Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “synaptic plasticity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1997

Chronic hypoxia does not induce synaptic plasticity in the phrenic nucleus.

Interruption of the main descending respiratory drive to phrenic motoneurons by cold block or spinal cord hemisection results in morphological modifications of the ipsilateral phrenic nucleus in the rat. The modifications consist of an increase in the number of multiple synapses and dendrodendritic appositions and elongation of the asymmetric and symmetric synaptic active zones. Hemisection and hemispinalization by cold block cause not only "functional deafferentation" of the ipsilateral phrenic neurons (i.e., a loss of ipsilateral descending respiratory drive), but also an increase in the remaining contralateral descending respiratory drive. The contralateral respiratory pathways connect with phrenic motoneurons ipsilateral to cold block or hemisection by decussating collateral axons which cross the spinal cord midline below the hemisection/cold block site. Thus, the phrenic nucleus synaptic plasticity could possibly be induced by functional deafferentation or by an increase of the descending respiratory drive. To differentiate between these two possible inducers of the plasticity, we assessed the synaptic morphology of the phrenic nucleus of nonoperated rats exposed to 48 h of hypoxia in an atmosphere chamber. The hypoxia exposure produces an increased descending respiratory drive without functional deafferentation. The quantitative data extracted from electron micrographs of the phrenic nucleus from four experimental rats were compared with the data from four normal breathing animals. Phrenic nucleus morphometric analysis showed that there was no significant difference in the mean number of single synapses between the samples from control animals (141 +/- 12.12) and the experimental animals (156 +/- 26.73). Similarly, no significant difference was detected in the total number of synaptic active zones of control animals (178.25 +/- 11.13) and experimental animals (195.05 +/- 5.35). Furthermore, the length of synaptic active zones of asymmetrical synapses (0.21 +/- 0.024 micron) or symmetrical synapses (0.22 +/- 0.022 micron) did not change significantly compared to the synaptic active zone length in control animals (0.21 +/- 0.018 micron for asymmetrical and 0.21 +/- 0.010 micron for symmetrical). We conclude that no synaptic plasticity occurs in the phrenic nucleus without functional deafferentation in spite of an increase in descending respiratory drive. Therefore functional deafferentation may be the primary inducer of phrenic nucleus synaptic plasticity occurring after hemisection or cold block.

Animals↗
PubMedDate not supplied

Synaptic plasticity and learning and memory: 15 years of progress.

Much has been learned over the past 15 years about the mechanisms of synaptic plasticity and their relationships to learning and memory processes. Some of the questions raised 15 years ago have been answered while others still remain elusive. This brief review attempts to evaluate the progress accomplished in this field and discusses four specific issues: (i) the relationships between mechanisms of synaptic plasticity and memory types, (ii) the relationships between stabilization of synaptic modifications and memory consolidation, (iii) the links between gene regulation and regulation of synaptic efficacy, and (iv) the relationships between synaptic dynamics and synaptic plasticity. Although it is relatively easy to identify areas in which progress has been made, it is also clear that many areas remain highly controversial and will keep neuroscientists busy for years to come.

Animals↗
PubMed2001

Rab3A is required for brain-derived neurotrophic factor-induced synaptic plasticity: transcriptional analysis at the population and single-cell levels.

Brain-derived neurotrophic factor (BDNF) modulates synaptic strength in hippocampal neurons, in addition to promoting survival and differentiation. To identify genes involved in trophic regulation of synaptic plasticity, we have used a multidisciplinary approach of differential display and family-specific slot blots in combination with whole-cell patch-clamp recordings of dissociated hippocampal neurons. Three hour exposure to BDNF elicited a 2.6-fold increase in synaptic charge and a concomitant induction of 11 genes as revealed by differential display, including the small GTP-binding vesicular trafficking protein Rab3A and the enzyme guanylate cyclase (GC). Slot blot analysis on a population of neurons confirmed an average of 3.1-fold induction of these clones. In contrast, individual pyramidal-like neurons that were first characterized electrophysiologically in the presence of BDNF and subjected to transcriptional analysis displayed more robust increases (4.8-fold), emphasizing the neuronal heterogeneity. Transcriptional changes of Rab3A and GC were accompanied by translational regulation, shown by Western blot analysis. Furthermore, a number of GC-associated and Rab3A effector molecules were induced by BDNF at either the gene or protein levels. The functional role of Rab3A in BDNF-induced synaptic plasticity was assessed using cells derived from Rab3A knock-out mice. These neurons failed to show an increase in synaptic charge in response to BDNF at 10 min; however a late response to BDNF was detected at 20 min. This late response was similar in time course to that induced by postsynaptic activation of glutamate receptors. Our results demonstrate a requirement for Rab3A and may reveal a temporal distinction between presynaptic and postsynaptic mechanisms of BDNF-induced synaptic plasticity associated with learning and memory.

