scholarly journals Joint CP-AMPA and group I mGlu receptor activation is required for synaptic plasticity in dentate gyrus fast-spiking interneurons

2014 ◽  
Vol 111 (36) ◽  
pp. 13211-13216 ◽  
Author(s):  
T. Hainmuller ◽  
K. Krieglstein ◽  
A. Kulik ◽  
M. Bartos
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Receptor Activation ◽  
Mglu Receptor ◽  
Group I ◽  
Fast Spiking

Epileptogenesis Up-Regulates Metabotropic Glutamate Receptor Activation of Sodium-Calcium Exchange Current in the Amygdala

2000 ◽  
Vol 83 (4) ◽  
pp. 2458-2462 ◽  
Author(s):  
N. Bradley Keele ◽  
Fatiha Zinebi ◽  
Volker Neugebauer ◽  
P. Shinnick-Gallagher
Keyword(s):  
Basolateral Amygdala ◽  
Metabotropic Glutamate Receptor ◽  
Partial Agonist ◽  
Brain Slices ◽  
Receptor Activation ◽  
Exchange Current ◽  
Inward Current ◽  
Mglu Receptor ◽  
Metabotropic Glutamate ◽  
Group I

Postsynaptic metabotropic glutamate (mGlu) receptor-activated inward current mediated by Na+-Ca2+ exchange was compared in basolateral amygdala (BLA) neurons from brain slices of control (naı̈ve and sham-operated) and amygdala-kindled rats. In control neurons, the mGlu agonist, quisqualate (QUIS; 1–100 μM), evoked an inward current not associated with a significant change in membrane slope conductance, measured from current-voltage relationships between −110 and −60 mV, consistent with activation of the Na+-Ca2+ exchanger. Application of the group I selective mGlu receptor agonist ( S)-3,5-dihydroxyphenylglycine [( S)-DHPG; 10–1000 μM] or the endogenous agonist, glutamate (10–1000 μM), elicited the exchange current. QUIS was more potent than either ( S)-DHPG or glutamate (apparent EC50 = 19 μM, 57 μM, and 0.6 mM, respectively) in activating the Na+-Ca2+ exchange current. The selective mGlu5 agonist, ( R,S)-2-chloro-5-hydroxyphenylglycine [( R,S)-CHPG; apparent EC50 = 2.6 mM] also induced the exchange current. The maximum response to ( R,S) -DHPG was about half of that of the other agonists suggesting partial agonist action. Concentration-response relationships of agonist-evoked inward currents were compared in control neurons and in neurons from kindled animals. The maximum value for the concentration-response relationship of the partial agonist ( S)-DHPG- (but not the full agonist- [QUIS or ( R, S)-CHPG]) induced inward current was shifted upward suggesting enhanced efficacy of this agonist in kindled neurons. Altogether, these data are consistent with a kindling-induced up-regulation of a group I mGlu-, possibly mGlu5-, mediated responses coupled to Na+-Ca2+ exchange in BLA neurons.

scholarly journals Activation of group II mGlu receptors inhibits voltage-gated Ca2+ currents in myenteric neurons

2002 ◽  
Vol 283 (6) ◽  
pp. G1282-G1289 ◽  
Author(s):  
Wei-Ping Chen ◽  
Annette L. Kirchgessner
Keyword(s):  
Calcium Channels ◽  
Rank Order ◽  
Receptor Activation ◽  
Enteric Neurons ◽  
Myenteric Neurons ◽  
Voltage Gated ◽  
Mglu Receptor ◽  
Receptor Agonists ◽  
Group I ◽  
Group Ii

