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

Extinction of escape behavior in the water maze due to the removal of the platform, was hypothesized to induce a negative state, including the development of immobility, which is held to reflect a state of "despair" when measured in the forced swimming test. 27 aged and 8 adult animals (26 and 3 months old Wistar rats, respectively) were tested in the water maze during nine days with a platform hidden, followed by 7 days of extinction trials with the platform absent. As expected, both age groups developed immobility over the extinction trials, with the aged showing more than the adults. To examine whether the age difference in immobility was related to performance differences during acquisition, the aged were subdivided into superior, intermediate and inferior learners (n = 9 per group) on the basis of overall times to platform during acquisition, and compared with each other and the adults. Results showed that the aged inferior learners displayed the highest levels of immobility among the aged. Immobility scores were then correlated with post-mortem neurotransmitter contents in the hippocampus and ventral striatum. In the ventral striatum, levels of immobility were correlated with levels of acetylcholine, dopamine and the metabolite dihydroxyphenylacetic acid in the aged, and with norepinephrine in the adults. The data support the hypothesis that multiple extinction trials in the water maze result in immobility that may indicate "behavioral despair," and that striatal neurotransmitter systems correlate with the degree of its expression. The concept of extinction-induced despair is held to provide the promise of a conceptual and empirical model of human depression that is the consequence of loss of reinforcers.
Neurobiol Learn Mem 2004 Sep
PMID:Extinction-induced immobility in the water maze and its neurochemical concomitants in aged and adult rats: a possible model for depression? 1534 98

Cocaine produces multiple neuroadaptations with chronic repeated use. Many of these neuroadaptations can be reversed or normalized by extinction training during withdrawal from chronic cocaine self-administration in rats. This article reviews our past and present studies on extinction-induced modulation of the neuroadaptive response to chronic cocaine in the mesolimbic dopamine system, and the role of this modulation in addictive behavior in rats. Extinction training normalizes tyrosine hydroxylase levels in the nucleus accumbens (NAc) shell, an effect that could help ameliorate dysphoria and depression associated with withdrawal from chronic cocaine use. Extinction training also increases levels of GluR1 and GluR2/3 AMPA receptor subunits, while normalizing deficits in NR1 NMDA receptor subunits, in a manner consistent with long-term potentiation of excitatory synapses in the NAc shell. Our results suggest that extinction-induced increases in AMPA and NMDA receptors may restore deficits in cortico-accumbal neurotransmission in the NAc shell and facilitate inhibitory control over cocaine-seeking behavior. Other changes identified by gene expression profiling, including up-regulation in the AMPA receptor aggregating protein Narp, suggest that extinction training induces extensive synaptic reorganization. These studies highlight potential benefits for extinction training procedures in the treatment of drug addiction.
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PMID:Extinction training regulates neuroadaptive responses to withdrawal from chronic cocaine self-administration. 1546 21

We have recently proposed that the maintenance of hippocampal long-term potentiation (LTP) and depression depends on at least two required processes: induction of LTP must set (1) process-specific 'synaptic tags' which capture (2) process-unspecific plasticity-related proteins (PRPs), synthesized via a heterosynaptic interaction [Neurobiol Learn Mem 82 (2004) 12]. The 'tag' as well as the PRPs are characterized by a relatively short half-life of several minutes up to a few hours before they degrade most likely by processes such as dephosphorylation. The question now arose whether the 'tags' can also be reset in an activity-dependent manner, thus preventing the processing of PRPs with the result of transient short-lasting plasticity. Here we have investigated this topic during early-LTP and found that low-frequency stimulation shortly after early-LTP-induction (5 min) resets the 'tag' or the 'tag complex' of macromolecules preventing any lasting forms of LTP and thus, preventing the formation of a memory trace.
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PMID:Resetting of 'synaptic tags' is time- and activity-dependent in rat hippocampal CA1 in vitro. 1550 7

Global left ventricular (LV) systolic dysfunction is the strongest predictor of morbidity and mortality in Chagas disease. Echocardiography is considered the gold standard for the detection of LV dysfunction, but not always available in endemic areas where chagasic cardiomyopathy is most common. Brain natriuretic peptide (BNP) is a neurohormone that has been recently described as a simple and inexpensive diagnostic and prognostic marker for patients with congestive heart failure. Chagasic patients (n = 63) and non-infected healthy individuals (n = 18) were recruited prospectively and underwent complete clinical examination, echocardiography and 24-h Holter monitoring. BNP was measured from thawed plasma samples using the Triage BNP test. We observed high levels of BNP in association with depression of LV ejection fraction, with increase of LV end-diastolic diameter and with LV premature complexes. An elevated concentration of BNP, defined as a concentration of 60 pg/ml or more, had a sensitivity of 91.7%, specificity of 82.8%, positive predictive value of 52.4%, and negative predictive value of 98% for detecting LV dysfunction (LV ejection fraction < 40%).BNP measurement using a simple, relatively inexpensive and rapid test has a promising role in identifying LV dysfunction associated with chagasic cardiomyopathy. Equally important, patients with Trypanosoma cruzi infection who have low levels of BNP level in plasma have a very low likelihood of severe cardiac involvement, and echocardiography is probably not necessary.
Mem Inst Oswaldo Cruz 2004 Oct
PMID:Brain natriuretic peptide and left ventricular dysfunction in chagasic cardiomyopathy. 1555 79

