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

Neocortical slices from young [postnatal day (P) 5-8], juvenile (P14-18), and adult (>P28) rats were exposed to long periods of hypoxia. Field potential (FP) responses to orthodromic synaptic stimulation, the extracellular DC potential, and the extracellular Ca2+ concentration ([Ca2+]o] were measured simultaneously in layers II/III of primary somatosensory cortex. Hypoxia caused a 42 and 55% decrease in the FP response in juvenile and adult cortex, respectively. FP responses recorded in slices from young animals were significantly more resistant to oxygen deprivation as compared with the juvenile (P < 0.01) and adult age group (P < 0.001) and declined by only 3% in amplitude. In adult cortex, hypoxia elicited, after 7 +/- 4.5 min (mean +/- SD), a sudden anoxic depolarization (AD) with an amplitude of 14 +/- 6 mV and a duration of 0.89 +/- 0.28 min at half-maximal amplitude. Although the AD onset latency was significantly longer in P5-8 (12.5 +/- 4.9 min, P < 0.001) and P14-18 (8.7 +/- 3.2 min, P < 0.002) cortex, the amplitude and duration of the AD was larger in young (45.7 +/- 7.6 mV, 2.19 +/- 0.71 min, both P < 0.001) and juvenile animals (29.9 +/- 9.1 mV, P < 0.001, 0.96 +/- 0.26 min, P > 0.05) when compared with the adults. The hypoxia-induced [Ca2+]o decrease was significantly (P < 0.002) larger in young cortex (1,115 +/- 50 microM) as compared with the adult (926 +/- 107 microM). Prolongation of hypoxia after AD onset for >5 min elicited in young and juvenile cortex a long-lasting AD with an amplitude of 40.5 mV associated with a decrease in [Ca2+]o by >1 mM. On reoxygenation, only slices from these age groups showed spontaneous repetitive spreading depression in 3 out of 26 cases. In adults, the same protocol caused a significantly (P < 0.05) smaller and shorter AD and never a spreading depression. However, recovery in synaptic transmission after this long-term hypoxia was better in young and juvenile cortex, indicating a prolonged or even irreversible deficiency in synaptic function in mature animals. Application of ketamine caused a 49% reduction in the initial amplitude of the AD in juvenile cortex but did not significantly affect the AD in slices from adult animals. These data indicate that the young and juvenile cortex tolerates much longer periods of oxygen deprivation as compared with the adult, but that a sufficiently long hypoxia causes severe pathophysiological activity in the immature cortex. This enhanced sensitivity of the immature cortex is at least partially mediated by activation of N-methyl-D-aspartate receptors.
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PMID:Hypoxia-induced dysfunction in developing rat neocortex. 931 Apr 13

Modulation of hippocampal CA3-CA1 synaptic transmission during metabotropic glutamate receptor (mGluR) activation was investigated in juvenile (postnatal day (P) 15-21) and young adult rats (P28-35). The mGluR agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (ACPD) depressed the EPSP slope more in young adults than juveniles. ACPD increased paired-pulse facilitation (PPF) at both ages. The group I mGluR antagonist (+)-alpha-methylcarboxyphenylglycine (MCPG) inhibited the ACPD-mediated depression of the EPSP slope and completely blocked the increase in PPF only in young adults. Minimal effects of MCPG on ACPD-dependent synaptic depression were observed in juveniles. These data suggest that presynaptic group I mGluR-mediated synaptic inhibition increases across late postnatal development. In addition, other mGluR subtypes, with the ability to depress presynaptic function, appear to be present in juveniles.
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PMID:Development of metabotropic glutamate receptor-mediated synaptic inhibition. 937 31

Depression of excitatory postsynaptic potentials (EPSPs) by the GABA(b) agonist, baclofen, was compared in hippocampal slices from juvenile (postnatal day (P) 15-21) and young adult (P28-35) rats. EPSP inhibition following baclofen application was not different between age groups, however, paired-pulse facilitation (PPF) increased more in young adults relative to juveniles. The differential effect of baclofen on PPF was not due to tonic receptor activity, since the GABA(b) antagonist, saclofen, did not differentially modify PPF. The baclofen-mediated increase in PPF for juvenile slices could be enhanced by first increasing transmitter release through an increased bath Ca2+ concentration. These findings suggests that ligand-mediated presynaptic depression is inversely related to the level of transmitter release and maturation of presynaptic inhibition is related to development of release.
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PMID:GABA(b) receptors differentially regulate hippocampal CA1 excitatory synaptic transmission across postnatal development in the rat. 965 62

