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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The temporal sequence of electrophysiological and biochemical correlates of epilepsy induced by systemic injection of kainic acid (15 mg/kg i.p.) was investigated in male rats. A significant decrease in the hippocampal concentration of glutamate and aspartate was observed 20 min after the injection. These decreases preceded both electrographic and behavioral manifestations of epilepsy, thus suggesting a causal relationship between acidic amino acid changes and the genesis of kainate-induced hyperactivity. About 30-45 min after kainate injection, a decrease in glutamate, aspartate, glycine and taurine and no change in GABA concentration were observed. Bioelectrical activity, recorded in the regio inferior (CA3) of the hippocampus or in the fascia dentata revealed the presence of high frequency bursts separated by a long-lasting depression of discharge. About 55-75 min after the injection, the number of spikes in each burst increased and the duration and frequency of interictal pauses decreased. This stage was characterized by a decrease in glutamate and aspartate, restoration to normal of glutamine, glycine and taurine and a decrease in GABA.
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PMID:Altered time course of changes in the hippocampal concentration of excitatory and inhibitory amino acids during kainate-induced epilepsy. 647 26

Study of immature rabbit hippocampus, using the in vitro slice preparation, has revealed seizure-like spreading depression (SD) episodes in tissue from 8-12-day-old animals. These SDs occur both spontaneously and in response to stimulation, and are seen in both extracellular and intracellular recordings. At the cellular level, SDs are similar to epileptiform ictal phenomena in their onset bursts of action potentials, prolonged membrane depolarizations, and afterdischarge bursts. Glial recordings indicate that a large rise in [K+]0 occurs during these SD episodes. Low chloride concentration in the bathing medium facilitates SD occurrence. The immature CA1 region, where inhibition is slow to develop, is more susceptible to SDs than the CA3 region, where inhibitory post-synaptic potentials are potent early in development. These observations suggest that the slice preparation of immature rabbit hippocampus may provide a useful model in which to study epileptiform mechanisms, such as inhibitory efficacy and extracellular potassium clearance, which might be responsible for ictal onset and control.
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PMID:Seizure-like spreading depression in immature rabbit hippocampus in vitro. 673 37

Intrahippocampal infusion of nanogram amounts of the neurotoxin kainic acid were used to investigate possible relationships between the convulsive and the local neurodegenerative properties of the amino acid. Bilateral hippocampal depth electrodes and cortical leads were employed to provide simultaneous and continuous electroencephalographic records following kainate injection in unanesthetized freely-behaving rats. In every animal, morphological analysis was performed 3-5 days after administration of kainic acid and attempts were made to correlate neuronal destruction with electroencephalographic patterns. Doses as low as 500 pg kainate led to behavioral sequelae consisting of grooming, scratching and enhanced locomotor activity. In a roughly dose-dependent fashion (range 500 gp-250 ng), these behaviors increased in frequency and at the highest doses the rats also displayed wet-dog shakes, stereotype mouth movements and occasional facial myoclonus. Apart from these automatisms, generalized motor seizures were never seen. Following kainic acid, a spectrum of electroencephalographic changes could occur consisting of one or more of the following: high voltage fast activity, slow and fast high voltage spiking, paroxysmal bursts, spindle bursts or postictal depression periods. The combination of any two of these changes were defined as an ictal episode if they occurred in all four leads simultaneously. Upon morphological examination, only the highest dose used (250 ng) resulted reliably in the degeneration of CA3, CA4 and, partly, CA1 pyramidal cells on the injected side. While the duration of electroencephalographic changes at this dose was significantly higher than at any of the lower doses, the number of seizures or the total time spent in seizures was not different at 250 ng from that at 50 ng. At the latter dose, however, only marginal cell damage could be found. Our data indicate that very low doses of kainic acid directly applied to hippocampal CA3 neurons, can elicit bilateral changes in the electroencephalogram indicative of repetitive limbic seizures which are not necessarily accompanied by neuronal degeneration. At higher doses (250 ng), kainic acid treatment results in both seizure activity and nerve cell death but the two effects appear mechanistically unrelated. While there is no clear-cut dose-response relationship between neuronal damage and seizures, extended electroencephalographic changes of a 15-30 Hz fast activity or simple spiking phenomena may be instrumental for the degenerative process. This dissociation between convulsive and neurodegenerative properties of kainic acid, however, does not argue against a role of an endogenous substance related to kainic acid in the etiology of temporal lobe seizure disorders.
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PMID:Intrahippocampal kainic acid, seizures and local neuronal degeneration: relationships assessed in unanesthetized rats. 717 85

