Neuroscience
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The hypothesis that corticocerebellar units projecting to vestibulospinal neurons contribute to the spatiotemporal response characteristics of forelimb extensors to animal displacement was tested in decerebrate cats in which the activity of Purkinje cells and unidentified cells located in the cerebellar anterior vermis was recorded during wobble of the whole animal. This stimulus imposed to the animal a tilt of fixed amplitude (5 degrees) with a direction moving at a constant angular velocity (56.2 degrees/s), both in the clockwise and counterclockwise directions over the horizontal plane. Eighty-three percent (143/173) of Purkinje cells and 81% (42/52) of unidentified cells responded to clockwise and/or counterclockwise rotations. ⋯ It was shown that for each selected time in the tilt cycle the direction of the population vector closely corresponded to that of the head tilt, while its amplitude was related to that of the stimulus. We conclude that the broad distribution of the response vector orientation of units located in the cerebellar anterior vermis represents an appropriate substrate for the cerebellar control of vestibulospinal reflexes involving extensor muscles during a variety of head tilts. In view of their efferent projections to the vestibular and fastigial nuclei, the cerebellar anterior vermis may provide a framework for the spatial coding of vestibular inputs, giving equal emphasis to both side-to-side and fore-aft stability.
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The expression of the novel growth arrest and DNA damage-inducible gene GADD45 was examined in kainate-induced epileptic brain damage in the rat using in situ hybridization, northern blot analysis, western blot analysis and immunocytochemistry. Systemic administration of kainate resulted in DNA damage and neuronal degeneration in vulnerable neurons of limbic regions, including the amygdala and hippocampal pyramidal layers, as shown by in situ DNA nick end-labelling and histological staining. ⋯ GADD45 protein was overexpressed in non-vulnerable neurons up to 72 h after kainate injection. Because GADD45 may participate in the DNA excision repair process and because it has been shown to be overexpressed in neurons that survive focal cerebral ischaemia, these results support the hypothesis that GADD45 may have a protective role in the injured brain.
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Persistent hyperexcitability follows synchronized bursting induced in the CA3 region of hippocampal slices by perfusion with high concentrations (2000 IU/ml) of the GABAA antagonist, penicillin. This hyperexcitable state is characterized by: i) slow recovery from bursting following penicillin washout; ii) persistent "post-burst" field potential oscillations and iii) increased probability of spontaneous bursting with ordinarily sub-convulsant doses of GABAA antagonists. An N-methyl-D-aspartate-independent type of long-term potentiation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate excitatory postsynaptic potentials occurred following bursting. ⋯ This form of long-term potentiation contributed to the network oscillations characteristics of the hyperexcitable state persisting after epileptiform activity but was not sufficient to entirely explain them. Epileptic seizures may engage normal memory mechanisms which increase neuronal excitability and predispose the hippocampal network to further seizures. This may, in part, account for the propensity for hippocampal seizure foci to become intractable.
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In vivo extracellular single-unit recording techniques revealed that chronic cold stress significantly alters both the basal and the evoked electrophysiological activity of noradrenergic neurons in the locus coeruleus of the anaesthetized rat. Following 17-21 days of chronic cold exposure (5 degrees C), the single-unit activity of histologically-identified locus coeruleus neurons in chloral hydrate-anaesthetized rats was recorded and analysed in terms of their basal firing rate and pattern of spike activity, as well as their response to footshock stimulation. ⋯ The evoked spike activity of locus coeruleus cells in cold-stressed rats also differed significantly from that of control rats along two dimensions: i) they were more likely to respond to footshock stimulation (mean = 90.3% vs 74.4%, respectively); and ii) these responses were more likely to consist of multispike bursts of action potentials (mean = 8 bursts/50 stimulations vs 1 burst/50 stimulations, respectively). These results indicate that alterations in the electrophysiological activity of noradrenergic locus coeruleus neurons may contribute to the phenomenon of stress-induced sensitization of norepinephrine release that is thought to underlie some of the neuropathological changes that accompany long-term stress.
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Sucrose gap recordings from the dorsal roots of isolated, hemisected frog spinal cords were used to determine the effects of metabotropic L-glutamate receptor activation on primary afferent terminals by (+/-)-1-amino-trans-1,3-cyclopentane-dicarboxylic acid (t-ACPD). Dorsal root potentials evoked by ventral root volleys were significantly reduced by t-ACPD (30 microM), as were GABA- and muscimol-induced afferent terminal depolarizations. The effects of t-ACPD on GABA-depolarizations depended upon activation of group I metabotropic glutamate receptors, i.e. the effects were blocked by the group I/II antagonist (RS)-alpha-methyl-4-carboxyphenylglycine, but not by the group II antagonist alpha-methyl-(2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine or the group III antagonist alpha-methyl-(S)-2-amino-4-phosphonobutyrate and were mimicked by the group I agonist 3,5-dihydroxyphenylglycine but were not mimicked by the group III agonist (S)-2-amino-4-phosphonobutyrate. ⋯ Low concentrations of N-methyl-D-aspartate (10 microM) mimicked the effect of t-ACPD on GABA responses. These results suggest that t-ACPD's depression of GABA depolarizations involves an indirect, three-stage mechanism that includes activation of Group I metabotropic glutamate receptors on interneurons and/or on afferent terminals, the release of L-glutamate from the latter structures, and the activation of N-methyl-D-aspartate receptors on primary afferent terminals. The depression of GABA depolarizations caused by the release of L-glutamate from afferent terminal and/or interneurons leads to a block of presynaptic inhibition (produced in the frog spinal cord by GABA) resulting in a positive feed-forward amplification of reflex transmission.