Amplitudes of EPSPs evoked by repetitive presynaptic action potentials can either decrease (synaptic depression) or increase (synaptic facilitation). To determine whether facilitation and depression in the connections between neocortical pyramidal cells varied with the identity of the pre- or the postsynaptic cell and whether they changed during postnatal development, whole-cell voltage recordings were made simultaneously from two or three pyramidal cells in layers 2/3 and 5 of the rat sensorimotor cortex. Unitary EPSPs were evoked when pre- and postsynaptic neurons were in the same and in different layers. In young [postnatal day 14 (P14)] cortex, EPSPs evoked in all connected neurons depressed. The degree of depression was layer specific and was determined by the identity of the presynaptic cell. EPSPs evoked by stimulation of presynaptic layer 5 neurons depressed significantly more than did those evoked by stimulation of layer 2/3 neurons. In mature cortex (P28), however, the EPSPs evoked in these connected neurons facilitated to a comparable degree regardless of the layer in which pre- and postsynaptic neurons were located. The results suggest that in young cortex the degree of synaptic depression in connected pyramidal cells is determined primarily by whether the presynaptic cell was in layer 2/3 or 5 and that maturation of the cortex involves a developmental switch from depression to facilitation between P14 and P28 that eliminates the layer-specific differences. A functional consequence of this switch is that in mature cortex the spread of excitation between neocortical pyramidal neurons is enhanced when action potentials occur in bursts.
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PMID:Developmental switch in the short-term modification of unitary EPSPs evoked in layer 2/3 and layer 5 pyramidal neurons of rat neocortex. 1023 15

Plasticity was induced in the barrel cortex of adolescent rats by depriving every second vibrissa on the contralateral vibrissa pad. This produced a chessboard pattern of barrels in the cortex where each barrel receiving its principal input from a spared vibrissa was surrounded by barrels for which the principal vibrissa had been deprived and conversely, each barrel receiving its principal input from a deprived vibrissa was surrounded by barrels for which the principal vibrissa had been spared. After 7 days' deprivation, responses to the regrown vibrissae were depressed in layers II/III (49% of control levels) and IV (60%). Depression was far greater than that seen with "all vibrissa" deprivation, suggesting that activity in the spared vibrissae accentuated the depression of the deprived vibrissae. Depression was not due to subcortical changes as thalamic Ventral Posterior Medial (VPM) responses to deprived vibrissa were unchanged. The short latency responses in layer IV (5-7 ms) were unaffected by deprivation, but the number of cells responding at intermediate latencies (8-13 ms) was markedly reduced (to 66% of control). Potentiation of the spared vibrissa response was substantial in the near side of the neighbouring barrel (2.2-fold increase in layers II/III, 2.9-fold in layer IV) but had not spread to the far side after 7 days' deprivation. Sparing multiple vibrissae may increase the rate of potentiation since 7 days is insufficient time for potentiation in single vibrissa spared animals. Potentiation was not due to subcortical changes as thalamic VPm responses to the spared vibrissa were normal. However, in the spared barrel the response latency decreased by 1-2 ms. Only the cells responding at short latency exhibited potentiated responses (39% increase) suggesting that some thalamocortical plasticity is still possible at P28-35. These results show that chessboard pattern deprivation is capable of inducing substantial plasticity over a wide area of barrel cortex. All the major forms of plasticity seen with other vibrissa deprivation patterns were present, although no other single deprivation pattern studied so far causes the complete repertoire seen with chessboard deprivation.
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PMID:The effect of vibrissa deprivation pattern on the form of plasticity induced in rat barrel cortex. 1044 61

