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Results for “synaptic plasticity”

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At least 559 records · Page 31Linked to original sources
PubMed1998

Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: effects of insulin treatment.

Streptozotocin-diabetic rats express deficits in water maze learning and hippocampal synaptic plasticity. The present study examined whether these deficits could be prevented and/or reversed with insulin treatment. In addition, the water maze learning deficit in diabetic rats was further characterized. Insulin treatment was commenced at the onset of diabetes in a prevention experiment, and 10 weeks after diabetes induction in a reversal experiment. After 10 weeks of treatment, insulin-treated diabetic rats, untreated diabetic rats and non-diabetic controls were tested in a spatial version of the Morris water maze. Next, hippocampal long-term potentiation (LTP) was measured in vitro. To further characterize the effects of diabetes on water maze learning, a separate group of rats was pre-trained in a non-spatial version of the maze, prior to exposure to the spatial version. Both water maze learning and hippocampal LTP were impaired in diabetic rats. Insulin treatment commenced at the onset of diabetes prevented these impairments. In the reversal experiment, insulin treatment failed to reverse established deficits in maze learning and restored LTP only partially. Non-spatial pre-training abolished the performance deficit of diabetic rats in the spatial version of the maze. It is concluded that insulin treatment may prevent but not reverse deficits in water maze learning and LTP in streptozotocin-diabetic rats. The pre-training experiment suggests that the performance deficit of diabetic rats in the spatial version of the water maze is related to difficulties in learning the procedures of the maze rather than to impairments of spatial learning.

Animals↗
PubMed2000

[Synaptic plasticity and neuromodulation of local cortical connections].

Long-term potentiation (LTP) and long-term depression (LTD) represent two forms of synaptic plasticity which may act as mechanisms for reorganizations of adult mammalian motor cortex. Layer II/III horizontal connections may form a substrate for these reorganizations. The induction of LTP in these connections requires conjoint activation of cortical layer V or layer I. The activity of the cholinergic system facilitates LTP induction.

Acetylcholine↗
PubMed2002

Spike timing, calcium signals and synaptic plasticity.

Plasticity at central synapses depends critically on the timing of presynaptic and postsynaptic action potentials. Key initial steps in synaptic plasticity involve the back-propagation of action potentials into the dendritic tree and calcium influx that depends nonlinearly on the action potential and synaptic input. These initial steps are now better understood. In addition, recent studies of processes as diverse as gene expression and channel inactivation suggest that responses to calcium transients depend not only their amplitude, but on their time course and on the location of their origin.

Action Potentials↗
PubMedDate not supplied

The effects of forelimb deafferentation on the post-natal development of synaptic plasticity in the hippocampus.

The effects of partial deafferentation of the forelimb on the development of long-term potentiation in the hippocampus of rats aged 13-18 days were studied. Long-term potentiation in hippocampus field CA1 was of greater amplitude and duration in control rats at 16-18 days of post-natal ontogenesis than in adult animals. Partial deafferentation by section of the median nerve in the forelimb on the 13th day of life led to the disappearance of this excess at 16-18 days. The peak in synaptic plasticity occurred later in operated animals--on day 17--and was much less marked than in controls. The decreases in the amplitude and duration of long-term potentiation in hippocampal field CA1 in operated animals provides evidence for a decrease in the sensitivity and/or number of NMDA receptors. This suggests that partial deafferentation of one limb may lead not to a decrease but to an increase in spike and synaptic activity in the hippocampus, which in normal conditions may affect the maturation of the plastic properties of synaptic transmission associated with the expression and positions of NMDA receptors. The level of long-term potentiation in sham-operated rats was significantly greater than in controls of the same age. This significant increase in NMDA-dependent long-term potentiation may be explained by a decrease in the level of activation due to anesthesia. It is suggested that the decrease in the spike activity of cells receiving signals from the median nerve may be compensated for by activation of other specific and non-specific inputs.

Aging↗
PubMed1996

Experience-dependent modification of synaptic plasticity in visual cortex.

