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

1. The properties of outward currents were investigated in acutely isolated dentate gyrus granule cells at postnatal ages of day 5-7, 10-14, 18-24 (P5-7, P10-14, P18-24) and at adulthood (2-3 mo), with the use of the whole-cell patch-clamp technique. 2. Kinetic analysis and pharmacological properties showed that an A-type K+ current (IA) and a delayed rectifier current (IK) were present in these cells. 3. IA in P10-14 cells activated and inactivated rapidly with a decay time constant of 7.5 +/- 2.1 (SD) ms with command pulses to +30 mV. The removal of inactivation was monoexponential with a time constant of 23.1 ms (holding potential, -50 mV; conditioning voltage steps of varying duration to -110 mV). V 1/2 of the Boltzmann function describing steady-state inactivation was -65.1 +/- 1.8 mV with a slope factor of -6.0. IA was sensitive to 5 mM 4-aminopyridine (4-AP) but not to 10 mM tetraethylammonium (TEA). 4. IK in P10-14 cells displayed a voltage-dependent activation time constant (4.3 +/- 0.8 ms for command pulses to +30 mV and 16.2 +/- 2.4 for command pulses to -10 mV) and a double-exponential decay (time constants 194 +/- 21 and 1,625 +/- 254 ms). The rate constant of removal of inactivation was 332.1 ms. IK showed a reduction by 61.4 +/- 5.3% with 10 mM TEA and was partially blocked by 5 mM 4-AP in a subpopulation of cells. 5. Whereas IA remained stable over time, IK showed a substantial reduction of current amplitude by 67% after 30 min of cell perfusion through the patch pipette. The time course of this reduction was monoexponential with a time constant of 6.9 min and was partly due to a shift in V1/2 of the steady-state inactivation from -79.2 to -99.6 mV. 6. IA and IK remained stable with respect to kinetic properties during ontogenesis. However, the relative contribution and pharmacological properties of the investigated K+ currents varied with age. Although IA dominated in P5-7 cells, IK was prominent in most older cells. Five millimolars 4-AP reduced IA by 40.7 +/- 26.7% in P5-7 cells and blocked IA completely in 80% of investigated P10-14 cells. Similar changes were observed for the effects of 4-AP on IK (18.7% depression in the age group P5-8, 46.1% in the age group P10-14, and 45.7% in adult animals).
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PMID:Properties of two voltage-activated potassium currents in acutely isolated juvenile rat dentate gyrus granule cells. 149 Dec 59

1. Whole cell recordings from layer V neurons of mouse somatosensory cortex were made with the use of a "blind" patch-clamp technique. In slices from immature [postnatal days 6 to 11 (P6-P11)] and juvenile (P18-P21) animals, inhibitory postsynaptic currents (IPSCs) were evoked in all cells by extracellular stimulation at the layer V-VI border. Monosynaptic IPSCs, with latency < 2 ms, were isolated pharmacologically by blockade of ionotropic glutamatergic transmission. IPSCs were blocked by bicuculline methiodide and reversed near the predicted equilibrium potential for Cl-. 2. IPSC characteristics were not different for the two age groups. At 1.5-2 times threshold intensity (0.2 Hz), they fluctuated in amplitude with occasional failures. At -70 or -80 mV, mean amplitudes were -202 +/- 20 (SE) pA and -207 +/- 32 pA for immature (39 cells) and juvenile (13 cells) cortex, respectively. Half rise times were 0.74 +/- 0.03 ms (n = 7 cells) in neonates and 0.67 +/- 0.04 ms (n = 7 cells) in juveniles. Decays were biexponential with tau 1 = 14.8 +/- 1.3 ms and tau 2 = 59.0 +/- 7.4 ms (n = 7 cells) in neonates, and tau 1 = 11.9 +/- 1.1 ms and tau 2 = 55.5 +/- 4.2 ms (n = 7 cells) in juveniles. 3. Pairs of stimuli elicited paired-pulse facilitation (PPF) when delivered at brief interstimulus intervals (ISI), and paired-pulse depression (PPD) at long ISI. PPF, which was evident in 64% of immature cells and 38% of juvenile cells, was maximal (38 +/- 4% greater than the conditioning response) at 20-40 ms. PPD, which was evident in 82% of immature cells and 87% of juvenile cells, was maximal (29 +/- 2% smaller than the conditioning response) by 300 ms. In each age group, some animals showed PPF without PPD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Paired-pulse facilitation of IPSCs in slices of immature and mature mouse somatosensory neocortex. 766 66

