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Results for “synaptic plasticity”

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At least 973 records · Page 54Linked to original sources
PubMed2006

Dendritic calcium spikes induce bi-directional synaptic plasticity in the lateral amygdala.

Postsynaptic induction of long-term potentiation (LTP) at cortical and thalamic afferent synapses onto lateral amygdala (LA) projection neurons not only involves NMDA receptor activation, but also depends on L-type voltage-dependent calcium channels (L-VDCCs). Here we show, using whole cell recordings and two-photon Ca2+ imaging, that L-VDCCs contribute to the induction of dendritic Ca2+ spikes in LA projection neurons. Dendritic Ca2+ spikes can be induced in the absence of sodium spikes by supra-threshold somatic depolarization or by pairing sub-threshold depolarization with synaptic stimulation. Moreover, synaptic induction of Ca2+ spikes is facilitated by R-VDCCs in a pathway-specific manner. Once induced, dendritic Ca2+ spikes propagate into large parts of the dendritic tree. We show that pairing synaptic stimulation with single dendritic Ca2+ spikes can induce bi-directional plasticity, the sign of which might be determined by the anatomical location of active synaptic inputs relative to the spike initiation zone. These data suggest an important role for dendritic Ca2+ spikes in dendritic integration and provide a mechanism by which local synaptic activity may influence global dendritic integration in LA projection neurons.

Action Potentials↗
PubMed2002

Postsynaptic kinase signaling underlies inhibitory synaptic plasticity in the lateral superior olive.

UNLABELLED: In the auditory system, inhibitory transmission from the medial nucleus of the trapezoid body (MNTB) to neurons of the lateral superior olivary nucleus (LSO) undergoes activity-dependent long-term depression, and may be associated with developmental elimination of these synapses [Sanes DH, Friauf E (2000). REVIEW: development and influence of inhibition in the laterial superior olivary nucleus. Hear Res 147:46-58]. Although GABA(B) receptor activation and postsynaptic free calcium are implicated in this depression, little is known about intracellular signaling mechanisms in this or other forms of inhibitory plasticity. In this study, we asked whether the calcium dependency of inhibitory depression was associated with the activation of calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase C (PKC), and/or cAMP-dependent protein kinase A (PKA). Whole-cell voltage-clamp recordings were obtained from LSO neurons in a brain slice preparation, permitting for the selective pharmacologic manipulation of individual postsynaptic LSO neurons. Inclusion of a CaMKII antagonist (KN-62) in the internal pipet solution blocked inhibitory synaptic depression. A second CaMKII inhibitor (autocamtide peptide fragment) significantly decreased inhibitory depression. Inclusion of a specific antagonist of protein kinase C (PKC fragment 19-36) in the internal recording solution also blocked inhibitory depression. To test involvement of a cAMP-dependent intracellular cascade, two different manipulations were performed. Inclusion of PKA antagonists (Rp-cAMPS or a cAMP dependent protein kinase inhibitor peptide) prevented inhibitory depression. In contrast, when a nonhydrolyzable cAMP analog (Sp-cAMPS) was permitted to enter the postsynaptic cell, the MNTB-evoked IPSCs became depressed in the absence of low-frequency stimulation. Thus, three key postsynaptic kinases, CaMKII, PKC, and PKA, participate in the activity-dependent depression of inhibitory MNTB-LSO synapses during postnatal development.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2002

Stress, synaptic plasticity, and psychopathology.

It is now generally recognized that stressful events play a critical role in the genesis of psychopathology. The neurobiological mechanisms that mediate the contribution of stressful events to the manifestation of psychiatric disorders may include changes in synaptic efficacy in different brain areas. Numerous studies in animals have begun to identify some of these areas through experiments manipulating stressful components. This review focuses on alterations of synaptic efficacy in the hippocampus, the lateral septum, and the medial prefrontal cortex that mimic the pathophysiology of depression and post-traumatic stress disorder.

Animals↗
PubMed2005

Timing in synaptic plasticity: from detection to integration.