In many regions of the cerebral cortex, Ca2+ influx through NMDA (N-methyl-D-aspartate) sensitive glutamate receptors (NMDA receptors) can trigger two forms of synaptic plasticity: long-term depression (LTD) and long-term potentiation (LTP). LTD is induced by low levels of postsynaptic NMDA-receptor activation, for instance in response to low-frequency stimulation, whereas LTP is induced by the stronger activation that occurs following high-frequency stimulation. Theoretical studies have shown that the properties of synaptic LTD and LTP can account for many aspects of experience-dependent plasticity in the developing visual cortex, provided that the LTD-LTP crossover point (the modification threshold, theta(m)) varies as a function of the history of cortical activity. Here we provide direct experimental evidence that the value of theta(m) depends on sensory experience. We find in visual cortex of light-deprived rats that LTP is enhanced and LTD diminished over a range of stimulation frequencies, and that these effects can be reversed by as little as two days of light exposure. Our findings support the idea that a variable synaptic modification threshold allows synaptic weights in neural networks to achieve a stable equilibrium.

Animals↗
PubMedDate not supplied

The cortico-basal ganglia-thalamocortical circuit with synaptic plasticity. I. Modification rules for excitatory and inhibitory synapses in the striatum.

It is pointed out that Ca(2+)-dependent modification rules for NMDA-dependent (NMDA-independent) synaptic plasticity in the striatum are similar to those in the neocortex and hippocampus (cerebellum). A unitary postsynaptic mechanism of synaptic modification is proposed. It is based on the assumption that, in diverse central nervous system structures, long-term potentiation/depression (LTP/LTD) of excitatory transmission (depression/potentiation of inhibitory transmission, LTDi/LTPi) is the result of an increasing/decreasing the number of phosphorylated AMPA and NMDA (GABA(A)) receptors. According to the suggested mechanism, Ca(2+)/calmodulin-dependent protein kinase II and protein kinase C, whose activity is positively correlated with Ca(2+) enlargement, together with cAMP-dependent protein kinase A (cGMP-dependent protein kinase G, whose activity is negatively correlated with Ca(2+) rise) mainly phosphorylate ionotropic striatal receptors, if NMDA channels are opened (closed). Therefore, the positive/negative post-tetanic Ca(2+) shift in relation to a previous Ca(2+) rise must cause NMDA-dependent LTP+LTDi/LTD+LTPi or NMDA-independent LTD+LTPi/LTP+LTDi. Dopamine D(1)/D(2) or adenosine A(2A)/A(1) receptor activation must facilitate LTP+LTDi/LTD+LTPi due to an augmenting/lowering PKA activity. Activation of muscarinic M(1)/M(4) receptors must enhance LTP+LTDi/LTD+LTPi as a consequence of an increase/decrease in the activity of protein kinase C/A. The proposed mechanism is in agreement with known experimental data.

Acetylcholine↗
PubMed1994

Flip side of synaptic plasticity: long-term depression mechanisms in the hippocampus.

There is growing interest in the phenomenon of long-term depression (LTD) of synaptic efficacy that, together with long-term potentiation (LTP), is a putative information storage mechanism in mammalian brain. In neural network models, multiple learning rules have been used for LTD induction. Similarly, in neurophysiological studies of hippocampal synaptic plasticity, a variety of activity patterns have been effective at inducing LTD, although experimental paradigms are still being optimized. In this review the authors summarize the major experimental paradigms and compare what is known about the mechanisms of LTD induction. Although all paradigms appear to initiate a cascade of events leading to an elevated level of Ca2+ postsynaptically, the extent to which these paradigms involve common expression mechanisms has not yet been tested. The authors discuss several critical experiments that would address this latter issue. Numerous questions about the properties and mechanisms of LTD(s) in the hippocampus remain to be answered, but it is clear that LTD has finally arrived, and will soon be attracting attention equal to its flip side, LTP.

Animals↗
PubMed2006

Enriched environment treatment restores impaired hippocampal synaptic plasticity and cognitive deficits induced by prenatal chronic stress.

