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

1. The postnatal maturation of gamma-aminobutyric acid (GABA)B receptor-mediated presynaptic inhibition was studied in brain slices of rat somatosensory cortex maintained in vitro. Patchclamp techniques were used to record whole-cell inhibitory post-synaptic currents from layer II-III neurons in animals from postnatal days (P) 7-24. Monosynaptic inhibitory postsynaptic currents (IPSCs) were evoked after N-methyl-D-aspartate (NMDA) and non-NMDA type glutamate receptors had been blocked by D-amino-phosphonovaleric acid (D-AP5, 20 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM), respectively. These IPSCs were solely mediated by postsynaptic GABAA receptors because they were abolished by bicuculline (10 microM), reversed polarity near the chloride equilibrium potential, and were recorded with electrodes that contained Cs+ to block postsynaptic GABAB responses. 2. When pairs of stimuli separated by intervals of 0.1-10 s were used to evoke IPSCs, the second response was depressed, an effect that was maximal at 300 ms. Evoked IPSCs were also depressed by baclofen (10 microM). The paired pulse depression (PPD) of monosynaptic IPSCs was decreased or eliminated by 2-OH-saclofen (200 microM). These findings indicate that PPD of monosynaptic IPSCs was due to presynaptic GABAB receptor-mediated inhibition of GABA release. 3. There were no significant differences in the amounts of PPD in neurons from different age groups (P7-10, P12-17, P22-24) at any interstimulus interval tested (0.1-10 s).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential ontogenesis of presynaptic and postsynaptic GABAB inhibition in rat somatosensory cortex. 839 87

High-frequency activation of excitatory striatal synapses produces lasting changes in synaptic efficacy that may contribute to motor and cognitive functions. While some of the mechanisms responsible for the induction of long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic responses at striatal synapses have been characterized, much less is known about the factors that govern the direction of synaptic plasticity in this brain region. Here we report heterogeneous activity-dependent changes in the direction of synaptic strength in subregions of the developing rat striatum. Neurons in the dorsolateral region of the anterior striatum tended to express LTD after high-frequency afferent stimulation (HFS) in slices from animals aged P15-P34. However, HFS in dorsolateral striatum from P12-P14 elicited an N-methyl-D-aspartate (NMDA) receptor-dependent form of LTP. Synapses in the dorsomedial anterior striatum exhibited a propensity to express an NMDA-receptor dependent form of LTP across the entire developmental time period examined. The NMDA receptor antagonist (+/-)-2-amino-5-phosphopentanoic acid (APV) inhibited evoked excitatory postsynaptic potentials recorded in striatum obtained from P12-P15 rats but had little effect in striatum from older animals. The expression of multiple forms of synaptic plasticity in the striatum suggests mechanisms by which this brain region plays pivotal roles in the acquisition or encoding of some forms of motor sequencing and stereotypical behaviors.
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PMID:Regional and postnatal heterogeneity of activity-dependent long-term changes in synaptic efficacy in the dorsal striatum. 1098 15

Fast, precise, and sustained synaptic transmission at high frequency is thought to be crucial for the task of sound localization in the auditory brainstem. However, recordings from the calyx of Held synapse have revealed severe frequency-dependent synaptic depression, which tends to degrade the exact timing of postsynaptic spikes. Here we investigate the functional changes occurring throughout the critical period of synapse refinement from immature calyx terminal [postnatal day 5 (P5)] to after the onset of hearing (P12-P14). Surprisingly, for recordings near physiological temperature (35 degrees C), we find that P14 synapses are already able to follow extremely high input rates of up to 800 Hz. This ability stems in part from a remarkable shortening of presynaptic action potentials, which may lead to a lowering of release probability and decrease in synaptic delays during development. In addition, AMPA receptor-mediated EPSCs as well as quantal synaptic currents acquired progressively faster kinetics, although their mean amplitudes did not change significantly. NMDA receptor-mediated EPSCs, however, diminished with age, as indicated by a 50% reduction in mean amplitude and faster decay kinetics. Finally, the degree of synaptic depression was greatly attenuated with age, presumably because of a 2.5-fold or larger increase in the releasable pool of vesicles, which together with a decreasing release probability produces a fairly constant EPSC amplitude. This finely tuned orchestra of developmental changes thus simultaneously promotes speed while preventing premature vesicle pool depletion during prolonged bouts of firing. A few critical days in postnatal development can thus have a large impact on synaptic function.
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PMID:Fine-tuning an auditory synapse for speed and fidelity: developmental changes in presynaptic waveform, EPSC kinetics, and synaptic plasticity. 1112 94