The enteric nervous system (ENS) contains functional ionotropic and group I metabotropic glutamate (mGlu) receptors. In this study, we determined whether enteric neurons express group II mGlu receptors and the effects of mGlu receptor activation on voltage-gated Ca2+ currents in these cells. (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), a group II mGlu receptor agonist, reversibly suppressed the Ba2+current in myenteric neurons isolated from the guinea pig ileum. Significant inhibition was also produced by l-glutamate and the group II mGlu receptor agonists, (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG-IV) and (2S,1′S,2′S)-2-(2-carboxycyclopropyl)glycine (l-CCG-I), with a rank order potency of 2R,4R-APDC > DCG-IV >l-glutamate > l-CCG-I, and was reduced by the group II mGlu receptor antagonist LY-341495. Pretreatment of neurons with pertussis toxin (PTX) reduced the action of mGlu receptor agonists, suggesting participation of Gi/Goproteins. Finally, ω-conotoxin GVIA blocked current suppression by DCG-IV, suggesting modulation of N-type calcium channels. mGlu2/3 receptor immunoreactivity was displayed by neurons in culture and in the submucosal and myenteric plexus of the ileum. A subset of these cells displayed a glutamatergic phenotype as shown by the expression of vesicular glutamate transporter 2. These results provide the first evidence for functional group II mGlu receptors in the ENS and show that these receptors are PTX sensitive and negatively coupled to N-type calcium channels. Inhibition of N-type calcium channels produced by activation of group II mGlu receptors may modulate enteric neurotransmission.

Effects of Adult Neurogenesis on Synaptic Plasticity in the Rat Dentate Gyrus

2001 ◽  
Vol 85 (6) ◽  
pp. 2423-2431 ◽  
Author(s):  
J. S. Snyder ◽  
N. Kee ◽  
J. M. Wojtowicz
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Adult Neurogenesis ◽  
Long Term Potentiation ◽  
Receptor Blocker ◽  
Granule Neurons ◽  
Term Potentiation ◽  
Cell Recording ◽  
Similar Preparation ◽  
Nmda Receptor Blocker

Ongoing neurogenesis in the adult hippocampal dentate gyrus (DG) generates a substantial population of young neurons. This phenomenon is present in all species examined thus far, including humans. Although the regulation of adult neurogenesis by various physiologically relevant factors such as learning and stress has been documented, the functional contributions of the newly born neurons to hippocampal functions are not known. We investigated possible contributions of the newly born granule neurons to synaptic plasticity in the hippocampal DG. In the standard hippocampal slice preparation perfused with artificial cerebrospinal fluid (ACSF), a small (10%) long-term potentiation (LTP) of the evoked field potentials is seen after tetanic stimulation of the afferent medial perforant pathway (MPP). The induction of this ACSF-LTP is resistant to a N-methyl-d-aspartate (NMDA) receptor blocker,d,l-2-amino-5-phosphonovaleric acid (APV), but is completely prevented by ifenprodil, a blocker of NR2B subtype of NMDA receptors. In contrast, slices perfused with picrotoxin (PICRO), a GABA-receptor blocker, revealed a larger (40–50%), APV-sensitive but ifenprodil-insensitive LTP. The ACSF-LTP required lower frequency of stimulation and fewer stimuli for its induction than the PICRO-LTP. All these characteristics of ACSF-LTP are in agreement with the properties of the putative individual new granule neurons examined previously with the use of the whole cell recording technique in a similar preparation. A causal relationship between neurogenesis and ACSF-LTP was confirmed in experiments using low dose of gamma radiation applied to the brain 3 wk prior to the electrophysiological experiments. In these experiments, the new cell proliferation was drastically reduced and ACSF-LTP was selectively blocked. We conclude that the young, adult-generated granule neurons play a significant role in synaptic plasticity in the DG. Since DG is the major source of the afferent inputs into the hippocampus, the production and the plasticity of new neurons may have an important role in the hippocampal functions such as learning and memory.

