Neuroscience
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While clinical characteristics of diabetic painful neuropathy are well described, the underlying electrophysiological basis of the exaggerated painful response to stimuli, as well as the presence of spontaneous pain, are poorly understood. In order to elucidate peripheral contributions to painful diabetic neuropathy, we quantitatively evaluated the function of C-fibers in a rat model of painful diabetic neuropathy, diabetes induced by the pancreatic beta-cell toxin streptozotocin. While there was no significant effect of diabetes on conduction velocity, mechanical threshold or spontaneous activity, the number of action potentials in response to sustained threshold and suprathreshold mechanical stimuli was significantly increased in the diabetic rats. ⋯ In summary, in an established model of painful diabetic neuropathy in the rat, a subset of C-fibers demonstrated a marked hyper-responsiveness to mechanical stimuli. The subset was also found to have a greater mean conduction velocity than the fibers not demonstrating this hyper-responsivity. The present findings suggest that study of individual neurons in vitro may allow elucidation of the ionic basis of enhanced nociception in diabetic neuropathy.
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We examined the effects of systemic administration of a GABA(B) receptor agonist, baclofen, or antagonist, phaclofen, on the expression of c-Fos protein induced 3h after electrical stimulation of the trigeminal ganglion at low (0.1 mA) or high intensities (1.0 mA) in the urethane-anesthetized rat. In saline-treated rats, 10 min stimulation of the trigeminal ganglion induced c-Fos-immunopositive neurons throughout the full extent of the ipsilateral superficial layers of the trigeminal nucleus caudalis, and dorsal or dorsomedial part of the nuclei rostral to obex (trigeminal nucleus principalis, dorsomedial nucleus of trigeminal nucleus oralis and dorsomedial nucleus of trigeminal nucleus interpolaris). Animals stimulated at 1.0 mA induced a significantly higher number of labeled neurons in all the trigeminal sensory nuclei than animals stimulated at 0.1 mA. ⋯ These results indicate that the expression of c-Fos in the trigeminal sensory nucleus is differentially regulated through GABAB receptors in a manner that is dependent on the nucleus and the type of primary afferents that are activated by different stimulus intensities. Systemic administration of baclofen could inhibit both nociceptive and non-nociceptive sensory activity in the trigeminal sensory nucleus. Systemic administration of phaclofen could enhance nociceptive sensory activity but not non-nociceptive activity.
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The contact with the postsynaptic target induces structural and functional modifications in the serotonergic cell C1 of Helix pomatia. In previous studies we have found that the presence of a non-physiological target down-regulates the number of presynaptic varicosities formed by cultured C1 neurons and has a strong inhibitory effect on the action potential-evoked Ca(2+) influx and neurotransmitter release at C1 terminals. Since a large body of experimental evidence implicates the synapsins in the development and functional maturation of synaptic connections, we have investigated whether the injection of exogenous synapsin I into the presynaptic neuron C1 could affect the inhibitory effect of the wrong target on neurotransmitter release. ⋯ A three-fold increase in the amplitude of the sniffer depolarization with respect to the pre-injection amplitude (190+/-29% increase, n=10, P<0.006) was found 5 min after injection of Ca(2+)/calmodulin-dependent protein kinase II-phosphorylated synapsin I that lasted for about 30 min. No significant change was observed after injection of buffer or dephosphorylated synapsin I. These data indicate that the presence of synapsin I induces a fast increase in neurotransmitter release that overcomes the inhibitory effect of the non-physiological target and suggest that the expression of synapsins may play a role in the modulation of synaptic strength and neural connectivity.
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To investigate the basis of the fluctuating activity present in neocortical neurons in vivo, we have combined computational models with whole-cell recordings using the dynamic-clamp technique. A simplified 'point-conductance' model was used to represent the currents generated by thousands of stochastically releasing synapses. Synaptic activity was represented by two independent fast glutamatergic and GABAergic conductances described by stochastic random-walk processes. ⋯ This procedure successfully recreated several properties of neurons intracellularly recorded in vivo, such as a depolarized membrane potential, the presence of high-amplitude membrane potential fluctuations, a low-input resistance and irregular spontaneous firing activity. In addition, the point-conductance model could simulate the enhancement of responsiveness due to background activity. We conclude that many of the characteristics of cortical neurons in vivo can be explained by fast glutamatergic and GABAergic conductances varying stochastically.
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In urethane-anesthetized rats with body temperature maintained at 39-40 degrees C, electrical stimulation of raphe magnus/pallidus/parapyramidal region within 0.5 mm of the ventral medullary surface reduced arterial blood flow to the tail cutaneous bed (measured with a chronically implanted Doppler ultrasonic flowmeter) from 28+/-5 to 6+/-1 cm/s (P<0.01), without changing mesenteric arterial blood flow, and with only small, variable changes in arterial pressure. Injection of bicuculline (50 pmol in 50 nl) at the same site reduced tail flow from 19+/-2 to 3+/-1 cm/s (P<0.01), again without significantly changing mesenteric flow, but with a moderate increase in arterial pressure. ⋯ The rostral medullary raphe controls the tail cutaneous vascular bed in a relatively selective manner. Our findings add to evidence that raphe magnus/pallidus/parapyramidal neurons are involved in regulating cutaneous blood flow in response to changes in body temperature in the rat.