The activity of acetylcholinesterase (AChE) and monoaminoxidase (MAO) in the field CA3 of rabbit's hippocampus was studied with histochemical methods during prolonged posttetanic potentiation (PTP), evoked by short (20 s) low-frequency (20/s) stimulation of n. septo-fimbrialis. Studies were conducted 20 min (group I) and 60 min (group II) after tetanization. In the group I a decrease in AChE activity was observed, especially in str. pyramidale and in the adjacent region of str. oriens. In the group II AChE activity increased, mostly in the external part of str. radiatum. MAO activity increased in both animal groups. For the group I a low (r = 0,42), but significant (P less than 0.05) correlation between PTP value and change in response to AChE was discovered. The reduction of activity 20 min after tetanization may be due to non-specific effect of tetanization as such and to a relatively short posttetanic depression. The increase in MAO activity is interpreted as an indirect confirmation of the part of the monoaminoergic systems in stabilization of plastic rearrangements elicited by tetanization.
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PMID:[Effect of prolonged post-tetanic potentiation on the activity of mediator metabolism enzymes in the hippocampus of rabbits]. 726 88

Levels of mRNA for c-fos, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), TrkB, and TrkC were studied using in situ hybridization in the rat brain at different reperfusion times after unilateral middle cerebral artery occlusion (MCAO). Short-term (15 min) MCAO, which does not cause neuronal death, induced elevated BDNF mRNA expression confined to ipsilateral frontal and cingulate cortices outside the ischemic area. With a longer duration of MCAO (2 h), which leads to cortical infarction, the increase was more marked and elevated BDNF mRNA levels were also detected bilaterally in dentate granule cells and CA1 and CA3 pyramidal neurons. Maximum expression was found after 2 h of reperfusion. At 24 h BDNF mRNA expression had returned to control values. In the ischemic core of the parietal cortex only scattered neurons were expressing high levels of BDNF mRNA after 15 min and 2 h of MCAO. Analysis of different BDNF transcripts showed that MCAO induced a marked increase of exon III mRNA but only small increases of exon I and II mRNAs in cortex and hippocampus. In contrast to BDNF mRNA, elevated expression of c-fos mRNA was observed in the entire ipsilateral cerebral cortex, including the ischemic core, after both 15 min and 2 h of MCAO. Two hours of MCAO also induced transient, bilateral increases of NGF and TrkB mRNA levels and a decrease of NT-3 mRNA expression, confined to dentate granule cells. The upregulation of BDNF mRNA expression in cortical neurons after MCAO is probably triggered by glutamate through a spreading depression-like mechanism. The lack of response of the BDNF gene in the ischemic core may be due to suppression of signal transduction or transcription factor synthesis caused by the ischemia. The observed pattern of gene expression after MCAO agrees well with a neuroprotective role of BDNF in cortical neurons. However, elevated levels of NGF and BDNF protein could also increase synaptic efficacy in the postischemic phase, which may promote epileptogenesis.
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PMID:Regulation of brain-derived neurotrophic factor gene expression after transient middle cerebral artery occlusion with and without brain damage. 758 36

The consequence of long-term potentiation (LTP) of hippocampal commissural inputs was investigated in an auditory gating paradigm. Auditory evoked potentials (AEPs) were recorded in the CA3b region of the hippocampus of rats anesthesitized with chloral hydrate. Two tones were delivered 0.5 sec apart; in this paradigm, the second AEP is diminished compared to the first. Electrical stimulation was applied to hippocampal commissural fibers to generate field potentials and population spikes which were recorded at the same site as the AEPs. LTP of the commissural input (initiated by three trains of 250 Hz/1 sec stimulation) was associated with changes in the AEPs: on average, the response to the first tone decreased and the response to the second tone increased, resulting in the disruption of auditory gating. When high-frequency stimulation of the commissural input failed to result in LTP, no effect on the AEPs was seen. If 3-(2-carboxypiperazin-4-yl)-propyl-L-phosphonic acid (CPP; 6 mg/kg, i.p.), an antagonist to the NMDA subclass of glutamate receptors, was administered prior to high-frequency stimulation, LTP induction was blocked and AEPs were not affected. Finally, reversal of LTP, achieved by high-frequency stimulation of CA3 input that was heterosynaptic to the particular commissural fibers at which the LTP was originally generated, caused disrupted auditory gating to return to normal. A model of reciprocal LTP and heterosynaptic depression of commissural and auditory input pathways is proposed to explain these findings.
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PMID:Long-term potentiation disrupts auditory gating in the rat hippocampus. 764 22

The hippocampus and related structures are thought to be capable of 1) representing cortical activity in a way that minimizes overlap of the representations assigned to different cortical patterns (pattern separation); and 2) modifying synaptic connections so that these representations can later be reinstated from partial or noisy versions of the cortical activity pattern that was present at the time of storage (pattern completion). We point out that there is a trade-off between pattern separation and completion and propose that the unique anatomical and physiological properties of the hippocampus might serve to minimize this trade-off. We use analytical methods to determine quantitative estimates of both separation and completion for specified parameterized models of the hippocampus. These estimates are then used to evaluate the role of various properties and of the hippocampus, such as the activity levels seen in different hippocampal regions, synaptic potentiation and depression, the multi-layer connectivity of the system, and the relatively focused and strong mossy fiber projections. This analysis is focused on the feedforward pathways from the entorhinal cortex (EC) to the dentate gyrus (DG) and region CA3. Among our results are the following: 1) Hebbian synaptic modification (LTP) facilitates completion but reduces separation, unless the strengths of synapses from inactive presynaptic units to active postsynaptic units are reduced (LTD). 2) Multiple layers, as in EC to DG to CA3, allow the compounding of pattern separation, but not pattern completion. 3) The variance of the input signal carried by the mossy fibers is important for separation, not the raw strength, which may explain why the mossy fiber inputs are few and relatively strong, rather than many and relatively weak like the other hippocampal pathways. 4) The EC projects to CA3 both directly and indirectly via the DG, which suggests that the two-stage pathway may dominate during pattern separation and the one-stage pathway may dominate during completion; methods the hippocampus may use to enhance this effect are discussed.
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PMID:Hippocampal conjunctive encoding, storage, and recall: avoiding a trade-off. 770 10