Prenatal stress can cause long-term effects on cognitive functions in offspring. Hippocampal synaptic plasticity, believed to be the mechanism underlying certain types of learning and memory, and known to be sensitive to behavioral stress, can be changed by prenatal stress. Whether enriched environment treatment (EE) in early postnatal periods can cause a recovery from these deficits is unknown. Experimental animals were Wistar rats. Prenatal stress was evoked by 10 foot shocks (0.8 mA for 1s, 2-3 min apart) in 30 min per day at gestational day 13-19. After weaning at postnatal day 22, experimental offspring were given the enriched environment treatment through all experiments until tested (older than 52 days age). Electrophysiological and Morris water maze testing was performed at 8 weeks of age. The results showed that prenatal stress impaired long-term potentiation (LTP) but facilitated long-term depression (LTD) in the hippocampal CA1 region in the slices. Furthermore, prenatal stress exacerbated the effects of acute stress on hippocampal LTP and LTD, and also impaired spatial learning and memory in the Morris water maze. However, all these deficits induced by prenatal stress were recovered by enriched environment treatment. This work observes a phenomenon that may contribute to the understanding of clinically important interactions among cognitive deficit, prenatal stress and enriched environment treatment. Enriched environment treatment on early postnatal periods may be one potentially important target for therapeutic interventions in preventing the prenatal stress-induced cognitive disorders.

Animals↗
PubMed2006

Synaptic plasticity: one STEP at a time.

Striatal enriched tyrosine phosphatase (STEP) has recently been identified as a crucial player in the regulation of synaptic function. It is restricted to neurons within the CNS and acts by downregulating the activity of MAP kinases, the tyrosine kinase Fyn and NMDA receptors. By modulating these substrates, STEP acts on several parallel pathways that impact upon the progression of synaptic plasticity. Here, we review recent advances that demonstrate the importance of STEP in normal cognitive function, and its possible involvement in cognitive disorders such as Alzheimer's disease.

Animals↗
PubMed2004

Acute exposure to CXC chemokine ligand 10, but not its chronic astroglial production, alters synaptic plasticity in mouse hippocampal slices.

Brain levels of CXC chemokine ligand 10 (CXCL10) are elevated in a number of neuropathological conditions. To determine its impact on neuronal function, we measured synaptic transmission and plasticity in hippocampal slices prepared from transgenic (TG) mice with chronic astroglial production of CXCL10. We also tested the acute effect of recombinant CXCL10 applied to slices from normal C57Bl/6J mice, CXCL10 TG mice and CXCR3 knock out (KO) mice. Chronic production of CXCL10 did not alter synaptic plasticity. By contrast, exogenous CXCL10 (10 ng/ml) significantly inhibited long-term potentiation (LTP) in slices from normal C57Bl/6J mice and CXCL10 TG. The effect was probably receptor-mediated because CXCL10-induced inhibition of LTP was not observed in CXCR3 KO mice. Our findings suggest that acute exposure to CXCL10 alters synaptic plasticity via CXCR3 in mouse hippocampus.

Animals↗
PubMed2006

Beta 1-integrins are required for hippocampal AMPA receptor-dependent synaptic transmission, synaptic plasticity, and working memory.

Integrins comprise a large family of cell adhesion receptors that mediate diverse biological events through cell-cell and cell-extracellular matrix interactions. Recent studies have shown that several integrins are localized to synapses with suggested roles in synaptic plasticity and memory formation. We generated a postnatal forebrain and excitatory neuron-specific knock-out of beta1-integrin in the mouse. Electrophysiological studies demonstrated that these mutants have impaired synaptic transmission through AMPA receptors and diminished NMDA receptor-dependent long-term potentiation. Despite the impairment in hippocampal synaptic transmission, the mutants displayed normal hippocampal-dependent spatial and contextual memory but were impaired in a hippocampal-dependent, nonmatching-to-place working memory task. These phenotypes parallel those observed in animals carrying knock-outs of the GluR1 (glutamate receptor subunit 1) subunit of the AMPA receptor. These observations suggest a new function of beta1-integrins as regulators of synaptic glutamate receptor function and working memory.

Animals↗
PubMed1988

The development of transmission at an identified molluscan synapse. I. The emergence of synaptic plasticities.

