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 1,099 records · Page 61Linked to original sources
PubMed2005

Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2.

Apolipoprotein E receptor 2 (Apoer2), a member of the LDL receptor gene family, and its ligand Reelin control neuronal migration during brain development. Apoer2 is also essential for induction of long-term potentiation (LTP) in the adult brain. Here we show that Apoer2 is present in the postsynaptic densities of excitatory synapses where it forms a functional complex with NMDA receptors. Reelin signaling through Apoer2 markedly enhances LTP through a mechanism that requires the presence of amino acids encoded by an exon in the intracellular domain of Apoer2. This exon is alternatively spliced in an activity-dependent manner and is required for Reelin-induced tyrosine phosphorylation of NMDA receptor subunits. Mice constitutively lacking the exon perform poorly in learning and memory tasks. Thus, alternative splicing of Apoer2, a novel component of the NMDA receptor complex, controls the modulation of NMDA receptor activity, synaptic neurotransmission, and memory by Reelin.

Alternative Splicing↗
PubMed1998

Gamma-frequency oscillations: a neuronal population phenomenon, regulated by synaptic and intrinsic cellular processes, and inducing synaptic plasticity.

Neurons are extraordinarily complicated devices, in which physical and chemical processes are intercoupled, in spatially non-uniform manner, over distances of millimeters or more, and over time scales of < 1 msec up to the lifetime of the animal. The fact that neuronal populations generating most brain activities of interest are very large-perhaps many millions of cells-makes the task of analysis seem hopeless. Yet, during at least some population activities, neuronal networks oscillate synchronously. The emergence of such oscillations generates precise temporal relationship between neuronal inputs and outputs, thus rendering tractable the analysis of network function at a cellular level. We illustrate this idea with a review of recent data and a network model of synchronized gamma frequency (> 20 Hz) oscillations in vitro, and discuss how these and other oscillations may relate to recent data on back-propagating, action potentials, dendritic Ca2+ transients, long-term potentiation and GABAA receptor-mediated synaptic potentials.

Animals↗
PubMed2002

Interlimb reflexes and synaptic plasticity become evident months after human spinal cord injury.

Persons with long-standing injury to the cervical spinal cord resulting in complete or partial paralysis typically develop a wide spectrum of involuntary movements in muscles receiving innervation caudal to the level of injury. We have previously shown that these movements include brief and discrete contraction of muscles in the hand and forearm in response to innocuous sensory stimulation to the feet and legs, but we have been unable to replicate these interlimb reflexes in able- bodied subjects. Properties of these muscle responses indicate that the synaptic contacts between ascending sensory fibres and motor neurones of the cervical enlargement are more efficacious than normal. If these connections are present at all times, and require the more rostrally-placed spinal cord injury to allow their emergence, one might expect their appearance relatively soon following injury, as has been shown for studies of 'latent' synapses. Conversely, delayed appearance of these interlimb reflexes would suggest either the development of new synaptic connections or a profound strengthening of existing circuits in the cervical spinal cord due to a combination of afferent target loss and motor neurone denervation from motor tracts originating rostral to the injury site. In this study, we used repeated examinations of persons with acute injury to the cervical spinal cord to examine the time post-injury at which interlimb reflexes are first seen. Using tibial nerve stimulation at the knee as a screening test, a total of 24 subjects were found to develop interlimb reflexes following spinal cord injury. Latencies between stimulation and EMG were as brief as 32 ms for muscles of the forearm and 44 ms for muscles in the hand. These minimal delays all but rule out a supraspinal route for these interlimb reflexes. Interlimb reflexes first became evident no sooner than approximately 6 months following injury, and in some individuals were not seen until well over 1 year post-injury. Enhanced lower limb segmental excitability had emerged in nearly all of these subjects weeks or months prior to the first appearance of interlimb reflexes, arguing against a manifestation of traditional post-traumatic spasticity as a basis for this activity. This prolonged delay between time of injury and emergence of interlimb reflex activity lends support to the hypothesis that this activity represents an example of plasticity-and perhaps 'regenerative sprouting'-in the human spinal cord following traumatic injury.

