scholarly journals Signaling Mechanisms Mediating BDNF Modulation of Synaptic Plasticity in the Hippocampus

1999 ◽  
Vol 6 (3) ◽  
pp. 243-256 ◽  
Author(s):  
Wolfram A. Gottschalk ◽  
Hao Jiang ◽  
Nicole Tartaglia ◽  
Linyin Feng ◽  
Alexander Figurov ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Neurotrophic Factor ◽  
High Frequency ◽  
Hippocampal Slices ◽  
Close Relative ◽  
Signaling Mechanisms ◽  
Neurotrophin 3 ◽  
Neurotrophin Signaling

Although recent studies indicate that brain-derived neurotrophic factor (BDNF) plays an important role in hippocampal synaptic plasticity, the underlying signaling mechanisms remain largely unknown. Here, we have characterized the signaling events that mediate the BDNF modulation of high-frequency synaptic transmission. Mitogen-associated protein kinase (MAPK), phosphotidylinositol-3 kinase (PI3K), and phospholipase C-γ (PLC-γ) are the three signaling pathways known to mediate neurotrophin signaling in other systems. In neonatal hippocampal slices, application of BDNF rapidly activated MAPK and PI3K but not PLC-γ. BDNF greatly attenuated synaptic fatigue at CA1 synapses induced by a train of high-frequency, tetanic stimulation (HFS). Inhibition of the MAPK and PI3K, but not PLC-γ, prevented the BDNF modulation of high-frequency synaptic transmission. Neurotrophin-3 (NT-3), a close relative of BDNF, did not activate MAPK or PI3K and had no effect on synaptic fatigue in the neonatal hippocampus. Neither forskolin, which activated MAPK but not PI3 kinase, nor ciliary neurotrophic factor (CNTF), which activated PI3K but not MAPK, affected HFS-induced synaptic fatigue. Treatment of the slices with forskolin together with CNTF still had no effect on synaptic fatigue. Thus, although the activation of MAPK and PI3K is required, the two together are not sufficient to mediate the BDNF effect. Inhibition of new protein synthesis by anisomycin or cycloheximide did not prevent the BDNF effect. These data suggest that BDNF modulation of high-frequency transmission is independent of protein synthesis but requires MAPK and PI3K and yet another signaling pathway to act together in the hippocampus.

scholarly journals KCNQ/Kv7 Channel Regulation of Hippocampal Gamma-Frequency Firing in the Absence of Synaptic Transmission

2006 ◽  
Vol 95 (5) ◽  
pp. 3105-3112 ◽  
Author(s):  
S. Piccinin ◽  
A. D. Randall ◽  
J. T. Brown
Keyword(s):  
Synaptic Transmission ◽  
High Frequency ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Neuronal Firing ◽  
Population Spike ◽  
Channel Blockers ◽  
Kv7 Channels ◽  
Population Spikes ◽  
Gamma Frequency

Synchronous neuronal firing can be induced in hippocampal slices in the absence of synaptic transmission by lowering extracellular Ca2+ and raising extracellular K+. However, the ionic mechanisms underlying this nonsynaptic synchronous firing are not well understood. In this study we have investigated the role of KCNQ /Kv7 channels in regulating this form of nonsynaptic bursting activity. Incubation of rat hippocampal slices in reduced (<0.2 mM) [Ca2+]o and increased (6.3 mM) [K+]o, blocked synaptic transmission, increased neuronal firing, and led to the development of spontaneous periodic nonsynaptic epileptiform activity. This activity was recorded extracellularly as large (4.7 ± 1.9 mV) depolarizing envelopes with superimposed high-frequency synchronous population spikes. These intraburst population spikes initially occurred at a high frequency (about 120 Hz), which decayed throughout the burst stabilizing in the gamma-frequency band (30–80 Hz). Further increasing [K+]o resulted in an increase in the interburst frequency without altering the intraburst population spike frequency. Application of retigabine (10 μM), a Kv7 channel modulator, completely abolished the bursts, in an XE-991–sensitive manner. Furthermore, application of the Kv7 channel blockers, linopirdine (10 μM) or XE-991 (10 μM) alone, abolished the gamma frequency, but not the higher-frequency population spike firing observed during low Ca2+/high K+ bursts. These data suggest that Kv7 channels are likely to play a role in the regulation of synchronous population firing activity.