Previous studies have demonstrated that, compared to adults, postnatal day 17 (P17) and P28 rats show remarkable cognitive recovery in the Morris water maze (MWM) following fluid percussion injury (FPI). This observed age-at-trauma effect could result from either younger animals solving the MWM task using noninjured neural circuitry or an inability of adult and P28 brains to activate appropriate neural networks due to trauma-induced neurological dysfunction. To address these possibilities, we compared "activated" brain regions during normal MWM acquisition and following FP injury. To generate "activated" images of the brain while animals were performing the MWM task, qualitative [14C]2-deoxy-D-glucose was conducted on days 2, 5, and 14 during training in sham and injured adult, P28, and P17 rats. When maturational changes in cerebral glucose metabolism are taken into account, the results suggests similar activity changes in the cerebral cortex and lacunosum moleculare of CA1 during acquisition in all age groups, suggesting that the developmental rates of MWM learning do not correspond to different patterns of activated cerebral metabolism. Injured P17s, showing no latency deficits, revealed activated cerebral metabolic patterns similar to noninjured P17 animals. In P28 and adult cases, animals exhibited cognitive deficits and their metabolic studies indicated that the cortical-hippocampal pattern of activation was disrupted by marked injury-induced metabolic depression, which primarily affected the ipsilateral hemisphere and lasted for as long as 14 days in adult animals.
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PMID:Mapping cerebral glucose metabolism during spatial learning: interactions of development and traumatic brain injury. 1120 Feb 48

Refinement of the retinal pathways to the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN) is mediated by nitric oxide (NO). Long-term depression (LTD) can also be induced in SC and LGN during the time at which these pathways are refined, and this LTD is partially dependent on NO and L-type Ca(2+) channel function. In an effort to determine whether NO-mediated pathway refinement is also mediated by Ca(2+) channel function, we have examined the refinement of the retinocollicular and retinogeniculate pathways in mice which lack the gene for the Ca(2+) channel beta(3) subunit (CCKO) and which have significantly reduced L-type Ca(2+) currents. Injections of the anterograde tracer cholera toxin subunit B/HRP were made into one eye of these knockout animals and in wild-type mice ages postnatal day (P) 13, P19, and P26. After 48 hours, mice were perfused and sections processed by using tetramethylbenzidine histochemistry. Labeling distribution in some animals was analyzed quantitatively. Obvious differences in the distribution of the ipsilateral retinocollicular pathway were observed at P15, with the pathway being more exuberant in CCKO mice. This difference was statistically significant. More subtle differences were seen at P21 and P28. Obvious differences were also seen in the contralateral retinogeniculate pathway which in CCKO mice filled most of the domain normally occupied by ipsilateral eye fibers. This difference was also statistically significant. We conclude that reduction in L-type Ca(2+) currents has an effect on axonal refinement similar to that which occurs in NO knockout mice, which supports the possibility that L-type Ca(2+) channel-dependent LTD mediates NO-dependent axonal refinement.
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PMID:Development of the visual pathway is disrupted in mice with a targeted disruption of the calcium channel beta(3)-subunit gene. 1174 16

The central nervous system (CNS) exhibits remarkable plasticity in early life and can be altered significantly by various prenatal influences. We previously showed that prenatal exposure to morphine altered kinetic properties of N-methyl-D-aspartate (NMDA) receptor-mediated synaptic currents in the hippocampus of young rat offspring at the age of 14 days (P14). The present study further investigates whether NMDA receptor-mediated synaptic plasticity and/or cyclic adenosine monophosphate-responsive element-binding protein (CREBSerine-133), an important transcription factor underlying learning and memory, can be altered by prenatal morphine exposure in these offspring. Subsequently, the Morris water maze task was performed at the older ages (P28-P31). The magnitude of long-term depression (LTD) generated by a low-frequency stimulation (LFS, 1 Hz for 15 min) in hippocampal slices from the vehicle-control offspring (P14) was significantly larger than that in slices from the morphine-treated offspring, although there was no such difference in the magnitude of long-term potentiation (LTP) elicited by a high-frequency stimulation (100 Hz for 1 s) between the two groups. Comparison of the expression range of glutamatergic synaptic plasticity in slices from the vehicle-control and morphine-treated offspring, calculated as the difference in the maximal magnitude between LTP and LTD, demonstrated a remarkably smaller range in the slices from the morphine-treated offspring. In addition, the decreased phosphorylation of CREBSerine-133 and the impaired ability of spatial learning were also seen in the morphine-treated offspring, as compared with the vehicle-control offspring. Collectively, the study suggests that maternal exposure to morphine reduces the range of synaptic plasticity by decreasing the expression of LTD, but not of LTP, in CA1 pyramidal neurons of the hippocampus from rat offspring. More importantly, decreased phosphorylation of CREBSerine-133 may play a role for the impaired spatial learning and memory in rat offspring exposure to prenatal morphine. Thus, the findings here may provide important insights into cellular/molecular mechanisms underlying pathophysiological changes in the CNS of young offspring from morphine-addicted mothers and serve as a basis for possible therapeutic intervention.
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PMID:Prenatal administration of morphine decreases CREBSerine-133 phosphorylation and synaptic plasticity range mediated by glutamatergic transmission in the hippocampal CA1 area of cognitive-deficient rat offspring. 1475 Jun 54