Adolescent↗
PubMedDate not supplied

Age-dependent alterations in hippocampal synaptic plasticity: relation to memory disorders.

In this paper, we review the evidence indicating that the common disturbance in recent memory associated with aging is a consequence of functional and structural impairment in the hippocampal formation. In the Fischer 344 rat, an experimental model of the human age-related memory disorder was developed. The majority of aged rats of this strain show impaired performance in the 8-arm radial maze in a manner typical of young rats with bilateral hippocampal lesions. Aged animals also exhibit rapid decay of LTP and slower kindling of the perforant path-dentate synapse. Furthermore, quantitative morphometric analysis of the hippocampal synaptic architecture revealed that aged, memory-impaired rats had a specific loss of perforated axospinous synapses in the middle third of the dentate gyrus molecular layer; the extent of loss was directly related to the degree of memory dysfunction. Most important was the fact that the electrophysiological and morphological abnormalities did not appear in equally old animals with good memory.

Aging↗
PubMed2004

Learning mechanisms in addiction: synaptic plasticity in the ventral tegmental area as a result of exposure to drugs of abuse.

One of the central questions in neurobiology is how experience modifies neural function, and how changes in the nervous system permit an animal to adapt its behavior to a changing environment. Learning and adaptation to a host of different environmental stimuli exemplify processes we know must alter the nervous system because the behavioral output changes after experience. Alterations in behavior after exposure to addictive drugs are a striking example of chemical alterations of nervous system function producing long-lasting changes in behavior. The alterations produced in the central nervous system (CNS) by addictive drugs are of interest because of their relationship to human substance abuse but also because these CNS alterations produce dramatic, easily observed alterations in behavior in response to discrete stimuli. Considerable study has been given to behavioral and biochemical correlates of addiction over the past 50 or more years; however, our understanding of the cellular physiological responses of affected CNS neurons is in its infancy. This review focuses on alterations in cellular and synaptic physiology in the ventral tegmental area (VTA) in response to addictive drugs.

Animals↗
PubMed2000

Physiological consequences of morphologically detectable synaptic plasticity: potential uses for examining recovery following damage.

A growing literature indicates that brain structure is modified in various ways with experience. In this paper we briefly survey evidence that the brain retains the capacity to modify its organization in response to demands, including demands resulting from learning, throughout the lifetime. We attempt to address whether these experience-induced changes are accompanied by physiological changes that indicate a functional reorganization of the brain. The kinds of morphological changes that have been observed following brain injury appear to be very similar to those seen after learning. The similarity suggests that many of the basic mechanisms of synaptic change in the brain may be utilized for both functions. This suggests that we can take advantage of some of the methods used to test the changes in physiology with behavioral manipulations to examine the damaged brain. We advocate utilizing electrophysiological techniques to measure functional recovery from brain injury as these may be useful in evaluating both spontaneous recovery from damage and the therapeutic benefits of training, or other therapies.

Adaptation, Physiological↗
PubMed2003

Redistribution of syntaxin mRNA in neuronal cell bodies regulates protein expression and transport during synapse formation and long-term synaptic plasticity.

Syntaxin has an important role in regulating vesicle docking and fusion essential for neurotransmitter release. Here, we demonstrate that the distribution of syntaxin mRNA in cell bodies of sensory neurons (SNs) of Aplysia maintained in cell culture is affected by synapse formation, synapse stabilization, and long-term facilitation (LTF) produced by 5-HT. The distribution of the mRNA in turn regulates expression and axonal transport of the protein. Syntaxin mRNA and protein accumulated at the axon hillock of SNs during the initial phase of synapse formation. Significant numbers of granules containing syntaxin were detected in the SN axon. When synaptic strength was stable, both mRNA and protein were targeted away from the axon hillock, and the number of syntaxin granules in the SN axon was reduced. Dramatic increases in mRNA and protein accumulation at the axon hillock and number of syntaxin granules in the SN axon were produced when cultures with stable connections were treated with 5-HT that evoked LTF. Anisomycin (protein synthesis inhibitor) or KT5720 (protein kinase A inhibitor) blocked LTF, accumulation of syntaxin mRNA and protein at the axon hillock, and the increase in syntaxin granules in SN axons. The results indicate that without significant effects on overall mRNA expression, both target interaction and 5-HT via activation of protein kinase A pathway regulate expression of syntaxin and its packaging for transport into axons by influencing the distribution of its mRNA in the SN cell body.

