Neuroscience
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Comparative Study
Modulation of electrically evoked acetylcholine release through cannabinoid CB1 receptors: evidence for an endocannabinoid tone in the human neocortex.
Cannabinoids are known to inhibit neurotransmitter release in the CNS through CB1 receptors. The present study compares the effects of synthetic cannabinoids on acetylcholine (ACh) release in human and mice neocortex. We further investigated a possible endocannabinoid tone on CB1 receptors in human neocortex caused by endogenous agonists like anandamide or 2-arachidonylglycerol. ⋯ The results show that activation of CB1 cannabinoid receptors leads to inhibition of ACh release in the human and mouse neocortex. The endocannabinoid tone is high in the human, but not in the mouse neocortex and is dependent on neuronal activity. SR141716 acts as a competitive CB1 receptor antagonist.
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Comparative Study
Association of gephyrin and glycine receptors in the human brainstem and spinal cord: an immunohistochemical analysis.
Gephyrin is a postsynaptic clustering molecule that forms a protein scaffold to anchor inhibitory neurotransmitter receptors at the postsynaptic membrane of neurons. Gephyrin was first identified as a protein component of the glycine receptor complex and is also colocalized with several GABAA receptor subunits in rodent brain. We have studied the distribution of gephyrin and glycine receptor subunits in the human brainstem and spinal cord using immunohistochemistry at light and confocal laser scanning microscopy levels. ⋯ Colocalization of immunoreactivities for gephyrin and glycine receptor subunits was detected in the dorsal and ventral horns of the spinal cord, the hypoglossal nucleus and the medial vestibular nucleus of the medulla. The results clearly establish that gephyrin is ubiquitously distributed and is colocalized, with a large proportion of glycine receptor subunits in the human brainstem and spinal cord. We therefore suggest that gephyrin functions as a clustering molecule for major subtypes of glycine receptors in the human CNS.
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Comparative Study
In vivo and in vitro effects of peripheral galanin on nociceptive transmission in naive and neuropathic states.
Galanin is widely distributed in the nervous system and is consistently upregulated in both dorsal root ganglion and spinal neurones by peripheral nerve injury. This study investigates the peripheral effects of galanin on nociceptive neurones using in vitro and in vivo electrophysiological techniques in naive and neuropathic rats. Using an in vitro skin-nerve preparation recording from single nociceptive fibres, galanin (1 microM) significantly inhibited firing induced by noxious heat in 65% of fibres examined. ⋯ Injection of galanin (0.1-10 microg) into hindpaw receptive fields inhibited responses to innocuous mechanical, noxious mechanical and noxious heat stimuli in a proportion of neurones in each animal group and facilitated the remaining neurones. However, a higher proportion of neurones (80-90%) was inhibited by peripheral galanin administration in SNL rats compared with naive (45-55%) and sham (70-80%) rats. These results show that galanin can have both excitatory and inhibitory effects on peripheral sensory neurones, perhaps reflecting differential receptor activation, and that the proportion of these receptors may change following peripheral neuropathy.
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Comparative Study
Serotonergic serotonin (1A) mixed agonists/antagonists elicit large-magnitude phase shifts in hamster circadian wheel-running rhythms.
The biological clock that generates circadian rhythms in mammals is located within the suprachiasmatic nuclei at the base of the hypothalamus. The circadian clock is entrained to the daily light/dark cycle by photic information from the retina. The retinal input to the clock is inhibited by exogenously applied serotonin agonists, perhaps mimicking an endogenous inhibitory serotonergic input to the clock arriving from the midbrain raphe. ⋯ These results suggest that pharmacologically blocking raphe input to the suprachiasmatic circadian clock results in substantially larger photically induced phase advances in wheel-running rhythms. This is further evidence that raphe input to the circadian clock is probably acting to dampen the clock's response to light under certain conditions. The large-magnitude phase shifts, and temporal-activity profile seen with BMY 7378 and S 15535, suggest that compounds with this unique pharmacological profile may be beneficial in the treatment of circadian phase delays recently reported to be a complication resulting from Alzheimer's disease.
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Comparative Study
Intrinsic collaterals of layer 6 Meynert cells and functional columns in primate V1.
Meynert cells are a distinct type of large neuron which project to area MT/V5 and to subcortical targets, including the superior colliculus. They have recently been shown to have extensive intrinsic collaterals spreading up to 8.0 mm within layer 6 of area V1 [J Comp Neurol 441 (2001) 134]. Using intrinsic signal imaging combined with tracer injections, this study investigates how Meynert cell collaterals are mapped in relation to the functional architecture of area V1 in macaque monkeys. ⋯ This contrasts with the same-eye bias previously reported for intrinsic collaterals of pyramidal neurons in layer 3. The suggestion is that the system of Meynert intrinsic collaterals is involved with binocular interactions over wide sectors of the visual field. This might be related to processes such as optic flow or, especially given the wide-field spread, even contour completion or interpolation.