Timing of cellular and subcellular events contributes to spiking-induced modification of synapses in a variety of ways. Initially, the timing of presynaptic and postsynaptic action potentials must be translated into signals that can initiate intracellular processes. Recent experimental and computational findings suggest that the spatiotemporal details of such signals, in particular the time courses and locations of postsynaptic Ca(2+) transients, might themselves be crucial for driving potentiation and depression modules that interact in a time-dependent way to determine plasticity outcomes. On longer timescales, the effects of multiple spikes are integrated in a nonlinear manner, yielding non-intuitive plasticity results that are likely to be sensitive to local conditions and, finally, additional elements must be called into action to stabilize changes in synaptic strengths. This review is part of the TINS Synaptic Connectivity series.

Action Potentials↗
PubMed2002

Synaptic plasticity in the acoustic startle pathway: the neuronal basis for short-term habituation?

The aim of the present study was to analyse the cellular mechanism underlying short-term habituation of the acoustic startle response (ASR). We explored distinct synapses of the neuronal startle pathway in rat brain slices by patch-clamp recordings of giant neurons in the caudal pontine reticular formation. Presynaptic stimulation of auditory afferents by repeated bursts at 0.1 and 1 Hz led to an exponential decay of EPSC magnitudes. This homosynaptic depression (HSD) was reversible and repeatedly inducible after recovery. Many parameters of HSD in vitro match those of ASR habituation in vivo. The mechanisms underlying HSD are distinct from classical short-term plasticity: paired-pulse as well as paired-burst stimulation revealed a facilitation of the second EPSC, occurring in a much smaller time window up to interstimulus intervals of 200 ms. Pharmacological experiments demonstrated that HSD could be completely blocked by the group II and III metabotropic glutamate receptor antagonist MPPG. Similar results were obtained by CPPG, another group II and III antagonist. In contrast, HSD was not affected by the group I and II antagonist MCPG. We conclude that we found a form of synaptic depression in synapses within the primary startle pathway which correlates in many respects with short-term habituation of the ASR and which is presumably mediated by group III metabotropic glutamate receptors.

Acoustic Stimulation↗
PubMedDate not supplied

[The influence of neuromodulators on the synaptic plasticity in dopaminergic structures of the midbrain (hypothetical mechanism)].

A mechanism underlying the effects of neuromodulators on long-term changes in the efficacy of excitatory and inhibitory inputs to dopaminergic and inhibitory cells of the substantia nigra and ventral tegmental area is suggested. According to this mechanism, activation of Gi/0 protein-coupled dopamine D2 autoreceptors and opioid kappa (mu) receptors on dopaminergic (inhibitory) cells promotes the LTD of excitatory inputs to these cells and decrease in their activity. Activation of Gq/11 protein-coupled alpha1 adrenoreceptors, muscarinic M1, neurokinin NK3 (alpha1, M3, NK1, serotonin 5-HT2) receptors on dopaminergic (inhibitory) cells as well as activation of Gs protein-coupled D1 receptors on inhibitory cells promotes the LTP of excitatory inputs to these cells and increase in their activity. Augmenting (lowering) GABA release can be provided by activation of presynaptic D1 and M3 receptors (mu, 5-HT1, and adenosine A1) receptors. Increase (decrease) in GABA concentration due to modulation of inhibitory cell activity and/or GABA release will promote the induction of LTD (LTP) of excitatory inputs to target dopamine cells. The model agree with known experimental data describing the involvement of neuromodulators in modification of dopamine cell activity and dopamine release. The suggested model can be useful in understanding the operation of neuronal networks, which include the basal ganglia.

Autoreceptors↗
PubMed1997

Synaptic plasticity: neighborhood influences.

Recent studies indicate that, when the strengths of specific synapses are modified by activity, changes in strengths also occur at neighboring synapses; this neighborhood influence has important implications for how synaptic modifications implement learning and memory.

Animals↗
PubMed1992

Modulation of an NCAM-related adhesion molecule with long-term synaptic plasticity in Aplysia.

A form of learning in the marine mollusk Aplysia, long-term sensitization of the gill- and siphon-withdrawal reflex, results in the formation of new synaptic connections between the presynaptic siphon sensory neurons and their target cells. These structural changes can be mimicked, when the cells are maintained in culture, by application of serotonin, an endogenous facilitating neurotransmitter in Aplysia. A group of cell surface proteins, designated Aplysia cell adhesion molecules (apCAM's) was down-regulated in the sensory neurons in response to serotonin. The deduced amino acid sequence obtained from complementary DNA clones indicated that the apCAM's are a family of proteins that seem to arise from a single gene. The apCAM's are members of the immunoglobulin class of cell adhesion molecules and resemble two neural cell adhesion molecules, NCAM and fasciclin II. In addition to regulating newly synthesized apCAM, serotonin also altered the amount of preexisting apCAM on the cell surface of the presynaptic sensory neurons. By contrast, the apCAM on the surface of the postsynaptic motor neuron was not modulated by serotonin. This rapid, transmitter-mediated down-regulation of a cell adhesion molecule in the sensory neurons may be one of the early molecular changes in long-term synaptic facilitation.