Intracellular and extracellular recordings were used to assess the cholinergic function in hippocampal slices from juvenile rats chronically deprived of NGF. NGF was neutralised by implanting into the lateral ventricle of postnatal (P) day 2 rats, alphaD11 hybridoma cells (secreting monoclonal antibodies specific for NGF). Parental myeloma cells (P3U) were used as controls. At P15-P18, slow cholinergic EPSPs could be elicited in cells from both alphaD11- and P3U-treated rats. However, slices from alphaD11-implanted rats exhibited a 50% reduction in acetylcholine release following stimulation of cholinergic fibres. This effect was associated to a significant increase in the sensitivity of pyramidal cells to carbachol, as suggested by the shift to the left of the dose/response curve. This may reflect a compensatory mechanism for the reduced efficacy of cholinergic innervation in NGF-deprived rats. In both alphaD11- and P3U-treated rats, carbachol was able to induce a similar concentration-dependent depression of the field EPSPs, evoked by Schaffer collateral stimulation, suggesting that presynaptic muscarinic receptors were not altered. In rats implanted with alphaD11 cells at P15 and sacrificed at P21-P24, no changes in the sensitivity to carbachol were found. At this developmental stage, no differences in acetylcholine release were observed between P3U- and alphaD11-treated animals. These results provide physiological evidence for a regulatory role of NGF in the cholinergic function of the hippocampus during postnatal development.
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PMID:Cholinergic function in the hippocampus of juvenile rats chronically deprived of NGF. 972 37

beta2-Laminin is important for the formation of neuromuscular junctions in vertebrates. Previously, we have inactivated the gene that encodes for beta2-laminin in mice and observed predominantly prejunctional structural defects. In this study, we have used both intra- and extracellular recording methods to investigate evoked neurotransmission in beta2-laminin-deficient mice, from postnatal day 8 (P8) through to day 18 (P18). Our results confirmed that there was a decrease in the frequency of spontaneous release, but no change in the postjunctional response to such release. Analysis of evoked neurotransmission showed an increase in the frequency of stimuli that failed to elicit an evoked postjunctional response in the mutants compared to litter mate controls, resulting in a 50 % reduction in mean quantal content at mutant terminals. Compared to littermate controls, beta2-laminin-deficient terminals showed greater synaptic depression when subjected to high frequency stimulation. Furthermore, the paired pulse ratio of the first two stimuli was significantly lower in beta2-laminin mutant terminals. Statistical analysis of the binomial parameters of release showed that the decrease in quantal content was due to a decrease in the number of release sites without any significant change in the average probability of release. This suggestion was supported by the observation of fewer synaptic vesicle protein 2 (SV2)-positive varicosities in beta2-laminin-deficient terminals and by ultrastructural observations showing smaller terminal profiles and increased Schwann cell invasion in beta2-laminin mutants; the differences between beta2-laminin mutants and wild-type mice were the same at both P8 and P18. From these results we conclude that beta2-laminin plays a role in the early structural development of the neuromuscular junction. We also suggest that transmitter release activity may act as a deterrent to Schwann cell invasion in the absence of beta2-laminin.
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PMID:Functional analysis of neurotransmission at beta2-laminin deficient terminals. 1256 4

Low-frequency stimulation (LFS) is used to induce long-term depression (LTD) and depotentiation at rodent CA3-CA1 hippocampal synapses. The relationship between the efficacy of LFS induction and postnatal age remains to be clearly defined in rat and had not been studied in mouse. The data presented here show that in acute mouse hippocampal slices LFS-induced LTD and depotentiation at CA3-CA1 synapses are: synapse specific; NMDA receptor-dependent; and metabotropic glutamate (mGlu) receptor type I/II independent. Furthermore LFS-induced LTD is highly age-dependent whilst long-term potentiation (LTP) and depotentiation are not. In slices from very young mice (P6-9) LFS induced a robust and stable LTD (-31.1 +/- 5.9%, n = 8, P < 0.01) of CA1 field excitatory post-synaptic potentials (fEPSPs), measured 55-60 min after conditioning. LFS also induced LTD in slices from mice aged P10-13 and P14-17 (-16.0 +/- 3.0%, n = 35, P < 0.001 and -17.9 +/- 5.5%, n = 12, P < 0.01, respectively). However, LTD was not expressed in slices from animals aged P18-21 ( -7.0 +/- 4.1%, n = 16, P > 0.05) or older.
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PMID:Bi-directional plasticity and age-dependent long-term depression at mouse CA3-CA1 hippocampal synapses. 1530 85

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

Kainate type of glutamate receptors (KARs) modulate synaptic transmission in a developmentally regulated manner at several synapses in the brain. Previous studies have shown that KARs depress glutamatergic transmission at CA3-CA1 synapses in the hippocampus and these receptors are tonically active during early postnatal development. Here we use the GluR5 subunit specific agonist ATPA to further characterize the role of KARs in the modulation of synaptic transmission and plasticity in area CA1 during the first two weeks of life. We find that the depressant effect of ATPA on evoked fEPSPs/EPSCs is smaller in the neonate (P3-P6) than in the juvenile (P14-P18) rat CA1, due to endogenous activity of KAR in the neonate. Further, in the neonate but not juvenile CA1, ATPA downregulates action-potential independent transmission (mEPSCs) and its effects are dependent on protein kinase C activity. ATPA-induced depression of fEPSPs in the neonate occludes the presynaptic component of long-term depression (LTD). In contrast, at P14-P18, ATPA prevents LTD indirectly via GABAergic mechanisms. These data show that GluR5 signaling mechanisms are developmentally regulated and suggest distinct functional role for KARs in the modulation of synaptic transmission and plasticity at different stages of development.
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PMID:Effects of the kainate receptor agonist ATPA on glutamatergic synaptic transmission and plasticity during early postnatal development. 1739 19