Animals↗
PubMed2006

Glucocorticoid receptors and beta-adrenoceptors in basolateral amygdala modulate synaptic plasticity in hippocampal dentate gyrus, but not in area CA1.

The basolateral amygdala (BLA) is a key structure in a memory-modulatory system that regulates stress and stress hormones (glucocorticoid and noradrenaline) effects on hippocampal functioning. We have shown previously that priming the amygdala differentially affects plasticity in the hippocampal dentate gyrus (DG) and CA1, and mimicked acute stress effect on plasticity in these two subregions. In the present study, we investigated the mechanisms that mobilize the BLA to differentially alter plasticity in DG and CA1. Glucocorticoid receptors antagonist RU 38486 or beta-adrenoceptor antagonist propranolol were microinfused in the BLA, 10 min prior to BLA activation-induced modulation of long-term potentiation (LTP) in DG and CA1. The results showed that neither glucocorticoid nor noradrenergic transmissions in the BLA are necessary for LTP induction and for the impairing effect of amygdala activation on CA1 LTP. In contrast, blockade of glucocorticoid or noradrenergic transmission in BLA, increased baseline synaptic transmission in the DG, but suppressed the enhancing effect of BLA activation on DG LTP. These findings provide further evidence for a differential amygdala control of hippocampal subregions as well as for differential memory processes involving CA1 and DG. They also provide insight into how stress hormones exert their actions on the circuits involved in these processes.

Adrenergic beta-Antagonists↗
PubMed2001

An in vivo model for investigating bilateral synaptic plasticity across CA3/CA1 synapses in guinea pig dorsal hippocampus.

A method is described for concurrent investigation of long-term potentiation (LTP) in the left and right CA1 synapses in dorsal hippocampi in guinea pig in vivo. Briefly, animals are anesthetized with urethane, and small access holes are made in the skull through which electrodes are lowered to stimulate the left CA3 and record from both CA1 regions. Using this animal model, we have found that LTP is produced in both CA1 regions, following conditioning stimulation to the left CA3. However, in some animals LTP occurred in the left CA1 without concomitant synaptic potentiation in the contralateral CA1. We also observed that in some experiments synaptic potentiation in the contralateral CA1, when present, decayed to baseline levels even though LTP persisted in the ipsilateral CA1. To conclude, our data on bilateral LTP demonstrates findings that are best addressed in vivo.

Action Potentials↗
PubMed2002

How spiking neurons give rise to a temporal-feature map: from synaptic plasticity to axonal selection.

A temporal-feature map is a topographic neuronal representation of temporal attributes of phenomena or objects that occur in the outside world. We explain the evolution of such maps by means of a spike-based Hebbian learning rule in conjunction with a presynaptically unspecific contribution in that, if a synapse changes, then all other synapses connected to the same axon change by a small fraction as well. The learning equation is solved for the case of an array of Poisson neurons. We discuss the evolution of a temporal-feature map and the synchronization of the single cells' synaptic structures, in dependence upon the strength of presynaptic unspecific learning. We also give an upper bound for the magnitude of the presynaptic interaction by estimating its impact on the noise level of synaptic growth. Finally, we compare the results with those obtained from a learning equation for nonlinear neurons and show that synaptic structure formation may profit from the nonlinearity.

Journal Article↗
PubMedDate not supplied

Culture models for the study of estradiol-induced synaptic plasticity.

