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At least 721 records · Page 40Linked to original sources
PubMed2003

Active dendrites, potassium channels and synaptic plasticity.

The dendrites of CA1 pyramidal neurons in the hippocampus express numerous types of voltage-gated ion channel, but the distributions or densities of many of these channels are very non-uniform. Sodium channels in the dendrites are responsible for action potential (AP) propagation from the axon into the dendrites (back-propagation); calcium channels are responsible for local changes in dendritic calcium concentrations following back-propagating APs and synaptic potentials; and potassium channels help regulate overall dendritic excitability. Several lines of evidence are presented here to suggest that back-propagating APs, when coincident with excitatory synaptic input, can lead to the induction of either long-term depression (LTD) or long-term potentiation (LTP). The induction of LTD or LTP is correlated with the magnitude of the rise in intracellular calcium. When brief bursts of synaptic potentials are paired with postsynaptic APs in a theta-burst pairing paradigm, the induction of LTP is dependent on the invasion of the AP into the dendritic tree. The amplitude of the AP in the dendrites is dependent, in part, on the activity of a transient, A-type potassium channel that is expressed at high density in the dendrites and correlates with the induction of the LTP. Furthermore, during the expression phase of the LTP, there are local changes in dendritic excitability that may result from modulation of the functioning of this transient potassium channel. The results support the view that the active properties of dendrites play important roles in synaptic integration and synaptic plasticity of these neurons.

Animals↗
PubMed2003

Two distinct types of corticothalamic EPSPs and their contribution to short-term synaptic plasticity.

The lateral posterior nucleus (LPN) is innervated by two different morphological types of cortical terminals that originate from cortical layers V and VI. Here we describe two distinct types of excitatory postsynaptic potentials (EPSPs) that were recorded in the LPN after stimulation of corticothalamic fibers. These types of EPSPs differed in amplitude, latency, rise time, and response to increasing levels of stimulus intensity. The most frequently encountered EPSP, type I, displayed a longer latency and slower rise time than the less frequently encountered type II EPSP. Type I EPSPs also showed a graded increase in amplitude with increasing levels of stimulation, whereas type II EPSPs showed an all-or-none response. In response to repetitive stimulation (0.5-20 Hz), type I EPSPs displayed frequency-dependent facilitation, whereas type II EPSPs displayed frequency-dependent depression. Further details of these distinct forms of short-term synaptic plasticity were explored using paired-pulse stimuli. Pharmacology experiments revealed that both N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors are involved in corticothalamic synaptic transmission in the LPN and contribute to both synaptic facilitation and depression. Taken together with the results of our previous anatomical studies, these results suggest that type I EPSPs arise from stimulation of layer VI afferents, whereas type II EPSPs arise from stimulation of layer V inputs. Moreover, type I and II EPSPs in the LPN may be functionally similar to corticogeniculate and retinogeniculate EPSPs, respectively.

Animals↗
PubMed2006

Arc/Arg3.1: linking gene expression to synaptic plasticity and memory.

Arc/Arg3.1 is an effector immediate-early gene implicated in the consolidation of memories. Although cloned a decade ago, the physiological role of Arc/Arg3.1 in the brain has remained elusive. Four papers in this issue of Neuron address this function. These studies show that Arc/Arg3.1 regulates endophilin 3 and dynamin 2, two components of the endocytosis machinery. Genetic ablation of Arc/Arg3.1 in mice or overexpression in culture suggest that Arc/Arg3.1 regulates AMPA receptor trafficking and synaptic plasticity. Finally, Arc/Arg3.1 knockout mice show memory retention deficits. These recent developments provide new insights into the function of this popular activity-dependent neuronal marker.

Animals↗
PubMed2006

Secretin receptor-deficient mice exhibit impaired synaptic plasticity and social behavior.

Secretin is a peptide hormone released from the duodenum to stimulate the secretion of digestive juice by the pancreas. Secretin also functions as a neuropeptide hormone in the brain, and exogenous administration has been reported to alleviate symptoms in some patients with autism. We have generated secretin receptor-deficient mice to explore the relationship between secretin signaling in the brain and behavioral phenotypes. Secretin receptor-deficient mice are overtly normal and fertile; however, synaptic plasticity in the hippocampus is impaired and there are slightly fewer dendritic spines in the CA1 hippocampal pyramidal cells. Furthermore, secretin receptor-deficient mice show abnormal social and cognitive behaviors. These findings suggest that the secretin receptor system has an important role in the central nervous system relating to social behavior.

