Journal of neurophysiology
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The group I metabotropic glutamate receptor (mGluR) subtype, mGluR1, is highly expressed on the apical dendrites of olfactory bulb mitral cells and thus may be activated by glutamate released from olfactory nerve (ON) terminals. Previous studies have shown that mGluR1 agonists directly excite mitral cells. In the present study, we investigated the involvement of mGluR1 in ON-evoked responses in mitral cells in rat olfactory bulb slices using patch-clamp electrophysiology. ⋯ ON-evoked responses elicited in the presence of THA-TBOA were significantly reduced or completely blocked by LY341495 or LY367385 (100 microM). These results demonstrate that glutamate transporters tightly regulate access of synaptically evoked glutamate from ON terminals to postsynaptic mGluR1s on mitral cell apical dendrites. Taken together with other findings, the present results suggest that mGluR1s may not play a major role in phasic responses to ON input, but instead may play an important role in shaping slow oscillatory activity in mitral cells and/or activity-dependent regulation of plasticity at ON-mitral cell synapses.
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Peripherally delivered opiates attenuate mechanical and thermal hyperalgesia in experimental models of inflammation, suggesting that activation of peripheral opioid receptors decreases the excitability of nociceptors in inflamed tissues. The current study examines the effects of peripheral morphine sulfate on response properties of sensory neurons in healthy and inflamed skin. Afferent units (185) were isolated from tibial nerve of rats using an in vitro glabrous skin-nerve teased-fiber preparation. ⋯ All morphine-sensitive units were nociceptors from inflamed skin with conduction velocities <1.3 m/s. Morphine effects were concentration-dependent and naloxone-sensitive, indicating that the effects were receptor-mediated. These findings provide direct evidence that morphine acts through peripheral opioid receptors to inhibit the activity of cutaneous nociceptors under conditions of inflammation.
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Early in development, neurons only express NR1/NR2B-containing N-methyl-d-aspartate (NMDA) receptors. Later, NR2A subunits are upregulated during a period of rapid synapse formation. This pattern is often interpreted to indicate that NR2A-containing receptors are synaptic and that NR2B-containing receptors are extrasynaptic. ⋯ Extrasynaptic NR2A-containing receptors were also detected in NR2A(-/-) neurons transfected with full-length NR2A. Truncation of the NR2A C terminus did not eliminate synaptic expression of NR2A-containing receptors. Our results indicate that NR2A- and NR2B-containing receptors can be located in either synaptic or extrasynaptic compartments.
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Clinical Trial
Vibrotactile frequency discrimination in human hairy skin.
The human capacity for vibrotactile frequency discrimination has been compared directly for glabrous and hairy skin regions by means of a two-alternative, forced-choice psychophysical procedure in five subjects. Sinusoidal vibratory stimuli, delivered by means of a 4-mm-diam probe, were first used to obtain detection threshold values for the two skin sites, the finger tip and the dorsal forearm, at four standard frequencies, 20, 50, 100, and 200 Hz. ⋯ Cutaneous local anesthesia produced a marked impairment in vibrotactile detection and discrimination at the low standard frequencies of 20 and 50 Hz but little effect at higher frequencies. In summary, the results reveal, first, a striking similarity in vibrotactile discriminative performance in hairy and glabrous skin despite marked differences in detection thresholds for the two sites, and, second, the results confirm that vibrotactile detection and discrimination in hairy skin depend on superficial receptors at low frequencies but depend on deep, probably Pacinian corpuscle, receptors for high frequencies.
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The paraventricular thalamic nucleus (PVT) receives one of the most dense innervations by hypothalamic hypocretin/orexin (Hcrt) neurons, which play important roles in sleep-wakefulness, attention, and autonomic function. The PVT projects to several loci, including the medial prefrontal cortex (mPFC), a cortical region involved in associative function and attention. To study the effect of Hcrt on excitatory PVT neurons that project to the mPFC, we used a new line of transgenic mice expressing green fluorescent protein (GFP) under the control of the vesicular glutamate-transporter-2 promoter. ⋯ Hcrt-2 actions were stronger than those of Hcrt-1, and the action persisted in TTX and in low calcium/high magnesium artificial cerebrospinal fluid, consistent with direct actions mediated by Hcrt receptor-2. Two mechanisms of Hcrt excitation were found: an increase in input resistance caused by closure of potassium channels and activation of nonselective cation channels. The robust excitation evoked by Hcrt-2 on cortically projecting glutamate PVT neurons could generate substantial excitation in multiple layers of the mPFC, adding to the more selective direct excitatory actions of Hcrt in the mPFC and potentially increasing cortical arousal and attention to limbic or visceral states.