Animals↗
PubMed2004

Increased neuronal excitability, synaptic plasticity, and learning in aged Kvbeta1.1 knockout mice.

BACKGROUND: Advancing age is typically accompanied by deficits in learning and memory. These deficits occur independently of overt pathology and are often considered to be a part of "normal aging." At the neuronal level, normal aging is known to be associated with numerous cellular and molecular changes, which include a pronounced decrease in neuronal excitability and an altered induction in the threshold for synaptic plasticity. Because both of these mechanisms (neuronal excitability and synaptic plasticity) have been implicated as putative cellular substrates for learning and memory, it is reasonable to propose that age-related changes in these mechanisms may contribute to the general cognitive decline that occurs during aging. RESULTS: To further investigate the relationship between aging, learning and memory, neuronal excitability, and synaptic plasticity, we have carried out experiments with aged mice that lack the auxiliary potassium channel subunit Kvbeta1.1. In aged mice, the deletion of the auxiliary potassium channel subunit Kvbeta1.1 resulted in increased neuronal excitability, as measured by a decrease in the post-burst afterhyperpolarization. In addition, long-term potentiation (LTP) was more readily induced in aged Kvbeta1.1 knockout mice. Finally, the aged Kvbeta1.1 mutants outperformed age-matched controls in the hidden-platform version of the Morris water maze. Interestingly, the enhancements in excitability and learning were both sensitive to genetic background: The enhanced learning was only observed in a genetic background in which the mutants exhibited increased neuronal excitability. CONCLUSIONS: Neuronal excitability is an important determinant of both synaptic plasticity and learning in aged subjects.

Action Potentials↗
PubMedDate not supplied

Ca2+ and synaptic plasticity.

The induction and maintenance of synaptic plasticity is well established to be a Ca2+-dependent process. The use of fluorescent imaging to monitor changes [Ca2+]i in neurones has revealed a diverse array of signaling patterns across the different compartments of the cell. The Ca2+ signals within these compartments are generated by voltage or ligand-gated Ca2+ influx, and release from intracellular stores. The changes in [Ca2+]i are directly linked to the activity of the neurone, thus a neurone's input and output is translated into a dynamic Ca2+ code. Despite considerable progress in measuring this code much still remains to be determined in order to understand how the code is interpreted by the Ca2+ sensors that underlie the induction of compartment-specific plastic changes.

Animals↗
PubMed2007

Sources and targets of reactive oxygen species in synaptic plasticity and memory.

Increasing evidence suggests that reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, act as necessary signaling molecules in processes underlying cognition. Moreover, ROS have been shown to be necessary in molecular process underlying signal transduction, synaptic plasticity, and memory formation. Research from several laboratories suggests that NADPH oxidase is an important source of superoxide in the brain. Evidence is presented here to show that ROS are in fact important signaling molecules involved in synaptic plasticity and memory formation. Moreover, evidence that the NADPH oxidase complex is a key regulator of ROS generation in synaptic plasticity and memory formation is discussed. Understanding redox signaling in the brain, including the sources and molecular targets of ROS, are important for a full understanding of the signaling pathways that underlie synaptic plasticity and memory. Knowledge of ROS function in the brain also is critical for understanding aging and neurodegenerative diseases of the brain given that several of these disorders, including Alzheimer's disease and Parkinson disease, may be exacerbated by the unregulated generation of ROS.

Alzheimer Disease↗
PubMed2002

Glutamate receptor trafficking in synaptic plasticity.

Ionotropic glutamate receptors mediate excitatory synaptic transmission at most central mammalian synapses. In addition to converting the chemical signal released from the presynaptic terminal to an electrical response in the postsynaptic neuron, these receptors are critically involved in activity-dependent, long-term changes in synaptic strength and, therefore, are central to processes thought to underlie learning and memory. Several mechanisms have been proposed to play roles in altering synaptic strength, and it is clear that there are several different forms of long-term synaptic plasticity in the mammalian brain. Here, we review recent evidence that some forms of synaptic strengthening rely on the modification of the glutamate receptor complement at synapses in response to activity-dependent processes.

