Neuroscience
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Dopaminergic projections to the forebrain arising from the mesencephalic ventral tegmentum modulate information processing in cortical and limbic sites. The lateral hypothalamus is crucial for the coordination of behavioral responses to interoceptive cues. The presence of a hypothalamic input to the ventral tegmental area has been known for some time, but the organization of this pathway has received little attention. ⋯ Moreover, axons that were anterogradely labeled from the lateral hypothalamus were seen throughout the ventral tegmental area, and were often in close proximity to the dendrites and somata of dopamine neurons. Dopamine and orexin fibers were found to codistribute in the medial prefrontal cortex; orexin fibers were present in lower density in the medial shell of the nucleus accumbens, and the central and posterior basolateral nuclei of the amygdala. We conclude that the lateral hypothalamic/perifornical projection represents an anatomical substrate by which interoceptive-related signals may influence forebrain dopamine function.
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The aim of this study was to test the hypothesis that under prolonged global ischemic injury, the somatosensory thalamus and the cortex would manifest differential susceptibility leading to varying degrees of thalamo-cortical dissociation. The thalamic electrical responses displayed increasing suppression with longer durations of ischemia leading to a significant thalamo-cortical electrical dissociation. The data also point to a selective vulnerability of the network oscillations involving the thalamic relay and reticular thalamic neurons. ⋯ There was no significant reduction in somatosensory cortical N20 (negative peak in the cortical response at 20 ms after stimulus) amplitude in any of the three groups with asphyxia indicating a thalamo-cortical dissociation in G3. Further, rhythmic spindle oscillations in the thalamic VPL nuclei that normally accompany the ON response recover either slowly after the recovery of ON response (in the case of G1 and G2) or do not recover at all (in the case of G3). We conclude that there is strong evidence for selective vulnerability of thalamic relay neurons and its network interactions with the inhibitory interneurons in the somatosensory pathway leading to a thalamo-cortical dissociation after prolonged durations of global ischemia.
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White matter strips extracted from adult guinea-pig spinal cords were maintained in vitro and studied physiologically using a double sucrose gap technique and anatomically using a horseradish peroxidase assay. The amplitude of compound action potentials was monitored continuously before, during, and after elongation. Three types of conduction blocks resulting from stretch injury were identified: an immediate, spontaneously reversible component, which may result from a transient increase in membrane permeability and consequent disturbance of ionic distribution; a second component that was irreversible within 30-60 min of recording, perhaps resulting from profound axolemmal disruption; and a third component, which may be due to perturbation of the myelin sheath, that was reversible with application of 100 microM of the potassium channel blocker, 4-aminopyridine. ⋯ Further, in the entire length of the cord strip subjected to stretch, axons closer to the surface were found to be more likely to suffer membrane damage, which distinguished stretch injury from compression injury. In summary, we have developed an in vitro model of axonal stretch that provides the ability to monitor changes in the properties of central myelinated axons following stretch injury in the absence of pathological variables related to vascular damage. This initial investigation found no evidence of secondary deterioration of axons in the first 30 min after stretch in vitro, although there was evidence of both transient and lasting physiological and anatomical damage to axons and their myelin sheaths.
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Hypocretin 2 (orexin B) is a hypothalamic neuropeptide thought to be involved in regulating energy homeostasis, autonomic function, arousal, and sensory processing. Neural circuits in the caudal nucleus tractus solitarius (NTS) integrate viscerosensory inputs, and are therefore implicated in aspects of all these functions. We tested the hypothesis that hypocretin 2 modulates fast synaptic activity in caudal NTS areas that are generally associated with visceral sensation from cardiorespiratory and gastrointestinal systems. ⋯ The increase in EPSC frequency persisted in the presence of tetrodotoxin, suggesting a role for the peptide in regulating glutamate release in the NTS by acting at presynaptic terminals. These data suggest that hypocretin 2 modulates excitatory, but not inhibitory, synapses in caudal NTS neurons, including viscerosensory inputs. The selective nature of the effect supports the hypothesis that hypocretin 2 plays a role in modulating autonomic sensory signaling in the NTS.
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CB1 receptors have been localized to primary afferent neurons, but little is known about the direct effect of cannabinoids on these neurons. The depolarization-evoked increase in the concentration of free intracellular calcium ([Ca(2+)](i)), measured by microfluorimetry, was used as a bioassay for the effect of cannabinoids on isolated, adult rat primary afferent neurons 20-28 h after dissociation of dorsal root ganglia. Cannabinoid agonists CP 55,940 (100 nM) and WIN 55,212-2 (1 microM) had no effect on the mean K(+)-evoked increase in [Ca(2+)](i) in neurons with a somal area<800 microm(2), but the ligands attenuated the evoked increase in [Ca(2+)](i) by 35% in neurons defined as intermediate in size (800-1500 microm(2)). ⋯ Modulation of calcium channels is one mechanism by which cannabinoids may decrease transmitter release from primary afferent neurons. An effect on voltage-dependent calcium channels, however, represents only one possible effect of cannabinoids on primary afferent neurons. Identifying the mechanisms by which cannabinoids modulate nociceptive neurons will increase our understanding of how cannabinoids produce anti-nociception in normal animals and animals with tissue injury.