Amino Acid Sequence↗
PubMed2006

NMDA receptor-independent synaptic plasticity in the central amygdala in the rat model of neuropathic pain.

Neurons in the latero-capsular part of the central nucleus of the amygdala (CeA), a region now called the "nociceptive amygdala", receive predominantly nociceptive information from the dorsal horn through afferent pathways relayed at the nucleus parabrachialis (PB). Excitatory synaptic transmission between the PB afferents and these neurons is reported to become potentiated within a few hours of the establishment of arthritic or visceral pain, making it a possible mechanism linking chronic pain and unpleasant negative emotional experiences. However, it remains unknown whether such synaptic potentiation is consolidated or becomes adaptively extinct in the longer-lasting form of chronic pain, such as neuropathic pain, an as yet serious and frequent type of pain of important clinical concern. To address this issue, we recorded postsynaptic currents in CeA neurons evoked by PB tract stimulation in acute brain slices from young rats with neuropathic pain, as evaluated by tactile allodynic responses, following unilateral spinal nerve ligature made 1 week earlier. CeA neurons contralateral to the nerve ligation showed significantly larger-amplitude postsynaptic currents than those in the ipsilateral CeA and sham- and non-operated groups. The degree of synaptic potentiation, as compared between two sides, was positively correlated to that of tactile allodynia responses. In addition, blockade of NMDA receptors did not affect this potentiation. We conclude that potentiation of the PB-CeA synapse is consolidated in long-lasting neuropathic pain but that this potentiation results from a molecular mechanism distinct from that in arthritic and visceral pain.

Amygdala↗
PubMed1985

Protein kinase C phosphorylates a 47 Mr protein (F1) directly related to synaptic plasticity.

Ca2+-phospholipid-dependent protein kinase C, and activators of protein kinase C (phosphatidylserine, phorbol esters) stimulate the in vitro phosphorylation of a 47 kdalton phosphoprotein (protein F1) previously shown (Routtenberg, Lovinger and Steward, Behav. neural Biol., 43 (1985) 3-11) to be directly related to the plasticity of long-term potentiation. These data indicate that protein F1 serves as a protein kinase C substrate, and suggest the hypothesis that protein kinase C is involved in processes of long-term potentiation.

Animals↗
PubMed2004

'Deaf, mute and whispering' silent synapses: their role in synaptic plasticity.

Mechanisms of long-term potentiation (LTP) maintenance are discussed in the light of the phenomenon of silent synapses. Evidence that LTP is associated with the insertion of new AMPA receptors (AMPARs) in postsynaptically silent (deaf) synapses expressing only NMDA receptors (NMDARs) before LTP induction has led to the assumption that the debate on pre- versus postsynaptic locus of LTP expression has been resolved in favour of the latter. However, recent data indicate that these synapses are mainly presynaptically silent (mute or whispering), because the probability of glutamate release (P(r)) or glutamate concentration in the cleft is too low to activate AMPARs. In this case LTP could be explained by an increase in P(r) or enhanced glutamate concentration to activate low affinity AMPARs. Optical methods to probe calcium transients in dendritic spines have revealed an increase in P(r) during LTP with concomitant postsynaptic modifications. A hypothesis is considered that accounts for the differences in both the initial failure rates between AMPAR- and NMDAR-mediated responses, and the LTP-associated decrease in failures of AMPAR-mediated responses. According to this hypothesis, glutamate release is potentiated by the strong postsynaptic depolarization used to identify NMDAR-mediated responses. We suggest that the expression of LTP may depend on coordinated pre- and postsynaptic modifications whose relative contributions vary according to the initial state of the synapse, the experimental protocol and time after induction.

Animals↗
PubMedDate not supplied

Prefrontal cortex function, quasi-physiological stimuli, and synaptic plasticity.