Animals↗
PubMed2002

AMPA receptor trafficking and synaptic plasticity.

Activity-dependent changes in synaptic function are believed to underlie the formation of memories. Two prominent examples are long-term potentiation (LTP) and long-term depression (LTD), whose mechanisms have been the subject of considerable scrutiny over the past few decades. Here we review the growing literature that supports a critical role for AMPA receptor trafficking in LTP and LTD, focusing on the roles proposed for specific AMPA receptor subunits and their interacting proteins. While much work remains to understand the molecular basis for synaptic plasticity, recent results on AMPA receptor trafficking provide a clear conceptual framework for future studies.

Animals↗
PubMed1998

Mineralocorticoid receptor-mediated enhancement of neuronal excitability and synaptic plasticity in the dentate gyrus in vivo is dependent on the beta-adrenergic activity.

The dentate gyrus neurons in the hippocampus contain a high density of both mineralocorticoid and adrenergic receptors. By in vivo extracellular recording from adrenalectomized rats we investigated the possible relationships between the two systems with regard to neuronal excitability and activity-dependent synaptic plasticity. Pretreatment with aldosterone significantly enhanced both basal neuronal excitability and tetanically evoked synaptic plasticity in adrenalectomized, but not sham-operated rats. The enhancement was blocked by spironolactone, indicating a mineralocorticoid receptor-dependent effect. The adrenomedullary hormone epinephrine also significantly enhanced synaptic plasticity via activation of beta-adrenergic receptors. Beta-adrenergic antagonist propranolol, infused directly into the dentate gyrus granule cell layer, significantly reduced the effect of aldosterone on neuronal excitability and partly canceled the aldosterone-enhanced synaptic plasticity. No effect of propranolol was found after its amygdaloid infusion. The mineralocorticoid receptor antagonist spironolactone did not affect the epinephrine-induced effects. These results indicate that the pretreated adrenal steroids interact with the catecholaminergic system in the dentate gyrus of adrenalectomized rats and that the functional beta-adrenergic pathway is involved in the mechanism of mineralocorticoid-induced cellular effects in vivo.

Adrenalectomy↗
PubMed1997

Neurotrophic factors in brain synaptic plasticity.

Various intercellular signals influence the strength and mode of synaptic neurotransmission and contribute to synaptic plasticity. Such signals include neurotransmitters, gas molecules, and protein factors. In response to certain neural stimuli, these molecules are liberated from presynaptic and postsynaptic neurons, glial cells, and immune cells and synergistically alter synaptic neurotransmission over the long or short term. The short-term actions often involve presynaptic activities leading to long-term potentiation. However, it is now known that various protein factors including growth factors, cytokines, and neurotrophic factors can produce not only such short-term effects but also long-term synaptic modification of presynaptic and postsynaptic neurons by altering the production of neurotransmitters and the expression of their receptors or synaptic organization. The present review focuses on these intercellular protein factors and discusses the way in which they regulate synaptic plasticity.

Animals↗
PubMed2000

Natural patterns of activity and long-term synaptic plasticity.

Long-term potentiation (LTP) of synaptic transmission is traditionally elicited by massively synchronous, high-frequency inputs, which rarely occur naturally. Recent in vitro experiments have revealed that both LTP and long-term depression (LTD) can arise by appropriately pairing weak synaptic inputs with action potentials in the postsynaptic cell. This discovery has generated new insights into the conditions under which synaptic modification may occur in pyramidal neurons in vivo. First, it has been shown that the temporal order of the synaptic input and the postsynaptic spike within a narrow temporal window determines whether LTP or LTD is elicited, according to a temporally asymmetric Hebbian learning rule. Second, backpropagating action potentials are able to serve as a global signal for synaptic plasticity in a neuron compared with local associative interactions between synaptic inputs on dendrites. Third, a specific temporal pattern of activity--postsynaptic bursting--accompanies synaptic potentiation in adults.

Action Potentials↗
PubMedDate not supplied

[The general principles of synaptic plasticity in the neocortex, hippocampus and cerebellum].