1. A monosynaptic, chemical synapse exists between two identified neurons in the subesophageal ganglia of the pulmonate mollusc, Achatina fulica. The snail undergoes a direct development, i.e., there is no intervening metamorphic period. The presynaptic (V2) and postsynaptic (RPr1) cells are two of the largest neurons found in the ganglia. The development of transmission at this synapse was studied from the last one-third of embryonic life to adulthood. 2. Synaptic transmission was studied by eliciting an action potential in V2 and recording the resultant excitatory postsynaptic potential (EPSP) in RPr1. In a train of repetitive stimuli, the ratio of the mean amplitude of the second EPSP to that of the first EPSP (EPSP2/EPSP1) is always greater than 1, indicating that short-term facilitation is present at all developmental ages studied. Following the initial short-term facilitation, embryonic synapses undergo a profound synaptic depression. Postembryonically there is a progressive increase in the amount of frequency facilitation with age, suggesting that the synapse shows a developmental trend towards an increased capacity for transmitter release. 3. In contrast to the progressive growth of frequency facilitation, the amplitude of the first EPSP in a series of responses (EPSP1) is not significantly related to age. 4. When transmitter release is reduced to approximately 25% of normal levels by a low-Ca2+/high-Mg2+ saline, the synaptic depression that is observed in the younger synapses disappears and is replaced by an adult-like frequency facilitation. 5. The adult synapse displays a phenomenon similar to posttetanic potentiation, which we refer to as the "retention of frequency facilitation." If an initial train of 150 stimuli at 0.2 Hz is followed by a second, identical train after an interval of 1 h, the postsynaptic response is greater during the second train than during the first. This phenomenon only becomes apparent in the second month after hatching, indicating that this separate synaptic plasticity develops at a different rate than does frequency facilitation.

Animals↗
PubMed2005

Phosphorylation of AMPA receptors: mechanisms and synaptic plasticity.

The ionotropic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor is densely distributed in the mammalian brain and is primarily involved in mediating fast excitatory synaptic transmission. Recent studies in both heterologous expression systems and cultured neurons have shown that the AMPA receptor can be phosphorylated on their subunits (GluR1, GluR2, and GluR4). All phosphorylation sites reside at serine, threonine, or tyrosine on the intracellular C-terminal domain. Several key protein kinases, such as protein kinase A, protein kinase C, Ca2+/calmodulin-dependent protein kinase II, and tyrosine kinases (Trks; receptor or nonreceptor family Trks) are involved in the site-specific regulation of the AMPA receptor phosphorylation. Other glutamate receptors (N-methyl-d-aspartate receptors and metabotropic glutamate receptors) also regulate AMPA receptors through a protein phosphorylation mechanism. Emerging evidence shows that as a rapid and short-term mechanism, the dynamic protein phosphorylation directly modulates the electrophysiological, morphological (externalization and internalization trafficking and clustering), and biochemical (synthesis and subunit composition) properties of the AMPA receptor, as well as protein-protein interactions between the AMPA receptor subunits and various intracellular interacting proteins. These modulations underlie the major molecular mechanisms that ultimately affect many forms of synaptic plasticity.

Amino Acid Sequence↗
PubMed1996

Impaired cerebellar synaptic plasticity and motor performance in mice lacking the mGluR4 subtype of metabotropic glutamate receptor.