The prelimbic area of rat medial frontal cortex may be functionally analogous to human/primate dorsolateral prefrontal cortex. This area may be involved in selective attention to the external stimuli and the coupling of the attention to a repertory of actions. It was suggested that this function may rely on a form of long-term memory [Biol. Rev. 77 (2002) 563]. Indeed, during learning of this type of behavior, a portion of prelimbic neurons persistently change their firing characteristics [Prog. Brain Res. 126 (2000) 287]. It is therefore important to study long-term potentiation (LTP) and depression (LTD) in rat prelimbic neurons. In this article, the author first briefly reviews recent findings on the prefrontal cortex function and discusses that the prefrontal cortex may be involved in long-term memory. Second, the author will show some new results which indicate that quasi-physiological patterns of stimuli mimicking prelimbic neuronal activity during behavior can induce LTP in prelimbic pyramidal neuron synapses. These results suggest that prelimbic neuronal activity during behavior may lastingly modify prelimbic synaptic efficacy.

Animals↗
PubMed1996

Extracellular ATP as a neurotransmitter: its role in synaptic plasticity in the hippocampus.

Growing evidence indicates that ATP may play a very important role in Long-Term Potentiation (LTP), a neurophysiological process that has been implicated in memory formation. LTP is an enhancement of synaptic strength induced by a specific pattern of high frequency stimulation, or by application of exogenous ATP. In the hippocampus LTP-inducing stimulation is accompanied by a massive, Ca(2+)-dependent release of ATP from presynaptic terminals. Released extracellular ATP may either interact with numerous types of ATP receptors present on the neuronal surface, or serve as a substrate for ecto-protein phosphorylation. The results of combined electrophysiological and biochemical experiments indicate that participation of extracellular ATP in the ecto-protein phosphorylation process is most likely involved in the permanent amplification of the synaptic response in the hippocampus.

Adenosine Triphosphate↗
PubMed1996

Hebb's concept of synaptic plasticity and neuronal cell assemblies.

Both in vertebrates and in invertebrates the study of processes of plasticity in nervous systems have led to consistent models of molecular mechanisms for the so-called Hebb's synapse. Changes of synaptic efficacy will lead to changes in the properties of assemblies of nerve cells--as seen today the correlates of purport. Donald Hebb's view of the characteristics of such assemblies appears farsighted.

History, 20th Century↗
PubMed2005

Synergistic effects of the peptide fragment D-NAPVSIPQ on ethanol inhibition of synaptic plasticity and NMDA receptors in rat hippocampus.

The L1 cell adhesion molecule has been implicated in ethanol teratogenesis as well as NMDAR-dependent long-term potentiation (LTP) of synaptic transmission, a process thought to be critical for neural development. Ethanol inhibits LTP at least in part by interacting with NMDA receptors. Ethanol also inhibits L1-mediated cell adhesion in a manner that is prevented by an octapeptide, D-NAPVSIPQ (D-NAP), as well as long chain alcohols such as 1-octanol. Here we analyzed the effects of D-NAP and 1-octanol on ethanol modulation of LTP induced by theta burst stimulation in two subfields of the rat hippocampus, the dentate gyrus and area CA1. When theta burst stimulation was delivered in ethanol (50 mM), LTP was inhibited by about 50%. Surprisingly, when D-NAP (10(-7) M) and ethanol were co-applied or applied sequentially, LTP was completely absent. The effects of D-NAP were persistent, since delivery of a second theta burst stimulation following washout of D-NAP and ethanol elicited minimal plasticity. Application of D-NAP alone had no effect on LTP induction or expression. The synergistic effect of D-NAP on ethanol inhibition of LTP was concentration-dependent since D-NAP (10(-10) M) had an intermediate effect, while D-NAP (10(-13) M) had no effect on ethanol suppression of LTP. These observations were also replicated with a different ethanol antagonist, 1-octanol, in area CA1. To address the mechanisms underlying this long-lasting suppression of LTP, the sensitivity of pharmacologically isolated NMDAR extracellular field potentials to combinations of D-NAP and ethanol was determined. D-NAP (10(-7)M) alone had no effect on NMDA extracellular field potentials; however, the peptide significantly increased the inhibitory action of ethanol on NMDA extracellular field potential. The findings suggest that D-NAP and 1-octanol selectively interact with NMDA receptors in an ethanol-dependent manner, further implicating the L1 cell adhesion molecule in alcohol-related brain disorders.

Animals↗