Estrogen, which classically affects areas of the brain related to reproduction, has also been found to affect brain regions important in learning and memory. Additionally, it has been suggested that estrogen exerts protective effects against neurodegenerative diseases such as Alzheimer's disease. Important mechanisms by which estrogen may confer protection are through the maintenance or modulation of existing synapses, or by the production of new ones. It has now been demonstrated that estrogen can increase synaptogenesis and spine production in the hippocampus, both in vivo as well as in primary hippocampal neurons in culture. The latter model system is the primary focus of this review. Synaptogenesis and spine production have been well characterized in developing and adult animals, and parallels between the synaptic morphology reflecting these processes can be readily observed in high-density primary hippocampal cultures. Moreover, in culture, estrogen induces a variety of ultrastructural modifications, many of which occur in vivo, that have been linked to various in vivo models of learning and memory. For these reasons, high-density hippocampal culture systems should be regarded as valuable tools with which to predict in vivo physiology, and may well be particularly useful for studies of the neuroprotective effects of estrogen.

Animals↗
PubMed2000

Searching for depolarization-induced genes that modulate synaptic plasticity and neurotrophin-induced genes that mediate neuronal differentiation.

We identify and characterize two classes of immediate-early genes: (i) genes, induced by depolarization in neurons, that play a role in depolarization-induced neuronal plasticity and (ii) genes, induced in neuronal precursors by neurotrophins, that play a causal role in neurotrophin-directed neuronal differentiation. We use rat PC12 pheochromocytoma cells to identify (i) genes preferentially induced by [depolarization or forskolin] versus [Nerve Growth Factor (NGF) or Epidermal Growth Factor (EGF)] and (ii) genes preferentially induced by NGF versus EGF. We describe (i) a collection of genes preferentially induced by depolarization/forskolin in PC12 cells and by kainic acid in vivo, and (ii) a collection of genes preferentially induced by NGF. The synaptotagmin IV gene encodes a synaptic vesicle protein whose level is modulated by depolarization. NGF preferentially induces the urokinase-plasminogen activator receptor in PC12 cells. Antisense oligonucleotide and anti-UPAR antibody experiments demonstrate that NGF-induced UPAR expression is required for NGF-driven PC12 cell differentiation.

Adrenal Gland Neoplasms↗
PubMed1999

Synucleins in synaptic plasticity and neurodegenerative disorders.

Synucleins are small highly conserved proteins in vertebrates, especially abundant in neurons and typically enriched at presynaptic terminals. Three genes in humans produce closely related synuclein proteins, all of which share a large amphipathic domain capable of reversible binding to lipid vesicles. Alpha synuclein has been specifically implicated in neurodegenerative disease. Two point mutations are genetically linked to familial Parkinson's disease, and alpha synuclein appears to form the major fibrillary component of Lewy bodies. Alpha synuclein also contributes to the intracellular inclusions of multiple system atrophy, and a fragment has been found in senile plaques in Alzheimer's disease. Although their normal cellular functions are unknown, several observations suggest the synucleins may serve to integrate presynaptic signaling and membrane trafficking. Alpha synuclein has been identified as a potent and selective inhibitor of phospholipase D2, which produces phosphatidic acid (to which synuclein binds) and is believed to function in the partitioning of membranes between the cell surface and intracellular stores. We outline a hypothesis whereby synuclein supports localized, experience-dependent turnover of synaptic membranes. Such a process may be important for lifelong learning and memory functions and may be especially vulnerable to disruption in aging-associated neurodegenerative diseases.

Animals↗
PubMed2006

The adult abdominal neuromuscular junction of Drosophila: a model for synaptic plasticity.

