Neuroscience
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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.
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Strabismus in human infants is linked strongly to nasotemporal asymmetries of smooth pursuit, but many features of this co-morbidity are unknown. The purpose of this study was to determine how the duration of early-onset strabismus (or timeliness of repair) affects the severity of pursuit asymmetries in a primate model. ⋯ Binocular decorrelation in primates during an early period of fusion development causes permanent smooth pursuit asymmetries when the duration exceeds the equivalent of 3 months in human. These findings support the conclusion that early correction of infantile strabismus promotes normal development of cerebral gaze pathways.
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SR58611A is a selective beta(3)-adrenoceptor (Adrb3) agonist which has demonstrated antidepressant and anxiolytic properties in rodents. The present study confirmed the detection of Adrb3 mRNA transcript in rodent brain sub-regions and evaluated the effect of SR58611A on serotonergic and noradrenergic transmission in rats and mice in an attempt to elucidate the mechanism(s) underlying these properties. SR58611A (3 and 10 mg/kg, p.o.) increased the synthesis of 5-HT and tryptophan (Trp) levels in several rodent brain areas (cortex, hippocampus, hypothalamus, striatum). ⋯ Repeated administration of SR58611A (10 mg/kg, p.o.) did not modify basal norepinephrine release in rat prefrontal cortex whereas it prevented its tail-pinch stress-induced enhancement similarly to reboxetine (15 mg/kg, p.o.). Finally SR58611A increased the firing rate of noradrenergic neurons in the rat locus coeruleus following systemic (3 mg/kg, i.v.) or local (0.01 and 1 microM) but not chronic (10 mg/kg, p.o.) administration. These results suggest that the anxiolytic- and antidepressant-like activities of SR58611A involve an increase of brain serotonergic and noradrenergic neurotransmissions, triggered by activation of Adrb3s.
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Strongly inwardly rectifying K+ (Kir2) channels are endogenously expressed in rat brains and have recently been used as a tool to reduce the neuronal activity. But little is known about the role of Kir2 channels and the chronic effect of the reduced activity on the intrinsic excitability of neurons. Here we constructed a lentiviral vector that coexpressed Kir2.1 and GFP (LvKir2.1) and infected the vector to the hippocampal slice cultures. ⋯ The reduction of the firing was attributed to the hyperpolarized potential rather than to the shunting effect. These reductions were limited to modest current injections, suggesting that the overexpressed Kir2.1 plays the role of a noise-filter. Moreover, the chronic overexpression of Kir2.1 downregulated the expression of the delayed rectifier potassium current in a homeostatic manner, indicating a usefulness of this viral vector to study the activity-dependent neuronal development.
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Classic neurotransmitter phenotypes are generally predetermined and develop as a consequence of target-independent lineage decisions. A unique mode of target-dependent phenotype instruction is the acquisition of the cholinergic phenotype in the peripheral sympathetic nervous system. A body of work suggests that the sweat gland plays an important role to determine the cholinergic phenotype at this target site. ⋯ We employed cholinergic-specific over-expression of the vesicular acetylcholine transporter (VAChT) in transgenic mice to overcome sensitivity limits in the detection of initial cholinergic sweat gland innervation. We found that VAChT immunoreactive nerve terminals were present around the sweat gland anlage already from the earliest postnatal stages on, coincident selectively at this sympathetic target with tyrosine hydroxylase-positive fibers. Our results provide a new mechanistic model for sympathetic neuron-target interaction during development, with initial selection by the target of pioneering nerve terminals expressing a cholinergic phenotype, and subsequent stabilization of this phenotype during development.