Neuroscience
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The capacity of a calpain inhibitor to reduce losses of neurofilament 200-, neurofilament 68- and calpain 1-mediated spectrin breakdown products was examined following traumatic brain injury in the rat. Twenty-four hours after unilateral cortical impact injury, western blot analyses detected neurofilament 200 losses of 65% (ipsilateral) and 36% (contralateral) of levels observed in naive, uninjured rat cortices. Neurofilament 68 protein levels decreased only in the ipsilateral cortex by 35% relative to naive protein levels. ⋯ Morphological protection included preservation of dendritic structure and reduction of axonal retraction balls. In addition, histopathological studies employing hematoxylin and eosin staining indicated reduced extent of contusion at the injury site. These data indicate that calpain inhibitors could represent a viable strategy for preserving the cytoskeletal structure of injured neurons after experimental traumatic brain injury in vivo.
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The control of suckling-induced bursting activity of oxytocin neurons and of phasic activity of vasopressin neurons by N-methyl-D-aspartate receptors was investigated in anaesthetized lactating rats. Receptor antagonist or agonist was applied in the vicinity of supraoptic neurons recorded extracellularly. The basal activity of oxytocin neurons was tonically decreased and increased by sustained application of the antagonist and agonist respectively. ⋯ These results provide evidence that functional N-methyl-D-aspartate receptors regulate the excitability of both oxytocin and vasopressin neurons in lactating rats. These receptors play a paramount role in maintaining a certain level of basal activity which will favour appropriate discharge patterns, tonic for oxytocin neurons and phasic for vasopressin neurons. For oxytocin neurons, this sustained control by ambient glutamate influences the amplitude of bursts, but N-methyl-D-aspartate receptors are probably not involved in the generation of the bursting pattern.
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Among the pathological processes initiated by traumatic brain injury are excessive neuroexcitation and target cell deafferentation. The current study examines the contribution of these injury components, separately as well as their combined effect, on postinjury alterations in the capacity for long-term potentiation and the immunolocalization of N-methyl-D-aspartate receptors and GABA. Adult rats underwent central fluid percussion traumatic brain injury, electrolytic bilateral entorhinal cortex lesions, or a combined injury of both procedures separated by 24 h. ⋯ Both N-methyl-D-aspartate receptor and GABA immunobinding following combined injuries were also reduced relative to those observed following entorhinal lesions alone. The present results suggest that a process of receptor plasticity, possibly involving reactive synaptogenesis, may contribute to postdeafferentation enhancements of long-term potentiation, and that a traumatic brain insult will attenuate these enhancements. This interaction of different injury components suggests that recovery of function following brain injury may be enhanced by pharmacological reduction of neuroexcitation during postinjury intervals of reactive receptor plasticity.
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In the present study we examined whether depletion of dopamine in the medial prefrontal cortex alters the neurochemical activity of mesoaccumbens dopamine neurons and/or their behavioral correlate, motor behavior. Infusion of 6-hydroxydopamine (1 microgram) into the medial prefrontal cortex of rats pretreated with a norepinephrine uptake blocker produced a 70% loss of tissue dopamine, with relative sparing of the norepinephrine content (-23%) in that region. Using in vivo microdialysis, we monitored basal and evoked extracellular dopamine in the nucleus accumbens core and shell of control and lesioned rats. ⋯ These data demonstrate that mesocortical dopamine neurons influence (i) amphetamine-induced dopamine efflux in the nucleus accumbens core and (ii) stress-evoked dopamine efflux in the nucleus accumbens shell. It has been proposed that a disruption in the interaction between cortical and subcortical dopamine neurons is involved in the pathophysiology of schizophrenia. The present data raise the possibility that a disruption in the interaction between mesocortical dopamine neurons and dopamine neurons projecting to the nucleus accumbens shell is involved in those symptoms of schizophrenia that are influenced by stress.
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Whole-cell patch-clamp recordings were made from neurons in the substantia gelatinosa of adult rat spinal cord slices with attached dorsal root to study a slow synaptic current evoked by focal or dorsal root stimulation. Repetitive focal stimulation with a monopolar electrode positioned within substantia gelatinosa elicited a slow excitatory postsynaptic current preceded by a fast excitatory postsynaptic current in 73 of 83 neurons. A similar slow excitatory postsynaptic current was also elicited by stimulation of A delta afferent fibres. ⋯ These observations suggest that a transmitter released from interneurons or descending fibres which are activated in part by A delta afferents, mediates a slow excitatory postsynaptic currents in substantia gelatinosa neurons and that an excitatory amino acid is implicated in the generation of the slow excitatory postsynaptic current, although the receptor appears to differ from the known ligand-gated channels. C afferents are unlikely to contribute to the slow excitatory postsynaptic current. This slow synaptic response may participate in the pain pathway and play an important role in the processing of nociceptive information in the spinal dorsal horn.