Animals↗
PubMed2025

Neuropeptide-mediated synaptic plasticity regulates context-dependent mating behaviors in Drosophila.

Neuropeptides play crucial roles in regulating context-dependent behaviors, but the underlying mechanisms remain elusive. We investigate the role of the neuropeptide SIFa and its receptor SIFaR in regulating two distinct mating duration behaviors in male Drosophila: Longer-Mating-Duration (LMD) and Shorter-Mating-Duration (SMD). We found that SIFaR expression in specific neurons is required for both LMD and SMD behaviors. Social context and sexual experience lead to synaptic reorganization between SIFa and SIFaR neurons, altering internal states of brain. We revealed that the SIFa-SIFaR/Crz-CrzR neuropeptide relay pathway is essential for generating distinct interval timing behaviors, with Crz neurons being responsive to the activity of SIFa neurons. Additionally, CrzR expression in glial cell population is critical for regulating LMD behavior. Our study provides insights into how neuropeptides and their receptors modulate context-dependent behaviors through synaptic plasticity and calcium signaling, with implications for understanding the neural circuitry underlying interval timing and neuropeptidergic system modulation of behavioral adaptations.

Animals↗
PubMed2005

Role of hippocampal Cav1.2 Ca2+ channels in NMDA receptor-independent synaptic plasticity and spatial memory.

Current knowledge about the molecular mechanisms of NMDA receptor (NMDAR)-independent long-term potentiation (LTP) in the hippocampus and its function for memory formation in the behaving animal is limited. NMDAR-independent LTP in the CA1 region is thought to require activity of postsynaptic L-type voltage-dependent Ca2+ channels (Cav1.x), but the underlying channel isoform remains unknown. We evaluated the function of the Cav1.2 L-type Ca2+ channel for spatial learning, synaptic plasticity, and triggering of learning-associated biochemical processes using a mouse line with an inactivation of the CACNA1C (Cav1.2) gene in the hippocampus and neocortex (Cav1.2(HCKO)). This model shows (1) a selective loss of protein synthesis-dependent NMDAR-independent Schaffer collateral/CA1 late-phase LTP (L-LTP), (2) a severe impairment of hippocampus-dependent spatial memory, and (3) decreased activation of the mitogen-activated protein kinase (MAPK) pathway and reduced cAMP response element (CRE)-dependent transcription in CA1 pyramidal neurons. Our results provide strong evidence for a role of L-type Ca2+ channel-dependent, NMDAR-independent hippocampal L-LTP in the formation of spatial memory in the behaving animal and for a function of the MAPK/CREB (CRE-binding protein) signaling cascade in linking Cav1.2 channel-mediated Ca2+ influx to either process.

2-Amino-5-phosphonovalerate↗
PubMed2000

Substantia nigra dopamine regulates synaptic plasticity and membrane potential fluctuations in the rat neostriatum, in vivo.

The spiny projection neurons of the neostriatum are a site at which dopamine inputs from the substantia nigra converge with excitatory inputs from the cerebral cortex. These two systems interact in certain learning and motor control mechanisms of the brain. We investigated these interactions using intracellular recording from spiny striatal neurons in urethane-anaesthetized rats. We found that acute dopamine depletion was associated with long-term depression of corticostriatal synaptic input. Electrical stimulation of the cortex which mimicked synchronous cortical input to striatal neurons also induced long-term depression of corticostriatal inputs. In intact control animals, but not in dopamine-depleted animals, this depression was prevented or reversed by concomitant stimulation of the substantia nigra. In agreement with previous in vitro studies, our in vivo findings show that long-term depression occurs in the corticostriatal pathway, and in addition show that it is regulated by dopaminergic inputs from the substantia nigra. This form of synaptic plasticity may therefore be important for understanding disturbances of the motor system seen in humans with Parkinson's disease.

Animals↗
PubMed1994

Gonadal hormones as promoters of structural synaptic plasticity: cellular mechanisms.