Endogenous cyclical changes in the levels of estrogen can have marked effects on hippocampal synaptic plasticity. In two experiments, we examined the effect of chronic estrogen loss and replacement following ovariectomy on the induction of bidirectional changes in synaptic plasticity in the CA1 region in vivo. In Experiment 1, ovariectomy carried out either 5 days or 5 weeks before testing impaired the induction of long-term depression (LTD) and but not long-term potentiation (LTP). In Experiment 2, chronic estrogen replacement (0.2 ml of 10 microg injection of 17beta-estradiol every 48 h) over the course of 5 weeks enhanced the magnitude of paired-pulse-induced LTD in the CA1 region but had no effect on the induction of LTP. The results demonstrate that acute and chronic estrogen deprivation disrupted dynamic synaptic plasticity processes in the hippocampal CA1 region and that this disruption was ameliorated by chronic estrogen replacement. The findings are discussed with reference to: (1) the contribution of Ca(2+) regulated synaptic signalling pathways in the CA1 region to estradiol modulation of LTP and LTD and (2) the potential functional significance of ovariectomy-induced changes in synaptic plasticity for learning and memory processes.
Neurobiol Learn Mem 2005 Jan
PMID:Ovariectomy-induced disruption of long-term synaptic depression in the hippocampal CA1 region in vivo is attenuated with chronic estrogen replacement. 1560 84

Many studies of the neural mechanisms of learning have focused on habituation, a simple form of learning in which a response decrements with repeated stimulation. In the siphon-elicited siphon withdrawal reflex (S-SWR) of the marine mollusk Aplysia, the prevailing view is that homosynaptic depression of primary sensory afferents underlies short-term habituation. Here we examined whether this mechanism is also utilized in habituation of the tail-elicited siphon withdrawal reflex (T-SWR), which is triggered by an independent, polysynaptic afferent pathway that converges onto the same siphon motor neurons (MNs). By using semi-intact preparations in which tail and/or siphon input to siphon MNs could be measured, we found that repeated tail stimuli administered in the presence of a reversible conduction block of the nerves downstream of the tail sensory neurons (SNs) completely abolished the induction of habituation. Subsequent retraining revealed no evidence of savings, indicating that the tail SNs and their immediate interneuronal targets are not the locus of plasticity underlying T-SWR habituation. The networks closely associated with the siphon MNs are modulated by cholinergic inhibition. We next examined the effects of network disinhibition on S-SWR and T-SWR habituation using an Ach receptor antagonist d-tubocurarine. We found that the resulting network disinhibition disrupted T-SWR, but not S-SWR, habituation. Indeed, repeated tail stimulation in the presence of d-tubocurarine resulted in an initial enhancement in responding. Lastly, we tested whether habituation of T-SWR generalized to S-SWR and found that it did not. Collectively, these data indicate that (1) unlike S-SWR, habituation of T-SWR does not involve homosynaptic depression of SNs; and (2) the sensitivity of T-SWR habituation to network disinhibition is consistent with an interneuronal plasticity mechanism that is unique to the T-SWR circuit, since it does not alter S-SWR.
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PMID:Differential role of inhibition in habituation of two independent afferent pathways to a common motor output. 1564 95