The immature brain is much more sensitive to abnormal experience, particularly sleep deprivation, drug exposure, and maternal separation. The critical time period during which features in the brain's susceptibility to such experience change, however, has not yet been determined. In previous studies on rats, we found that neonatal treatment with clomipramine (CLI) during postnatal days 8--21 (P8-21) produced behavioral and physiological abnormalities in adult rats that resembled the abnormalities found in human endogenous depression. The objective of the present study is to determine (1) the critical (more specifically, the latest) time frame in which CLI treatment will produce adult depression and (2) the shortest treatment window during which CLI can induce adult depression. Male rats were neonatally treated with CLI (20 mg/kg, sc) twice daily or with an equivolume of saline. The treatment windows were P12--17, P14--20, P16--22, and P12--15. Six variables, including number of mounts, intromission, ejaculation, mount latency, ejaculation latency, and post-ejaculation interval, were measured visually between the ages of 4 and 5 months. Rats treated with CLI showed significant sexual impairment in treatment windows P12--17 and P14--20 and slight sexual deficiency in the short window P12--15. No significant sexual impairment was found in window P16--22. We concluded that P14--20 was the latest window during which CLI treatment produces adult sexual deficiency and that 6 days might be the shortest treatment window to produce significant behavior abnormalities.
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PMID:The critical window of brain development from susceptive to insusceptive. Effects of clomipramine neonatal treatment on sexual behavior. 1145 17

We examined age-dependent changes in short-term synaptic depression of monosynaptic excitatory postsynaptic potentials (EPSPs) recorded in lumbar motoneurons in hemisected spinal cords of neonatal Swiss-Webster mice between postnatal day 2 (P2) and 12 (P12). We used four paradigms that sample the input-output dependence on stimulation history in different but complementary ways: 1) paired-pulse depression; 2) steady-state depression during constant frequency trains; 3) modulation during irregular stimulation sequences; and 4) recovery after high-frequency conditioning trains. Paired-pulse synaptic depression declined more than steady-state depression during 10-pulse trains at frequencies from 0.125 to 8 Hz in this age range. Depression during sequences of irregular stimulations that more closely mimic physiological activation also declined with postnatal age. On the other hand, the overall rate of synaptic recovery after a 4-Hz conditioning train exhibited surprisingly little change between P2 and P12. Control experiments indicated that these observations depend primarily, if not exclusively, on changes in presynaptic transmitter release. The data were examined using quantitative models that incorporate factors that have been suggested to exist at more specialized central synapses. The model that best predicted the observations included two presynaptic compartments that are depleted during activation, plus two superimposed processes that enhance transmitter release by different mechanisms. One of the latter produced rapidly-decaying enhancement of transmitter release fraction. The other mechanism indirectly enhanced the rate of renewal of one of the depleted presynaptic compartments. This model successfully predicted the constant frequency and irregular sequence data from all age groups, as well as the recovery curves following short, high-frequency tetani. The results suggest that a reduction in release fraction accounts for much of the decline in synaptic depression during early postnatal development, although changes in both enhancement processes also contribute. The time constants of resource renewal showed surprisingly little change through the first 12 days of postnatal life.
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PMID:Developmental changes in short-term synaptic depression in the neonatal mouse spinal cord. 1246 42

Pattern of activity during development is important for the refinement of the final architecture of the brain. In the cerebellar cortex, the regression from multiple to single climbing fiber innervation of the Purkinje cell occurs during development between postnatal days (P) 5 and 15. However, the regression is hampered by altering in various ways the morpho-functional integrity of the parallel fiber input. In rats we disrupted the normal activity pattern of the climbing fiber, the terminal arbor of the inferior olive neurons, by administering harmaline for 4 days from P9 to P12. At all studied ages (P15-87) after harmaline treatment multiple (double only) climbing fiber EPSC-steps persist in 28% of cells as compared with none in the control. The ratio between the amplitudes of the larger and the smaller climbing fiber-evoked EPSC increases in parallel with the decline of the polyinnervation factor, indicating a gradual enlargement of the synaptic contribution of the winning climbing fiber synapse at the expense of the losing one. Harmaline treatment had no later effects on the climbing fiber EPSC kinetics and I/V relation in Purkinje cells (P15-36). However, there was a rise in the paired-pulse depression indicating a potentiation of the presynaptic mechanisms. In the same period, after harmaline treatment, parallel fiber-Purkinje cell electrophysiology was unaffected. The distribution of parallel fiber synaptic boutons was also not changed. Thus, a change in the pattern of activity during a narrow developmental period may affect climbing fiber-Purkinje cell synapse competition resulting in occurrence of multiple innervation at least up to 3 months of age. Our results extend the current view on the role of the pattern of activity in the refinement of neuronal connections during development. They suggest that many similar results obtained by different gene or receptor manipulations might be simply the consequence of disrupting the pattern of activity.
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PMID:A change in the pattern of activity affects the developmental regression of the Purkinje cell polyinnervation by climbing fibers in the rat cerebellum. 1456 18