The unitary model of synaptic plasticity for the neocortical, hippocampal and cerebellar Purkinje cells is proposed. The model is based on the new modification rules. It was assumed that the necessary conditions for synaptic modifications are: the coincidence of pre- and postsynaptic cells activity (Hebbian rule) and the change of pre- and/or postsynaptic cell activity during the time that is sufficient for the shift of the ratio between protein kinases and protein phosphatases in postsynaptic cell. According to the suggested model similar mechanisms underlie homo-, hetero- and associative LTP and LTD of excitatory and inhibitory synaptic transmission. The involvement of cAMP and cGMP in synaptic plasticity of neocortical/hippocampal and Purkinje cells, correspondingly, may underlie the different Ca(2+)-dependent modification rules in these structures. The model is used for the analysis of stimulation parameters influence on the direction of synaptic modification. It is shown that stimulation frequency (Ca2+ rise) necessary for LTP or LTD induction is relative but not absolute.

Animals↗
PubMed2006

Cyclin-dependent kinase 5 in synaptic plasticity, learning and memory.

Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase with a multitude of functions. Although Cdk5 is widely expressed, it has been studied most extensively in neurons. Since its initial characterization, the fundamental contribution of Cdk5 to an impressive range of neuronal processes has become clear. These phenomena include neural development, dopaminergic function and neurodegeneration. Data from different fields have recently converged to provide evidence for the participation of Cdk5 in synaptic plasticity, learning and memory. In this review, we consider recent data implicating Cdk5 in molecular and cellular mechanisms underlying synaptic plasticity. We relate these findings to its emerging role in learning and memory. Particular attention is paid to the activation of Cdk5 by p25, which enhances hippocampal synaptic plasticity and memory, and suggests formation of p25 as a physiological process regulating synaptic plasticity and memory.

Animals↗
PubMed2005

Rapid eye movement sleep deprivation revives a form of developmentally regulated synaptic plasticity in the visual cortex of post-critical period rats.

The critical period for observing a developmentally regulated form of synaptic plasticity in the visual cortex of young rats normally ends at about postnatal day 30. This developmentally regulated form of in vitro long-term potentiation (LTP) can be reliably induced in layers II-III by aiming high frequency, theta burst stimulation (TBS) at the white matter situated directly below visual cortex (LTPWM-III). Previous work has demonstrated that suppression of sensory activation of visual cortex, achieved by rearing young rats in total darkness from birth, delays termination of the critical period for inducing LTPWM-III. Subsequent data also demonstrated that when rapid eye movement sleep (REMS) is suppressed, thereby reducing REMS cortical activation, just prior to the end of the critical period, termination of this developmental phase is delayed, and LTPWM-III can still be reliably produced in the usual post-critical period. Here, we report that for approximately 3 weeks immediately following the usual end of the critical period, suppression of REMS disrupts the maturational processes that close the critical period, and LTPWM-III is readily induced in brain slices taken from these somewhat older animals. Insofar as in vitro LTP is a model for the cellular and molecular changes that underlie developmental synaptic plasticity, these results suggest that mechanisms of synaptic plasticity, which participate in brain development and perhaps also in learning and memory processes, remain susceptible to the effects of REMS deprivation during the general period of adolescence in the rat.

Animals↗
PubMed2001

Maternity leads to morphological synaptic plasticity in the oxytocin system.

The oxytocinergic system, which plays a major role in the control of different aspects of maternity, undergoes extensive synaptic and neuronal-glial remodelling during parturition and lactation and has thus become a remarkable example of activity-dependent morphological synaptic plasticity in the adult mammalian brain. The use of different comparative ultrastructural analyses on the rat supraoptic and paraventricular nuclei, together with identification of pre- and post-synaptic elements, has allowed us to show that there is a significant increase in the number of GABAergic, glutamatergic and noradrenergic synapses impinging on oxytocin neurons, concomitant with a reduction of glial coverage of the neurons. This synaptic plasticity involves axo-dendritic and axo-somatic contacts originating from terminals making one or several synaptic contacts in one plane of section. While noradrenergic afferents arise from medullary catecholaminergic neurons, our recent in vitro observations indicate that GABAergic and glutamatergic afferents derive, at least partly, from local intrahypothalamic neurons, in close proximity to oxytocin neurons. The cellular mechanisms underlying this morphological synaptic plasticity remain to be determined but it is highly likely that they depend on increased activity in both pre- and post-synaptic elements. Moreover, the oxytocin system continues to express 'embryonic' molecular features that may allow the morphological plasticity to occur. In particular, it expresses high levels of cell surface adhesion molecules currently thought to intervene in synaptic remodelling in the developing and lesioned central nervous system, including the weakly adhesive polysialylated isoform of the Neural Cell Adhesion Molecule, the axonal glycoprotein F3 and its ligand, the extracellular matrix glycoprotein, tenascin-C.