Medial amygdala enhances synaptic transmission and synaptic plasticity in the dentate gyrus of rats in vivo

1995 ◽  
Vol 74 (5) ◽  
pp. 2201-2203 ◽  
Author(s):  
Y. Ikegaya ◽  
K. Abe ◽  
H. Saito ◽  
N. Nishiyama
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Dentate Gyrus ◽  
High Frequency ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Medial Amygdala ◽  
Frequency Stimulation ◽  
Stimulation Of

1. The present experiment was designed to test whether synaptic transmission and synaptic plasticity in the dentate gyrus were modulated by the medial amygdala (MeA). Field potentials in the dentate gyrus (DG) evoked by stimulations of the medial perforant path (PP) were extracellularly recorded in anesthetized rats. 2. Although single-pulse stimulation of the MeA augmented PP stimulation-evoked population spike amplitude in the DG transiently, high-frequency stimulation (100 Hz for 1 s) of the MeA induced long-lasting enhancement of synaptic transmission that was not occluded by PP tetanus-induced long-term potentiation (LTP). 3. When high-frequency stimulation of the MeA was applied concurrently with weak tetanus of the PP, which alone induced only marginal LTP, the magnitude of LTP increased considerably. 4. These results demonstrate that neuron activities in the MeA induce short- and long-lasting changes in the excitability of the PP-DG synapses and thereby enhance their synaptic plasticity.

scholarly journals Enhancement of synaptic AMPA receptors depends mutually on Src and PSD-95

2020 ◽  
Author(s):  
Xiaojie Huang ◽  
Juliane M. Krüger ◽  
Anna Beroun ◽  
Weifeng Xu ◽  
Yan Dong ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Ampa Receptors ◽  
Domain Swapping ◽  
Mutual Dependence ◽  
Protein Motifs ◽  
Signaling Mechanisms ◽  
Continuous Activity ◽  
Maguk Protein

AbstractSynaptic incorporation and removal of AMPA receptors is highly regulated to modulate the strength of synaptic transmission for long-term synaptic plasticity during brain development and associative learning. PSD-93α2 and PSD-95α, two paralogs of the DLG-MAGUK protein family of signaling scaffolds govern the synaptic incorporation and stabilization of AMPA receptors opposingly, with PSD-95α promoting and PSD-93α2 inhibiting it. The associated signaling mechanisms that control the synaptic incorporation and stabilization remain elusive. Here, we used domain swapping between the antagonizing signaling scaffolds to identify the protein motifs responsible for enhancing synaptic AMPA receptors and the associated signaling protein. We narrowed down multiple motifs in the N-terminal domain that are principally responsible for governing the enhancement by Src. Specific activation and inhibiting peptides revealed continuous activity of Src. Together, the results depict a mutual dependence of Src and PSD-95α in enhancing and maintaining synaptic AMPA receptors.

scholarly journals Synaptically Released Glutamate Does Not Overwhelm Transporters on Hippocampal Astrocytes During High-Frequency Stimulation

2000 ◽  
Vol 83 (5) ◽  
pp. 2835-2843 ◽  
Author(s):  
Jeffrey S. Diamond ◽  
Craig E. Jahr
Keyword(s):  
Synaptic Transmission ◽  
High Frequency ◽  
Hippocampal Slices ◽  
Synaptic Cleft ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Direct Role ◽  
Ca1 Region ◽  
Frequency Stimulation ◽  
Hippocampal Astrocytes