Schaffer collateral excitatory synapses onto CA1 pyramidal cells are subject to significant modulation by short-term plasticity. This presynaptic, history-dependent modulation of neurotransmitter release causes synaptic transmission to be sensitive to the frequency of the input. As a result, temporally irregular input patterns, such as those observed in vivo, produce synaptic responses over a very wide dynamic range that reflect a balance of short-term facilitation and short-term depression. The neonatal period is an important developmental period in the hippocampus, when functional representations of an animal's environment are being established through exploratory behavior. The strength of excitatory synapses and their modulation by short-term plasticity are critical to this process. One form of short-term plasticity, paired-pulse facilitation, has been shown to decrease as juvenile rats mature into young adults. However, little is known about the neonatal modulation of other forms of short-term plasticity, including the responses to temporally complex stimuli. We examined developmental modulation of the short-term dynamics of Schaffer collateral excitatory synapses onto CA1 pyramidal cells in acute hippocampal slices, using both constant frequency stimuli and natural stimulus patterns that were taken from in vivo recording of spike patterns of hippocampal cells. In response to constant frequency stimulation, synapses in slices from young adult rats (P28-P35) showed less short-term depression than did those in slices from juveniles (P12-P18). However, when the natural stimulus pattern (containing a wide mix of frequencies) was used, synapses from young adults instead showed more short-term depression and less short-term facilitation than did juveniles. Comparing the natural stimulus pattern responses with constant frequency stimulation of a similar frequency, we found that the average responses were similar in young adults (both showed modest depression). However, in juveniles, the natural pattern produced robust facilitation while constant frequency stimulation caused a large short-term depression. Our results reveal that there are developmental changes both in individual forms of short-term plasticity and in the relative balance between short-term facilitation and short-term depression that will alter the signal transfer characteristics of these synapses.
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PMID:Responses of excitatory hippocampal synapses to natural stimulus patterns reveal a decrease in short-term facilitation and increase in short-term depression during postnatal development. 1626 53

Infants passively exposed to morphine or heroin through their addicted mothers usually develop characteristic withdrawal syndrome of morphine after birth. In such early life, the central nervous system exhibits significant plasticity and can be altered by various prenatal influences, including prenatal morphine exposure. Here we studied the effects of prenatal morphine exposure on postsynaptic density protein 95 (PSD-95), an important cytoskeletal specialization involved in the anchoring of the NMDAR and neuronal nitric oxide synthase (nNOS), of the hippocampal CA1 subregion from young offspring at postnatal day 14 (P14). We also evaluated the therapeutic efficacy of dextromethorphan, a widely used antitussive drug with noncompetitive antagonistic effects on NMDARs, for such offspring. The results revealed that prenatal morphine exposure caused a maximal decrease in PSD-95 expression at P14 followed by an age-dependent improvement. In addition, prenatal morphine exposure reduced not only the expression of nNOS and the phosphorylation of cAMP responsive element-binding protein at serine 133 (CREB(Serine-133)), but also the magnitude of long-term depression (LTD) at P14. Subsequently, the morphine-treated offspring exhibited impaired performance in long-term learning and memory at later ages (P28-29). Prenatal coadministration of dextromethorphan with morphine during pregnancy and throughout lactation could significantly attenuate the adverse effects as described above. Collectively, the study demonstrates that maternal exposure to morphine decreases the magnitude of PSD-95, nNOS, the phosphorylation of CREB(Serine-133), and LTD expression in hippocampal CA1 subregion of young offspring (e.g., P14). Such alterations within the developing brain may play a role for subsequent neurological impairments (e.g., impaired performance of long-term learning and memory). The results raise a possibility that postsynaptic density proteins could serve an important role, at least in part, for the neurobiological pathogenesis in offspring from the morphine-addicted mother and provide tentative therapeutic strategy.
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PMID:Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine-addicted mother: Beneficial effect of dextromethorphan. 1659 5


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