Synaptic strength is determined by release probability and the size of the readily releasable pool of docked vesicles. Here we describe the effects of blocking myosin light chain kinase (MLCK), a cytoskeletal regulatory protein thought to be involved in myosin-mediated vesicle transport, on synaptic transmission at the mouse calyx of Held synapse. Application of three different MLCK inhibitors increased the amplitude of the early excitatory postsynaptic currents (EPSCs) in a stimulus train, without affecting the late steady-state EPSCs. A presynaptic locus of action for MLCK inhibitors was confirmed by an increase in the frequency of miniature EPSCs that left their average amplitude unchanged. MLCK inhibition did not affect presynaptic Ca(2+) currents or action potential waveform. Moreover, Ca(2+) imaging experiments showed that [Ca(2+)](i) transients elicited by 100-Hz stimulus trains were not altered by MLCK inhibition. Studies using high-frequency stimulus trains indicated that MLCK inhibitors increase vesicle pool size, but do not significantly alter release probability. Accordingly, when AMPA-receptor desensitization was minimized, EPSC paired-pulse ratios were unaltered by MLCK inhibition, suggesting that release probability remains unaltered. MLCK inhibition potentiated EPSCs even when presynaptic Ca(2+) buffering was greatly enhanced by treating slices with EGTA-AM. In addition, MLCK inhibition did not affect the rate of recovery from short-term depression. Finally, developmental studies revealed that EPSC potentiation by MLCK inhibition starts at postnatal day 5 (P5) and remains strong during synaptic maturation up to P18. Overall, our data suggest that MLCK plays a crucial role in determining the size of the pool of synaptic vesicles that undergo fast release at a CNS synapse.
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PMID:The pool of fast releasing vesicles is augmented by myosin light chain kinase inhibition at the calyx of Held synapse. 1825 66

We investigated the development of L2/3 pyramidal cell (PC) circuitry in juvenile mice from postnatal day 10 (P10) to P29. Using whole cell recordings in an in vitro thalamocortical slice preparation, we examined the connection architecture and intrinsic and synaptic properties of PCs. The excitatory connections between PCs were highly localized: the probability of connection between PCs declined with intersomatic distance from 0.18 to about 0.05 over 150 microm, but did not vary with age. However, the mean and variance of the intrinsic and synaptic properties of PCs changed dramatically between P10 and P29. The input resistance, membrane time constant, and resting membrane potential decreased, leading to reduced neural excitability in older animals. Likewise, there were age-dependent decreases in the amplitude and decay time of the excitatory postsynaptic potentials as well as short-term synaptic depression. Both the intrinsic and synaptic properties underwent a transitional period between P10 and P18 prior to reaching steady state at P19-P29. We show that these properties combine to produce age-related differential synaptic responses to low- and high-frequency synaptic input that may contribute to differences in auditory processing during development.
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PMID:Maturation of intrinsic and synaptic properties of layer 2/3 pyramidal neurons in mouse auditory cortex. 1841 31

Mutations in the gene that encodes espins can cause deafness and vestibular disorders; mice that are homozygous for the autosomal recessive jerker mutation in the espin gene never hear. Extracellular injections of biocytin into the anteroventral cochlear nucleus (AVCN) revealed that although the cochlear nuclei are smaller in je/je mice, the topography in its innervation resembles that in wild-type mice. Auditory nerve fibers innervate narrow, topographically organized, "isofrequency" bands in deaf animals over the ages examined, P18-P70. The projection of tuberculoventral cells was topographic in je/je as in wild-type mice. Terminals of auditory nerve fibers in the multipolar cell area included both large and small endings, whereas in the octopus cell area they were exclusively small boutons in je/je as in wild-type mice, but end bulbs near the nerve root of je/je animals were smaller than in hearing animals. In whole-cell recordings from targets of auditory nerve fibers, octopus and T stellate cells, miniature excitatory postsynaptic currents (mEPSCs) had similar shapes as in +/+, indicating that the properties of AMPA receptors were not affected by the mutation. In je/je animals the frequency of spontaneous mEPSCs was elevated, and synaptic depression in responses to trains of shocks delivered at between 100 and 333 Hz was greater than in wild-type mice, indicating that the probability of neurotransmitter release was increased. The frequency of spontaneous mEPSCs and extent of synaptic depression were greater in octopus than in T stellate cells, in both wild-type and in je/je mice.
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PMID:Connections and synaptic function in the posteroventral cochlear nucleus of deaf jerker mice. 1863 2


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