It is now obvious that the CNS is capable of undergoing a variety of plastic changes at all stages of development. Although the magnitude and distribution of these changes may be more dramatic in the immature animal, the adult brain retains a remarkable capacity for undergoing morphological and functional modifications. Throughout development, as well as in the postpubertal animal, gonadal steroids exert an important influence over the architecture of specific sex steroid-responsive areas, resulting in sexual dimorphisms at both morphological and physiological levels. We are only now beginning to gain insight into the mechanisms involved in gonadal steroid-induced synaptic changes. The number of synaptic inputs to specific neuronal populations is sexually dimorphic and this can be modulated by changes in the sex steroid environment. These modifications can be correlated with other morphological changes, such as glial cell activation, that are occurring simultaneously in the same anatomical area. Indeed, the close physical relationship between glial cells and neuronal synaptic contacts makes them an ideal candidate for participating in this process. Interestingly, not only can the morphology and immunoreactivity of glial cells be modulated by gonadal steroids, but a close negative correlation between the number of synapses and the amount of glial ensheathing of a neuron has been demonstrated, suggesting an active participation of these cells in this process. Glia have sex steroid receptors, are capable of producing and metabolizing steroids, and can produce other neuronal trophic factors in response to sex steroids. Hence, their role in gonadal steroid-induced synaptic plasticity is becoming more apparent. In addition, there is recent evidence that this process may involve certain cell surface molecules, such as the N-CAMs, since a specific isoform of this molecule, previously referred to as the embryonic form, is found in those areas of the brain which maintain the capacity to undergo synaptic remodelling. However, there is much work to be done in order to fully understand this phenomenon and before bringing it into a clinical setting in hopes of treating neurodegenerative diseases or injuries to the nervous system.

Androgens↗
PubMed2006

Effects of secreted oligomers of amyloid beta-protein on hippocampal synaptic plasticity: a potent role for trimers.

The accumulation of amyloid beta-protein (Abeta) in brain regions serving memory and cognition is a central pathogenic feature of Alzheimer's disease (AD). We have shown that small soluble oligomers of human Abeta that are naturally secreted by cultured cells inhibit hippocampal long-term potentiation (LTP) in vitro and in vivo and transiently impair the recall of a complex learned behaviour in rats. These results support the hypothesis that diffusible oligomers of Abeta initiate a synaptic dysfunction that may be an early event in AD. We now report detailed electrophysiological analyses that define conditions under which acute application of soluble Abeta inhibits hippocampal synaptic plasticity in wild-type mice. To ascertain which Abeta assemblies contribute to the impairment of LTP, we fractionated oligomers by size-exclusion chromatography and found that Abeta trimers fully inhibit LTP, whereas dimers and tetramers have an intermediate potency. Natural Abeta oligomers are sensitive to heat denaturation, primarily inhibit the induction phase of LTP, and cause a sustained impairment of LTP even after extensive washout. We observed no effects of Abeta oligomers on presynaptic vesicle release. LTP in juvenile mice is resistant to the effects of Abeta oligomers, as is brain-derived-neurotrophic-factor-induced LTP in adult hippocampus. We conclude that specific assemblies, particularly timers, of naturally secreted Abeta oligomers are potent and selective inhibitors of certain forms of hippocampal LTP.

Amyloid beta-Peptides↗
PubMed2004

Afferent input modulates neurotrophins and synaptic plasticity in the spinal cord.

The effects of eliminating or decreasing neuromuscular activity on the expression of neurotrophins and associated molecules in the spinal cord and subsequent effects on spinal cord plasticity were determined. Spinal cord isolation (SI), which eliminates any supraspinal and peripheral monosynaptic input to the lumbar region but maintains the motoneuron-muscle connectivity, decreased the levels of brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) mRNA and protein in the isolated segments. Synapsin I, an important mediator for the effects of BDNF on synaptic plasticity, also was lower in the lumbar region of SI rats. In contrast, the levels of BDNF, synapsin, and growth-associated protein (GAP-43) were increased in the cervical spinal cord enlargement rostral to the isolated region, most likely reflecting an increased use of the forelimbs in the SI rats. GAP-43 levels were also increased in the lumbar spinal cord region, probably associated with compensatory mechanisms related to the deafferentation. In a separate set of experiments, the soleus muscle was paralyzed unilaterally via intramuscular botulinum toxin type A (BTX-A) injection to determine the effects of reducing the propioceptive input, of this normally highly active muscle on neurotrophin expression in the spinal cord. BDNF and synapsin I mRNAs were lower and NT-3 levels were higher in the lumbar hemicord ipsilateral to the BTX-A injection. Combined, these results indicate that the level of supraspinal and muscle afferent input plays an important role in modulating the levels of BDNF and NT-3 in the spinal cord.