We investigated the effect of long-term potentiation (LTP) of the perforant path-granule cell synapse, on the synthesis of DNA in the target area and in polysynaptically stimulated hippocampal (CA3/CA1) and cortical areas (entorhinal, temporal, and occipital cortices) in the rat. The contralateral nonstimulated side was used as a control. The degree of LTP was indexed by the field EPSP and population spike amplitude recorded in the dentate area of the stimulated side before and after high frequency stimulation (250 Hz, 250 ms) every 30 min. DNA synthesis was evaluated in tissue homogenates after a 3-h period of incorporation of 3H-thymidine. DNA synthesis was significantly lower in the stimulated side in the hippocampal cortex CA3/CA1 (-25%), and in the entorhinal cortex (-50%), but not in the dentate area. In addition, the occurrence of preparations without expression of LTP allowed the analysis of unscheduled brain DNA synthesis (UBDS) in a supposedly long-term depression (LTD) subgroup. UBDS was higher in the group without LTP (no-LTP group) than in that with a significant LTP expression (LTP-group) on both sides of the brain. Furthermore, correlative analyses revealed that UBDS covaried with LTP of the EPSP (but not of population spike) in the dentate area and in extratarget hippocampal subregions on both sides and in dorsal cortex on the stimulated side. Further, regional crosscorrelation analyses revealed a high degree of coupling among brain sites following LTP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Unscheduled brain DNA synthesis, long-term potentiation, and depression at the perforant path-granule cell synapse in the rat. 771 92

The K+ channel activators diazoxide and cromakalim were investigated for effects on 4-aminopyridine (4AP)-induced epileptiform activity in adult rat hippocampal slices maintained in vitro. Under normal conditions of oxygenation, 4AP (50 microM) induced two types of field potentials in extracellular recordings from the CA3 stratum radiatum (apical dendritic region): epileptiform interictal discharge-like events occurring at a frequency of 0.75 +/- 0.36 Hz and long-lasting negative-going potentials mediated by GABA receptor activation that occurred at 0.03 +/- 0.01 Hz (n = 36 slices). Neither diazoxide (0.65-1.3 mM, n = 21 slices) nor cromakalim (50-200 microM, n = 6 slices) altered these two types of discharge. Brief periods of anoxia (4-6 min) reduced the frequency of the 4AP-induced interictal-like events (from 0.75 +/- 0.36 Hz to 0.19 +/- 0.15 Hz, n = 20 slices). In 45% of the experiments, the depressant effect of anoxia was preceded by a period of hyperexcitability consisting of a transient (36.1 +/- 12.9 sec) increase in the frequency of interictal-like events riding on a negative-going DC shift (n = 9 slices). Both responses to anoxia were reversible upon reoxygenation. In contrast, the rate of occurrence of the GABA-mediated potentials was unaffected by the anoxic episodes. Perfusion with cromakalim (n = 4 slices) or diazoxide (n = 5 slices) abolished the initial period of hyperexcitability produced by O2 deprivation but did not alter the subsequent depression of activity. Our experiments indicate that the K+ channel activators can prevent the initial hyperexcitability produced by anoxia, but do not influence 4AP-induced epileptiform activity in normoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potassium channel activators counteract anoxic hyperexcitability but not 4-aminopyridine-induced epileptiform activity in the rat hippocampal slice. 776 Sep 73

Male rats housed in mixed-sex groups quickly established dominance hierarchies in which subordinates appeared severely stressed. Subordinate rats had elevated basal corticosterone (CORT) levels relative to dominants and individually housed controls. Several subordinates had blunted CORT responses to a novel stressor, leading to the classification of subordinates as either stress-responsive or nonresponsive. Binding to 5-HT1A receptors was reduced in stress-responsive subordinates compared to controls throughout hippocampus and dentate gyrus. Decreased binding was observed in nonresponsive subordinates only in CA3 of hippocampus. In addition, 5-HT1A binding was decreased in CA1, CA3, and CA4 in dominants compared to controls. Binding to 5-HT2 receptors was increased in parietal cortex in both responsive and nonresponsive subordinates compared to controls. No changes were observed in binding to 5-HT1B receptors. These results are discussed in the context of regulation of the serotonergic system by stress and glucocorticoids and possible relevance to the pathophysiology of depression.
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PMID:Serotonin receptor binding in a colony model of chronic social stress. 777 47


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