encoding olfactory representations. Studies in several systems have shown that some aspects of information coding involve characteristics that intertwine spikes and fast oscillations (in the beta and gamma range) of local field potentials (LFP). In the insect olfactory system, it has been proposed that oscillatory activity could provide a temporal link between cells. ⋯ Our results suggest that gamma oscillation may act as a temporal filter. Oscillatory phase-coupled spikes in the OB could act in increasing the probability of spike emission in the aPC cell during a narrow time-window, explaining the tight phase-coupling observed in the aPC. The role of spike-LFP phase-coupling as a binding function between odor features is discussed.
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The protein fragment nesfatin-1 was recently implicated in the control of food intake. Central administration of this fragment results in anorexia and reduced body weight gain, whereas antisense or immunological nesfatin-1 antagonism causes increased food intake and overweight. Nesfatin-1 is derived from the precursor nucleobindin-2 (NUCB2). ⋯ Furthermore, nesfatin was extensively colocalized with cocaine- and amphetamine-regulated transcript in almost all NUCB2-expressing brain regions. These data reveal a wider distribution of NUCB2/nesfatin-1 than previously known, suggesting that the metabolic actions of this protein may involve not only feeding behavior but also endocrine and autonomic effects on energy expenditure. In addition, the subcellular distribution of nesfatin-like immunoreactivity indicates that this protein may not be processed like a conventional secreted neuromodulator.
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To understand plastic changes in the dorsal horn related to neuropathic pain, we developed a model of decompression in rats with chronic constriction injury (CCI) and investigated corresponding changes in the dorsal horn. At postoperative week 4 (POW 4) of CCI, rats were divided into a decompression group, in which ligatures were removed, and a CCI group, in which ligatures remained. Spinal cords were immunostained for substance P (SP), the delta-opioid receptor (DOR), and calcitonin gene-related peptide (CGRP). ⋯ In the CCI group, neuropathic pain behaviors became normalized at POW 12 with corresponding changes in dorsal horn indexes for both SP and DOR similar to those of the decompression group. In contrast, changes in the dorsal horn indexes of CGRP were similar in both the CCI and decompression groups throughout the experimental period. These findings suggest that CCI and decompression cause different patterns in peptidergic and DOR (+) nerve terminals in the dorsal horn.