Animals↗
PubMed1994

Motor deficit and impairment of synaptic plasticity in mice lacking mGluR1.

Metabotropic glutamate receptor 1 (mGluR1) is a member of a large family of G-protein-coupled glutamate receptors, the physiological functions of which are largely unknown. Mice deficient in mGluR1 have severe motor coordination and spatial learning deficits. They have no gross anatomical or basic electrophysiological abnormalities in either the cerebellum or hippocampus, but they show impaired cerebellar long-term depression and hippocampal mossy fibre long-term potentiation. mGluR1-deficient mice should therefore be valuable models for studying synaptic plasticity.

Animals↗
PubMed2006

Age-dependent glutamate induction of synaptic plasticity in cultured hippocampal neurons.

A common denominator for the induction of morphological and functional plasticity in cultured hippocampal neurons involves the activation of excitatory synapses. We now demonstrate massive morphological plasticity in mature cultured hippocampal neurons caused by a brief exposure to glutamate. This plasticity involves a slow, 70%-80% increase in spine cross-section area associated with a significant reduction in the width of dendrites. These changes are age dependent and expressed only in cells >18 d in vitro (DIV). Activation of both NMDARs and AMPARs as well as a sustained rise of internal calcium levels are necessary for induction of this plasticity. On the other hand, blockade of network activity or mGluRs does not abolish the observed morphological plasticity. Electrophysiologically, a brief exposure to glutamate induces an increase in the magnitude of EPSCs evoked between pairs of neurons, as well as in mEPSC frequency and amplitude, in mature but not young cultures. These results demonstrate an age-dependent, rapid and robust morphological and functional change in cultured central neurons that may contribute to their ability to express long term synaptic plasticity.

Adaptation, Physiological↗
PubMed2003

Regulation of AMPA receptor activity, synaptic targeting and recycling: role in synaptic plasticity.

The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors for the neurotransmitter glutamate are oligomeric structures responsible for most fast excitatory responses in the central nervous system. The activity of AMPA receptors can be directly regulated by protein phosphorylation, which may also affect the interaction with intracellular proteins and, consequently, their recycling and localization to defined postsynaptic sites. This review focuses on recent advances in understanding the dynamic regulation of AMPA receptors, on a short- and long-term basis, and its implications in synaptic plasticity.

Animals↗
PubMedDate not supplied

[Interactions between the hippocampus and the amygdala in synaptic plasticity processes. A key to understanding the relations between motivation and memory].

INTRODUCTION: Memory is initially stored as a transitory change that can become consolidated and converted into a long term memory trace. Consolidation largely depends on the emotional state. It is known that the hippocampus plays a role in the consolidation process of certain types of memory and that the amygdala might modulate the consolidation of the memory traces in other parts of the brain. The interaction between these two structures is crucial in many forms of learning and memory. METHOD: The hippocampus, as well as the amygdala, display a type of synaptic plasticity known as long term potentiation (LTP), which is considered to be a cellular memory mechanism. Recently, it has been reported that the consolidation of the hippocampal LTP may be modulated, like memory, by the emotional state and by the activation of the basolateral amygdala. These findings, taken as a whole, can help to explain how the processes of consolidation of memory take place. At the same time they also constitute a more physiological model of the learning and memory processes, which will provide us with a more accurate understanding of the mechanisms behind the consolidation of the memory.

Amygdala↗
PubMed1997

Lamotrigine inhibits tetraethylammonium-induced synaptic plasticity in the rat amygdala.