In addition to maintaining the extracellular glutamate concentration at low ambient levels, high-affinity glutamate transporters play a direct role in synaptic transmission by speeding the clearance of glutamate from the synaptic cleft and limiting the extent to which transmitter spills over between synapses. Transporters are expressed in both neurons and glia, but glial transporters are likely to play the major role in removing synaptically released glutamate from the extracellular space. The role of transporters in synaptic transmission has been studied directly by measuring synaptically activated, transporter-mediated currents (STCs) in neurons and astrocytes. Here we record from astrocytes in the CA1 region of hippocampal slices and elicit STCs with high-frequency (100 Hz) stimulus trains of varying length to determine whether transporters are overwhelmed by stimuli that induce long-term potentiation. We show that, at near-physiological temperatures (34°C), high-frequency stimulation (HFS) does not affect the rate at which transporters clear glutamate from the extrasynaptic space. Thus, although spillover between synapses during “normal” stimulation may compromise the absolute synapse specificity of fast excitatory synaptic transmission, spillover is not exacerbated during HFS. Transporter capacity is diminished somewhat at room temperature (24°C), although transmitter released during brief, “theta burst” stimulation is still cleared as quickly as following a single stimulus, even when transport capacity is partially diminished by pharmacological means.

Rapid Development of Synaptic Connections and Plasticity Between Sensory Neurons and Motor Neurons of Aplysia in Cell Culture: Implications for Learning and Regulation of Synaptic Strength

1997 ◽  
Vol 77 (5) ◽  
pp. 2316-2327 ◽  
Author(s):  
Rosalind L. Coulson ◽  
Marc Klein
Keyword(s):  
Cell Culture ◽  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Sensory Neurons ◽  
Motor Neurons ◽  
Synapse Formation ◽  
Rapid Development ◽  
Synaptic Connections ◽  
Short Term

Coulson, Rosalind L. and Marc Klein. Rapid development of synaptic connections and plasticity between sensory neurons and motor neurons of Aplysia in cell culture: implications for learning and regulation of synaptic strength. J. Neurophysiol. 77: 2316–2327, 1997. We describe here the time course of functional synapse formation and of the development of short-term synaptic plasticity at Aplysia sensorimotor synapses in cell culture, as well as the effects of blocking protein synthesis or postsynaptic receptors on the development of synaptic transmission and plasticity. We find that synaptic responses can be elicited in 50% of sensory neuron–motor neuron pairs by 1 h after cell contact and that short-term homosynaptic depression and synaptic augmentation and restoration by the endogenous facilitatory transmitter serotonin are present at the earliest stages of synapse formation. Neither block of protein synthesis with anisomycin nor block of two types of postsynaptic glutamate receptor has any effect on the development of synaptic transmission or synaptic plasticity. The rapidity of synapse formation and maturation and their independence of protein synthesis suggest that changes in the number of functional synapses could contribute to short- and intermediate-term forms of synaptic plasticity and learning.

scholarly journals A common human brain-derived neurotrophic factor polymorphism leads to sustained depression of excitatory synaptic transmission by isoflurane in hippocampus

2022 ◽  
Author(s):  
Riley A. Williams ◽  
Kenneth W. Johnson ◽  
Francis S. Lee ◽  
Hugh C. Hemmings ◽  
Jimcy Platholi
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Synaptic Vesicle ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Synaptic Function ◽  
Excitatory Synaptic Transmission ◽  
Neurological Dysfunction ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis

Multiple presynaptic and postsynaptic targets have been identified for the reversible neurophysiological effects of general anesthetics on synaptic transmission and neuronal excitability. However, the synaptic mechanisms involved in persistent depression of synaptic transmission resulting in more prolonged neurological dysfunction following anesthesia are less clear. Here, we show that brain-derived neurotrophic factor (BDNF), a growth factor implicated in synaptic plasticity and dysfunction, enhances glutamate synaptic vesicle exocytosis, and that attenuation of vesicular BDNF release by isoflurane contributes to transient depression of excitatory synaptic transmission in mice. This reduction in synaptic vesicle exocytosis was irreversible in neurons that release less endogenous BDNF due to a polymorphism (BDNF Val66Met) compared to wild-type mouse hippocampal neurons following isoflurane exposure. These effects were prevented by exogenous application of BDNF. Our findings identify a role for a common human BDNF single nucleotide polymorphism (Val66Met; rs6265) in persistent changes of synaptic function following isoflurane exposure. These persistent alterations in excitatory synaptic transmission have important implications for the role of genotype in anesthetic effects on synaptic plasticity and neurocognitive function.

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