Afferent Pathways↗
PubMed2005

Effect of ganglioside on synaptic plasticity of hippocampus in lead-exposed rats in vivo.

Synaptic plasticity, including long-term potentiation (LTP), long-term depression (LTD) and depotentiation (DP), is important for learning and memory. Previous studies proved that chronic lead exposure especially during early post-natal development induced impairment on synapse plasticity. The purpose of this study is to evaluate the effect of ganglioside on the lead-induced impairments of LTP and DP in rat dentate gyrus in vivo. The experiments were carried out in three groups of rats (control, lead-exposed, ganglioside-treated lead-exposed, respectively). The input-output (I/O) function, pair pulses reaction, excitatory post-synaptic potential (EPSP) and population spike (PS) amplitude were measured in the dentate gyrus (DG) of adult rats (70-90 days) in response to stimulation applied to the lateral perforant path. The results show that (1) chronic lead exposure impaired LTP/DP measured on both EPSP slope and PS amplitude in DG area of the hippocampus. (2) The amplitudes of LTP/DP of lead-exposed group were significantly increased by supplying ganglioside. These results suggest intraperitoneally injection with ganglioside could reverse the lead-induced impairments of synaptic plasticity in rats and might be effective in attenuating the cognitive deficits induced by lead.

Animals↗
PubMedDate not supplied

Synaptic plasticity in the hippocampus during afferent activation reproducing the pattern of the theta rhythm (theta plasticity).

This review summarizes data on the plasticity of hippocampal synaptic pathways in conditions of afferent activation modeling the electrical activity of neurons during the theta rhythm. Activation with short trains of stimuli with frequencies of about 5 Hz efficiently induces long-term potentiation, i.e., stable facilitation of synaptic transmission. Contrarily, single stimuli presented at the same frequency "depotentiate" synapses or even induce long-term depression. Combined theta activity at two synaptic inputs, in phase with each other, induces long-term potentiation, while combined activity in antiphase produces long-term depression of the weakly-activated input (associative long-term potentiation and depression). Short trains of single stimuli at a frequency of 5 Hz induce heterosynaptic short-term depression: the efficiency of all synaptic inputs is decreased for time periods of the order of 1 min. Apart from changes in synaptic efficiency, theta activation affects the ability to induce synaptic rearrangements in conditions of subsequent afferent activation ("cryptic" plasticity). Thus, virtually all known types of synaptic plasticity are efficiently induced by afferent activation of the pattern of the hippocampal theta rhythm, which suggests the possible mechanisms for its roles in learning and memory processes.

Animals↗
PubMed1998

Glucocorticoid receptor and protein/RNA synthesis-dependent mechanisms underlie the control of synaptic plasticity by stress.

Learning and memory are exquisitely sensitive to behavioral stress, but the underlying mechanisms are still poorly understood. Because activity-dependent persistent changes in synaptic strength are believed to mediate memory processes in brain areas such as the hippocampus we have examined the means by which stress affects synaptic plasticity in the CA1 region of the hippocampus of anesthetized rats. Inescapable behavioral stress (placement on an elevated platform for 30 min) switched the direction of plasticity, favoring low frequency stimulation-induced decreases in synaptic transmission (long-term depression, LTD), and opposing the induction of long-term potentiation by high frequency stimulation. We have discovered that glucocorticoid receptor activation mediates these effects of stress on LTD and long-term potentiation in a protein synthesis-dependent manner because they were prevented by the glucocorticoid receptor antagonist RU 38486 and the protein synthesis inhibitor emetine. Consistent with this, the ability of exogenously applied corticosterone in non-stressed rats to mimic the effects of stress on synaptic plasticity was also blocked by these agents. The enablement of low frequency stimulation-induced LTD by both stress and exogenous corticosterone was also blocked by the transcription inhibitor actinomycin D. Thus, naturally occurring synaptic plasticity is liable to be reversed in stressful situations via glucocorticoid receptor activation and mechanisms dependent on the synthesis of new protein and RNA. This indicates that the modulation of hippocampus-mediated learning by acute inescapable stress requires glucocorticoid receptor-dependent initiation of transcription and translation.

Animals↗