Although long-term potentiation was generally initiated by a brief tetanus, in the hippocampus, it could also be evoked by application of the K+ channel blocker tetraethylammonium. The present study was aimed at investigating the effect of lamotrigine, a new anticonvulsant, on the tetraethylammonium-induced potentiation in brain slices of the rat amygdala using intracellular recording techniques. Bath application of tetraethylammonium (20 mM) for 10 min resulted in a long-lasting enhancement of the amplitude of excitatory postsynaptic potentials to 235 +/- 12% of control (n = 6, P < 0.001). Pretreatment of the slices with nifedipine (10 microM) abolished the potentiation, suggesting that tetraethylammonium long-term potentiation in the amygdala is due to Ca2+ influx through voltage-dependent Ca2+ channels. By contrast, N-methyl-D-aspartate receptor activation was not required because D-2-amino-5-phosphonovalerate (50 microM) did not prevent the tetraehylammonium long-term potentiation. Superfusion of lamotrigine (50 microM) depressed the excitatory postsynaptic potential to 53.8 +/- 3.9% of control. Tetraethylammonium was subsequently added in the presence of lamotrigine but failed to enhance the excitatory postsynaptic potential. Bursts of Ca2+ spikes evoked by a depolarizing pulse or by synaptic stimulation under tetraethylammonium were depressed by lamotrigine. It is concluded that lamotrigine is capable of inhibiting tetraethylammonium-induced synaptic plasticity. The underlying mechanism is likely due to lamotrigine's inhibition of postsynaptic voltage-dependent Ca2+ channels. Considering that tetraethylammonium is a convulsant agent and brief seizure episodes induced long-term potentiation, fibre sprouting and the development of aberrant synaptic contacts, lamotrigine could be a potential neuroprotective agent, especially in pathological situations where excessive glutamate release occurs.

Amygdala↗
PubMed1982

Cytoplasmic actin in neuronal processes as a possible mediator of synaptic plasticity.

We have demonstrated that, after permeation with saponin and decoration with S-1 myosin subfragment, the cytoplasmic actin is organized in filaments in dendritic spines, dendrites, and axon terminals of the dentate molecular layer. The filaments are associated with the plasma membrane and the postsynaptic density with their barbed ends and also in parallel with periodical cross bridges. In the spine stalks and dendrites, the actin filaments are organized in long strands. Given the contractile properties of actin, these results suggest that the cytoplasmic actin may be involved in various forms of experimentally induced synaptic plasticity by changing the shape or volume of the pre- and postsynaptic side and by retracting and sprouting synapses.

Actins↗
PubMed2005

Cortistatin overexpression in transgenic mice produces deficits in synaptic plasticity and learning.

Cortistatin-14 (CST) is a neuropeptide expressed in cortical and hippocampal interneurons that shares 11 of 14 residues with somatostatin. In contrast to somatostatin, infusion of CST decreases locomotor activity and selectively enhances slow wave sleep. Here, we show that transgenic mice that overexpress cortistatin under the control of neuron-specific enolase promoter do not express long-term potentiation in the dentate gyrus. This blockade of dentate LTP correlates with profound impairment of hippocampal-dependent spatial learning. Exogenously applied CST to slices of wild-type mice also blocked induction of LTP in the dentate gyrus. Our findings implicate cortistatin in the modulation of synaptic plasticity and cognitive function. Thus, increases in hippocampal cortistatin expression during aging could have an impact on age-related cognitive deficits.

Aging↗
PubMed2004

Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo.

We have previously shown that voluntary exercise produces enhanced neurogenesis and long-term potentiation (LTP) in the dentate gyrus (DG) of mice in vitro. In the present experiments we show that rats given access to a running wheel (Runners) exhibit significantly more short-term potentiation and LTP with theta-patterned conditioning stimulation in vivo than do age-matched litter mates (Controls). This increase in LTP appears to reflect an alteration in the induction threshold for synaptic plasticity that accompanies voluntary exercise. Weak theta-patterned stimulation, which did not produce LTP in control subjects, produced a robust and long-lasting LTP in Runners. LTP induction in both groups was dependent upon the activation of N-methyl-D-aspartate (NMDA) receptors, and could be blocked by the competitive antagonist [+/-]-3-[2-carboxypiperazin-4-yl] propanephosphonic acid. Consistent with these findings, we found that mRNA levels for NR2B subtype of NMDA receptor were increased specifically in the DG of Runners. In addition to changes in NR2B mRNA levels, quantitative polymerase chain reaction analysis revealed that brain-derived neurotrophic factor (BDNF) and glutamate receptor 5 mRNA levels were also significantly elevated in the DG of Runners, but not in other areas of the hippocampus. Thus, alterations in the expression of BDNF, and specific glutamate receptor subtypes, may underlie the ability of exercise to enhance neurogenesis and reduce the threshold for LTP in the DG.

Age Factors↗