Journal of neurophysiology
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Recent studies suggest that beta (15-30 Hz) oscillatory activity in the subthalamic nucleus (STN) is dramatically increased in Parkinson's disease (PD) and may interfere with movement execution. Dopaminergic medications decrease beta activity and deep brain stimulation (DBS) in the STN may alleviate PD symptoms by disrupting this oscillatory activity. Depth recordings from PD patients have demonstrated beta oscillatory neuronal and local field potential (LFP) activity in STN, although its prevalence and relationship to neuronal activity are unclear. ⋯ Of particular interest was a significant positive correlation between the incidence of oscillatory neurons and the patient's benefit from dopaminergic medications, but not with baseline motor deficits off medication. These findings suggest that the degree of neuronal beta oscillatory activity is related to the magnitude of the response of the basal ganglia to dopaminergic agents rather than directly to the motor symptoms of PD. The study also suggests that LFP beta oscillatory activity is generated largely within the dorsal portion of the STN and can produce synchronous oscillatory activity of the local neuronal population.
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The effects of the synthetic cannabinoid WIN 55,212-2 on heat-evoked firing of spinal wide dynamic range (WDR) neurons were examined in a rodent model of neuropathic pain. Fifty-eight WDR neurons (1 cell/animal) were recorded from the ipsilateral spinal dorsal horns of rats with chronic constriction injury (CCI) and sham-operated controls. Relative to sham-operated controls, neurons recorded in CCI rats showed elevations in spontaneous firing, noxious heat-evoked responses, and afterdischarge firing as well as increases in receptive field size. ⋯ The effect of intravenous administration of WIN 55,212-2 appears to be centrally mediated because administration of the drug directly to the ligated nerve did not suppress the heat-evoked neuronal activity in CCI rats. Pretreatment with the cannabinoid CB(1) receptor antagonists SR141716A or AM251, but not the CB(2) antagonist SR144528, blocked the effects. These results provide a neural basis for reports of potent suppression by cannabinoids of the abnormal sensory responses that result from nerve injury.
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Suppression of reactions to one noxious stimulus by a spatially distant noxious stimulus is termed heterotopic antinociception. In lightly anesthetized rats, a noxious visceral stimulus, colorectal distension (CRD), suppressed motor withdrawals but not blood pressure or heart rate changes evoked by noxious hindpaw heat. Microinjection of muscimol, a GABA(A) receptor agonist, into raphe magnus (RM) reduced CRD-evoked suppression of withdrawals, evidence that RM neurons contribute to this heterotopic antinociception. ⋯ However, when hindpaw withdrawal suppression was incomplete, RM cell discharge resembled the pattern observed in response to heat alone. We propose that on cells excited by CRD facilitate responses to CRD itself, which in turn augments excitation of off cells that then act to suppress cutaneous nociception. RM cells may thereby contribute to the dominance of quiet recuperative reactions evoked by potentially life-threatening visceral stimuli over transient somatomotor activity elicited by less-injurious noxious cutaneous stimuli.
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As in neocortex and hippocampus, neurons in the dorsal horn of the spinal cord develop long-term potentiation of synaptic efficacy (LTP) on high-frequency stimulation (HFS) of their afferent input, although how long LTP lasts in this nociceptive relay nucleus has not yet been addressed. Here we studied neurogenic hyperalgesia, a perceptual correlate of nociceptive LTP, in 13 healthy subjects, after HFS (5 x 1 s at 100 Hz) of superficial cutaneous afferents. ⋯ Touch-evoked pain (dynamic mechanical allodynia) developed in eight of 13 subjects, decayed with a t(1/2) of 2.9 h from the maximum and disappeared within 9.3 h. These findings suggest that a single HFS session induces nociceptive LTP in healthy subjects that corresponds to early-LTP (LTP1), implying primarily posttranslational mechanisms for this type of plasticity of human pain perception.
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Recent work suggests neurons can have different types of gamma-aminobutyric acid type A (GABA(A)) receptors that mediate phasic inhibitory postsynaptic currents (IPSCs) and tonic currents. This study examines the diversity of GABAergic synaptic currents in parasympathetic cardioinhibitory neurons that receive rhythmic bursts of GABAergic neurotransmission. Focal application of gabazine (25 microM) to cardiac vagal neurons in vitro did not change the frequency of firing in spontaneously active neurons or the resting membrane potential; however, picrotoxin (100 microM) significantly depolarized cardiac vagal neurons and increased their firing. ⋯ NO-711 did not significantly alter the holding current in these neurons. The benzodiazepine flunitrazepam (1 microM) significantly increased the tonic current and GABAergic IPSC decay time; surprisingly, however, in the presence of gabazine flunitrazepam failed to elicit any change. These results suggest cardiac vagal neurons possess gabazine-sensitive GABA(A) receptors that mediate phasic synaptic currents, a gabazine-insensitive but picrotoxin-sensitive extrasynaptic tonic current that when blocked depolarizes and increases the firing rate of cardiac vagal neurons, and benzodiazepines recruit a third type of GABA(A) receptor that is sensitive to gabazine and augments the extrasynaptic tonic current.