During its life cycle, Drosophila makes two sets of neuromuscular junctions (NMJs), embryonic/larval and adult, which serve distinct stage-specific functions. During metamorphosis, the larval NMJs are restructured to give rise to their adult counterparts, a process that is integrated into the overall remodeling of the nervous system. The NMJs of the prothoracic muscles and the mesothoracic dorsal longitudinal (flight) muscles have been previously described. Given the diversity and complexity of adult muscle groups, we set out to examine the less complex abdominal muscles. The large bouton sizes of these NMJs are particularly advantageous for easy visualization. Specifically, we have characterized morphological attributes of the ventral abdominal NMJ and show that an embryonic motor neuron identity gene, dHb9, is expressed at these adult junctions. We quantified bouton numbers and size and examined the localization of synaptic markers. We have also examined the formation of boutons during metamorphosis and examined the localization of presynaptic markers at these stages. To test the usefulness of the ventral abdominal NMJs as a model system, we characterized the effects of altering electrical activity and the levels of the cell adhesion molecule, FasciclinII (FasII). We show that both manipulations affect NMJ formation and that the effects are specific as they can be rescued genetically. Our results indicate that both activity and FasII affect development at the adult abdominal NMJ in ways that are distinct from their larval and adult thoracic counterparts

Abdomen↗
PubMed1999

Heterogeneity of synaptic plasticity at unitary CA3-CA1 and CA3-CA3 connections in rat hippocampal slice cultures.

Long-term potentiation (LTP) of unitary EPSPs, generated by pairs of monosynaptically connected CA3 and CA1 pyramidal cells, was compared with LTP of extracellularly evoked, multi-unitary EPSPs in rat hippocampal slice cultures. LTP was induced by repeated, synchronous pairing of low-frequency presynaptic and postsynaptic activity. Three differences were observed. First, LTP of multi-unitary EPSPs displayed two phases: transient (<5 min) and sustained. Potentiation of unitary EPSPs displayed both phases in 42% of experiments; the remainder showed sustained potentiation only. Unitary EPSPs displaying transient-sustained and only sustained potentiation could be recorded from single postsynaptic cells, indicating that excitatory synapses on a given cell are heterogeneous with respect to short-term plasticity. Second, whereas LTP of multi-unitary EPSPs never resulted in greater than twofold increases in amplitude (mean potentiation of 175% of control), maximal LTP of unitary EPSPs was as great as 13-fold (mean potentiation of 250%). Third, LTP could not be induced in 24% of unitary EPSPs. We provide here the first evidence for the coexistence of potentiatable and nonpotentiatable synapses on individual postsynaptic neurons. Thirty-seven percent of connections not displaying LTP exhibited long-term depression (LTD), suggesting that the connections were already maximally potentiated. In the remaining 63% of these pairs, neither LTP nor LTD could be induced, despite the existence of a pharmacologically identified, NMDA receptor-mediated EPSP component. In conclusion, there is considerable heterogeneity in the amplitude and time course of LTP expression at different synaptic connections. A substantial proportion of apparently nonplastic synapses probably accounts for the weaker potentiation displayed by compound EPSPs.

Animals↗
PubMed2006

Transient improvement in cognitive function and synaptic plasticity in rats following cancer chemotherapy.

BACKGROUND: Cancer chemotherapy has been associated with cognitive impairment. Several issues complicate such findings including the patients' health, use of multiple chemotherapeutic agents, and proper assessment of cognition. To control these factors, we conducted cognitive studies in female rats receiving cyclophosphamide or 5-fluorouracil (5FU). METHODS: Young (7 months) female Fischer-344 rats received five injections of cyclophosphamide (100 mg/kg), 5FU (150 mg/kg), or saline i.p. every 4 weeks for a total of 18 weeks. Aged (18 months) female Fischer-344 rats were treated with cyclophosphamide (80 mg/kg i.p.) for 16 weeks. After 8 to 10 weeks of recovery, rats were tested in two maze learning tasks, the Morris water maze and the Stone 14-unit T-maze. Neuronal synaptic function was assessed by examining long-term potentiation (LTP) in hippocampal slices obtained from young cyclophosphamide-treated rats. RESULTS: Despite the toxic effects induced by chemotherapy, cyclophosphamide- and 5FU-treated rats showed significantly better maze performance compared with controls. Following 29 to 42 weeks of recovery from chemotherapy, no significant effects were observed on maze performance. In aged rats, cyclophosphamide treatment for 14 weeks also produced toxicity, but no impairment in Stone maze learning after 16 weeks of recovery. When assessed during cyclophosphamide treatment, evidence of impaired LTP emerged; however, with 8 weeks of recovery following five cyclophosphamide treatments, we observed enhanced LTP. CONCLUSION: Despite toxicity accompanying chemotherapy, no evidence of impaired cognitive performance emerged after recovery. Indeed, following 7 to 9 weeks of recovery, we noted evidence of improved learning and LTP.