Synapse maturation includes the shortening of postsynaptic currents, due to changes in the subunit composition of respective transmitter receptors. Patch clamp experiments revealed that GABAergic inhibitory postsynaptic currents (ISPCs) of superior colliculus neurons significantly shorten from postnatal day (P)1 to P21. The change started after P6 and was steepest between P12 and P15, i.e. around eye opening. It was accompanied by enhanced sensitivity to zolpidem and increased expression of GABAAR alpha1 mRNA, whereas the level of alpha3 mRNA decreased. This result is consistent with the hypothesis that the IPSC kinetics of developing collicular neurons is determined by the level of alpha1/alpha3. As alpha1/alpha3 peaked when N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents reached their maximum (P12) it was asked whether NMDAR activity can shape the kinetics of GABAergic IPSCs. Cultured collicular neurons were treated with NMDA or NMDAR block, and it was found that the former resulted in faster and the latter in slower IPSC decay. Group I mGluR blockade had no effect. Experiments with bdnf-/- mice revealed that, with some delay, the increase of alpha1/alpha3 mRNA also occurred in the chronic absence of brain-derived neurotrophic factor (BDNF) and, again, this was accompanied by the shortening of IPSCs. In addition, there was an age-dependent depression of IPSC amplitudes by endogenous BDNF, which might reflect the developmental increase in the expression of GABAAR gamma2L, as opposed to gamma2S. Together, these experiments suggest that the GABAAR alpha subunit switch and the associated change in the IPSC kinetics were specifically controlled by NMDAR activity and independent on the signalling through group I mGluRs or TrkB.
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PMID:GluR- and TrkB-mediated maturation of GABA receptor function during the period of eye opening. 1567 42

Within the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, there is a large central synapse known as the calyx of Held, which mediates high-fidelity glutamatergic transmission. We investigated the effects of congenital deafness on the development of pre- and postsynaptic parameters of synaptic strength at the calyx of Held. Whole cell recordings of evoked excitatory postsynaptic currents (EPSCs) and immunohistochemistry of GluR1-4 subunits were performed using brain stem slices from congenitally deaf or hearing mice at postnatal days P5 and P12. In both hearing and deaf mice there was a similar developmental decrease in the NMDA component of the evoked EPSC. There was a concurrent increase in release probability and number of release sites, contributing to a fivefold increase in evoked AMPA-mediated EPSC amplitude. The increase in release probability is opposite to that found in previous studies at the calyx of Held in the rat. There was also a seven- to eightfold increase in the size of the readily releasable pool of vesicles and a decrease in tetanic depression. The postsynaptic glutamate receptor subunits were similarly developmentally regulated and unaffected by deafness. GluR1 and 4 dominated at both ages. There was a decrease in expression of GluR1-3 from P5 to P12 and a shift from GluR2 to GluR3, indicating that AMPA receptor complexes at P12 are predominantly calcium-permeable. These results demonstrate that early development at this robust synapse proceeds normally with congenital deafness, suggesting that auditory nerve activity does not affect the development of synaptic strength at the calyx of Held.
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PMID:Development of a robust central auditory synapse in congenital deafness. 1600 May 24

We have characterized developmental changes in the kinetics and quantal parameters of action potential (AP)-evoked neurotransmitter release during maturation of the calyx of Held synapse. Quantal size (q) and peak amplitudes of evoked EPSCs increased moderately, whereas the fraction of vesicles released by single APs decreased. During synaptic depression induced in postnatal day (P) 5-7 synapses by 10-100 Hz stimulation, q declined rapidly to 40-12% of its initial value. The decrease in q was generally smaller in more mature synapses (P12-14), but quite severe for frequencies > or = 300 Hz. The stronger decline of q in immature synapses resulted from a slower recovery from desensitization, presumably due to delayed glutamate clearance. Recovery from this desensitization followed an exponential time course with a time constant of approximately 480 ms in P5-7 synapses, and sped up > 20-fold during maturation. Deconvolution analysis of EPSCs revealed a significant acceleration of the release time course during development, which was accompanied by a 2-fold increase of the peak release rate. During long 100 Hz trains, more mature synapses were able to sustain average rates of 8-10 quanta s(-1) per active zone for phasic release. The rates of asynchronous vesicle release increased transiently > 35-fold immediately after such stimuli and decayed rapidly with an exponential time constant of approximately 50 ms to low resting levels of spontaneous release. However, even following extended periods of 100 Hz stimulation, the amount of asynchronous release was relatively minor with peak rates of less than 5% of the average rate of synchronous release measured at steady state during the tetani. Therefore, a multitude of mechanisms seems to converge on the generation of fast, temporally precise and reliable high-frequency transmission at the mature calyx of Held synapse.
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PMID:Release kinetics, quantal parameters and their modulation during short-term depression at a developing synapse in the rat CNS. 1609 40

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


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