In many regions of the brain, including the mammalian cortex, the strength of synaptic transmission can be bidirectionally regulated by cortical activity (synaptic plasticity). One line of evidence indicates that long-term synaptic potentiation (LTP) and long-term synaptic depression (LTD), correlate with the phosphorylation/dephosphorylation of sites on the alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit protein GluR1. Bidirectional synaptic plasticity can be induced by different frequencies of presynaptic stimulation, but there is considerable evidence indicating that the key variable is calcium influx through postsynaptic N-methyl-d-aspartate (NMDA) receptors. Here, we present a biophysical model of bidirectional synaptic plasticity based on [Ca2+]-dependent phospho/dephosphorylation of the GluR1 subunit of the AMPA receptor. The primary assumption of the model, for which there is wide experimental support, is that the postsynaptic calcium concentration, and consequent activation of calcium-dependent protein kinases and phosphatases, is the trigger for phosphorylation/dephosphorylation at GluR1 and consequent induction of LTP/LTD. We explore several different mathematical approaches, all of them based on mass-action assumptions. First, we use a first order approach, in which transition rates are functions of an activator, in this case calcium. Second, we adopt the Michaelis-Menten approach with different assumptions about the signal transduction cascades, ranging from abstract to more detailed and biologically plausible models. Despite the different assumptions made in each model, in each case, LTD is induced by a moderate increase in postsynaptic calcium and LTP is induced by high Ca2+ concentration.
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PMID:A model of bidirectional synaptic plasticity: from signaling network to channel conductance. 1602 75

In a series of three experiments, increasing working memory (WM) load was demonstrated to reduce the executive control of attention, measured via task-switching and inhibitory control paradigms. Uniquely, our paradigms allowed comparison of the ability to exert executive control when the stimulus was either part of the currently rehearsed memory set or an unrelated distractor item. The results demonstrated a content-specific effect-insofar as switching attention away from, or exerting inhibitory control over, items currently held in WM was especially difficult-compounded by increasing WM load. This finding supports the attentional control theory that active maintenance of competing task goals is critical to executive function and WM capacity; however, it also suggests that the increased salience provided to the contents of WM through active rehearsal exerts a content-specific influence on attentional control. These findings are discussed in relation to cue-induced ruminations, where active rehearsal of evocative information (e.g., negative thoughts in depression or drug-related thoughts in addiction) in WM typically results from environmental cuing. The present study has demonstrated that when information currently maintained in WM is reencountered, it is harder to exert executive control over it. The difficulty with suppressing the processing of these stimuli presumably reinforces the maintenance of these items in WM, due to the greater level of attention they are afforded, and may help to explain how the cue-induced craving/rumination cycle is perpetuated.
Mem Cognit 2005 Mar
PMID:Working memory and executive function: the influence of content and load on the control of attention. 1602 77

Aplysia motoneurons cocultured with a presynaptic sensory neuron exhibit homosynaptic depression when stimulated at low frequencies. A single bath application of serotonin (5HT) leads within seconds to facilitation of the depressed synapse. The facilitation is attributed to mobilization of neurotransmitter-containing vesicles from a feeding vesicle store to the depleted, readily releasable pool by protein kinase C (PKC). Here, we demonstrate that the calpain inhibitors, calpeptin, MG132, and ALLN, but not the proteasome inhibitors, lactacystin and clasto-lactacystin beta-lactone, block 5HT-induced facilitation of depressed synapses. Likewise the 5HT-induced enhancement of spontaneous miniature potentials (mEPSPs) frequency of depressed synapses is significantly reduced by calpeptin. In contrast, neither the facilitation of nondepressed synapses nor the enhancement of their mEPSPs frequency is affected by the inhibitor. The data suggest that action potentials-induced calcium influx activate calpains. These, in turn, play a role in the refilling processes of the depleted, releasable vesicle store.
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PMID:Calcium-activated proteases are critical for refilling depleted vesicle stores in cultured sensory-motor synapses of Aplysia. 1607 20

Temporal lobe epilepsy (TLE) is often accompanied by interictal behavioral abnormalities, such as fear and memory impairment. To identify possible underlying substrates, we analyzed long-term synaptic plasticity in two relevant brain regions, the lateral amygdala (LA) and the CA1 region of the hippocampus, in the kindling model of epilepsy. Wistar rats were kindled through daily administration of brief electrical stimulations to the left basolateral nucleus of the amygdala. Field potential recordings were performed in slices obtained from kindled rats 48 h after the last induced seizure, and in slices from sham-implanted and nonimplanted controls. Kindling resulted in a significant impairment of long-term potentiation (LTP) in both the LA and the CA1, the magnitude of which was dependent on the number of prior stage V seizures. Saturation of CA1-LTP, assessed through repeated spaced delivery of high-frequency stimulation, occurred at lower levels in kindled compared to sham-implanted animals, consistent with the hypothesis of reduced capacity of further synaptic strengthening. Furthermore, theta pulse stimulation elicited long-term depression in the amygdala in nonimplanted and sham-implanted controls, whereas the same stimulation protocol stimulation caused LTP in kindled rats. In conclusion, kindling differentially affects the magnitude, saturation, and polarity of LTP in the CA1 and LA, respectively, most likely indicating an activity-dependent mechanism in the context of synaptic metaplasticity.
Learn Mem
PMID:Kindling-induced changes in plasticity of the rat amygdala and hippocampus. 1620 4


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