Age Factors↗
PubMedDate not supplied

Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning.

Fear conditioning is a form of associative learning in which subjects come to express defense responses to a neutral conditioned stimulus (CS) that is paired with an aversive unconditioned stimulus (US). Considerable evidence suggests that critical neural changes mediating the CS-US association occur in the lateral nucleus of the amygdala (LA). Further, recent studies show that associative long-term potentiation (LTP) occurs in pathways that transmit the CS to LA, and that drugs that interfere with this LTP also disrupt behavioral fear conditioning when infused into the LA, suggesting that associative LTP in LA might be a mechanism for storing memories of the CS-US association. Here, we develop a detailed cellular hypothesis to explain how neural responses to the CS and US in LA could induce LTP-like changes that store memories during fear conditioning. Specifically, we propose that the CS evokes EPSPs at sensory input synapses onto LA pyramidal neurons, and that the US strongly depolarizes these same LA neurons. This depolarization, in turn, causes calcium influx through NMDA receptors (NMDARs) and also causes the LA neuron to fire action potentials. The action potentials then back-propagate into the dendrites, where they collide with CS-evoked EPSPs, resulting in calcium entry through voltage-gated calcium channels (VGCCs). Although calcium entry through NMDARs is sufficient to induce synaptic changes that support short-term fear memory, calcium entry through both NMDARs and VGCCs is required to initiate the molecular processes that consolidate synaptic changes into a long-term memory.

Amygdala↗
PubMed2001

Ultrastructural evidence for presynaptic mu opioid receptor modulation of synaptic plasticity in NMDA-receptor-containing dendrites in the dentate gyrus.

Physiological studies have demonstrated that long-term potentiation (LTP) induction in N-methyl-D-aspartate (NMDA) receptor containing dentate granule cells following lateral perforant path stimulation is opioid dependent, involving mu-opioid receptors (MORs) on gamma-aminobutyric acid (GABA)-ergic neurons. To determine the cellular relationships of MORs to postsynaptic NMDA receptor-containing dendrites, immunoreactivity (-I) against MOR and the NMDA receptor subunit 1 (NMDAR1) was examined in the outer molecular layer of the dentate gyrus using electron microscopy. MOR-I was predominantly in axons and axon terminals. NMDAR1-I was almost exclusively in spiny dendrites, but was also in a few terminals. Using immunogold particles to localize precisely NMDAR1, one-third of the NMDAR1-I was detected on the dendritic plasmalemma; in dendritic spines plasmalemmal immunogold particles were near synaptic densities. Many MOR-labeled axons and terminals contacted NMDAR1-labeled dendrites. MOR-labeled terminals formed symmetric (inhibitory-type) synapses on NMDAR1-labeled dendritic shafts or nonsynaptically contacted NMDAR1-labeled shafts and spines. MOR-labeled axons often abutted NMDAR1-containing dendritic spines which received asymmetric (excitatory-type) synapses from unlabeled terminals. Occasionally, MOR-labeled terminals and dendrites were apposed to NMDAR1-containing terminals. These results provide anatomical evidence that endogenous enkephalins or exogenous opioid agonists could inhibit GABAergic terminals that modulate granule cell dendrites, thus boosting depolarizing events in granule cells and facilitating the activation of NMDA receptors located on their dendrites.

Animals↗