The application of the glutamate analog L-2-amino-4-phosphonobutyric acid (L-AP4) to neurons produces a suppression of synaptic transmission. Although L-AP4 is a selective ligand at a subset of metabotropic glutamate receptors (mGluRs), the precise physiological role of the L-AP4-activated mGluRs remains primarily unknown. To provide a better understanding of the function of L-AP4 receptors, we have generated and studied knockout (KO) mice lacking the mGluR4 subtype of mGluR that displays high affinity for L-AP4. The mGluR4 mutant mice displayed normal spontaneous motor activity and were unimpaired on the bar cross test, indicating that disruption of the mGluR4 gene did not cause gross motor abnormalities, impairments of novelty-induced exploratory behaviors, or alterations in fine motor coordination. However, the mutant mice were deficient on the rotating rod motor-learning test, suggesting that mGluR4 KO mice may have an impaired ability to learn complex motor tasks. Patch-clamp and extracellular field recordings from Purkinje cells in cerebellar slices demonstrated that L-AP4 had no effect on synaptic responses in the mutant mice, whereas in the wild-type mice 100 microM L-AP4 produced a 23% depression of synaptic responses with an EC50 of 2.5 microM. An analysis of presynaptic short-term synaptic plasticity at the parallel fiber-->Purkinje cell synapse demonstrated that paired-pulse facilitation and post-tetanic potentiation were impaired in the mutant mice. In contrast, long-term depression (LTD) was not impaired. These results indicate that an important function of mGluR4 is to provide a presynaptic mechanism for maintaining synaptic efficacy during repetitive activation. The data also suggest that the presence of mGluR4 at the parallel fiber-->Purkinje cell synapse is required for maintaining normal motor function.

Animals↗
PubMed2004

Does the fusion pore contribute to synaptic plasticity?

How synapses change their strength in response to impinging neural activity is a fundamental issue for understanding how the brain molds its circuitry in response to behavioral experience. Although a growing number of studies reveal the involvement of postsynaptic changes contributing to synaptic plasticity in brain circuits, the involvement of presynaptic factors has been implied by several studies. Most recently, several works point to the mechanism of vesicle fusion as a new possible locus for the modification of presynaptic synaptic strength. However, it is not yet clear to what extent such changes affect the simplest form of information transfer in the brain--the transmission of a single action potential.

Animals↗
PubMed2006

Optical induction of synaptic plasticity using a light-sensitive channel.

We have combined millisecond activation of channelrhodopsin-2 (ChR2), a light-gated ion channel, with two-photon calcium imaging to investigate active synaptic contacts in rat hippocampal slice cultures. Calcium influx was larger during light-induced action potentials than during action potentials induced by somatic current injection, leading to highly reproducible synaptic transmission. Pairing of light stimulation with postsynaptic depolarization induced long-term potentiation, making this technique ideal for genetic and pharmacological dissection of synaptic plasticity.

Action Potentials↗
PubMed2001

The role of N-methyl-D-aspartate receptors in synaptic plasticity of rat visual cortex in vitro: effect of sensory experience.

We examined the role of N-methyl-D-aspartate (NMDA) receptors in synaptic plasticity of visual cortex of light (LR) and dark (DR) reared adult rats in vitro. Layer IV stimulation resulted in field potentials in layer II/III, consisting of two excitatory postsynaptic potentials (EPSP) called EPSP1 and EPSP2. Tetanic stimulation induced long-term potentiation (LTP) in EPSP2 of both LR and DR visual cortices. NMDA receptor antagonist D, L-2-amino-5-phosphono-valeric acid (AP5) completely blocked the LTP of EPSP2 in DR visual cortex while it reduced slightly the extent of LTP of EPSP2 in LR ones. Another NMDA receptor antagonist ketamine blocked potentiation of EPSP1 as well as EPSP2 in both groups. Our findings demonstrate that dependency of LTP on NMDA receptors and/or sensitivity of these receptors to the antagonists are different in LR and DR animals.

2-Amino-5-phosphonovalerate↗
PubMed2005

The neuronal death protein par-4 mediates dopaminergic synaptic plasticity.

Par-4, discovered in a screen for genes whose expression is increased in prostate tumor cells undergoing apoptosis, participates in physiological and pathological nerve cell death. A new study, however, provides evidence for an unexpected role for Par-4 in regulating synaptic transmission in the brain: Par-4 binds to the D2 dopamine receptor (D2DR) and modulates its activity. Mice in which the function of Par-4 is disrupted exhibit impaired dopaminergic neurotransmission, resulting in a depression-like syndrome. Several other cell death-related proteins also appear to function in regulating synaptic plasticity, suggesting that a better understanding of the functions of these proteins may lead to novel therapeutic approaches for a psychiatric and neurodegenerative disorders.

Animals↗