Noradrenergic Regulation of Synaptic Plasticity in the Hippocampal CA1 Region

1997 ◽  
Vol 77 (6) ◽  
pp. 3013-3020 ◽  
Author(s):  
Hiroshi Katsuki ◽  
Yukitoshi Izumi ◽  
Charles F. Zorumski
Keyword(s):  
Synaptic Plasticity ◽  
Receptor Antagonist ◽  
Hippocampal Slices ◽  
Stimulus Frequency ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

Katsuki, Hiroshi, Yukitoshi Izumi, and Charles F. Zorumski. Noradrenergic regulation of synaptic plasticity in the hippocampal CA1 region. J. Neurophysiol. 77: 3013–3020, 1997. The effects of norepinephrine (NE) and related agents on long-lasting changes in synaptic efficacy induced by several patterns of afferent stimuli were investigated in the CA1 region of rat hippocampal slices. NE (10 μM) showed little effect on the induction of long-term potentiation (LTP) triggered by theta-burst-patterned stimulation, whereas it inhibited the induction of long-term depression (LTD) triggered by 900 pulses of 1-Hz stimulation. In nontreated slices, 900 pulses of stimuli induced LTD when applied at lower frequencies (1–3 Hz), and induced LTP when applied at a higher frequency (30 Hz). NE (10 μM) caused a shift of the frequency-response relationship in the direction preferring potentiation. The effect of NE was most prominent at a stimulus frequency of 10 Hz, which induced no changes in control slices but clearly induced LTP in the presence of NE. The facilitating effect of NE on the induction of LTP by 10-Hz stimulation was blocked by theβ-adrenergic receptor antagonist timolol (50 μM), but not by the α receptor antagonist phentolamine (50 μM), and was mimicked by the β-agonist isoproterenol (0.3 μM), but not by the α1 agonist phenylephrine (10 μM). The induction of LTD by 1-Hz stimulation was prevented by isoproterenol but not by phenylephrine, indicating that the activation of β-receptors is responsible for these effects of NE. NE (10 μM) also prevented the reversal of LTP (depotentiation) by 900 pulses of 1-Hz stimulation delivered 30 min after LTP induction. In contrast to effects on naive (nonpotentiated) synapses, the effect of NE on previously potentiated synapses was only partially mimicked by isoproterenol, but fully mimicked by coapplication of phenylephrine and isoproterenol. In addition, the effect of NE was attenuated either by phentolamine or by timolol, indicating that activation of both α1 and β-receptors is required. These results show that NE plays a modulatory role in the induction of hippocampal synaptic plasticity. Althoughβ-receptor activation is essential, α1 receptor activation is also necessary in determining effects on previously potentiated synapses.

scholarly journals Reversal of age-related oxidative stress prevents hippocampal synaptic plasticity deficits by protecting d-serine-dependent NMDA receptor activation

Aging Cell ◽  
2012 ◽  
Vol 11 (2) ◽  
pp. 336-344 ◽  
Author(s):  
Coline Haxaire ◽  
Fabrice R Turpin ◽  
Brigitte Potier ◽  
Myriam Kervern ◽  
Pierre-Marie Sinet ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Receptor Activation ◽  
Hippocampal Synaptic Plasticity ◽  
Age Related ◽  
Nmda Receptor Activation

scholarly journals Group I Metabotropic Glutamate Receptors and Interacting Partners: An Update

2022 ◽  
Vol 23 (2) ◽  
pp. 840
Author(s):  
Li-Min Mao ◽  
Alaya Bodepudi ◽  
Xiang-Ping Chu ◽  
John Q. Wang
Keyword(s):  
Synaptic Plasticity ◽  
Protein Interactions ◽  
Metabotropic Glutamate Receptors ◽  
Adaptor Proteins ◽  
Mammalian Brain ◽  
Amino Acid Residues ◽  
Protein Protein Interactions ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Associated Proteins

Group I metabotropic glutamate (mGlu) receptors (mGlu1/5 subtypes) are G protein-coupled receptors and are broadly expressed in the mammalian brain. These receptors play key roles in the modulation of normal glutamatergic transmission and synaptic plasticity, and abnormal mGlu1/5 signaling is linked to the pathogenesis and symptomatology of various mental and neurological disorders. Group I mGlu receptors are noticeably regulated via a mechanism involving dynamic protein–protein interactions. Several synaptic protein kinases were recently found to directly bind to the intracellular domains of mGlu1/5 receptors and phosphorylate the receptors at distinct amino acid residues. A variety of scaffolding and adaptor proteins also interact with mGlu1/5. Constitutive or activity-dependent interactions between mGlu1/5 and their interacting partners modulate trafficking, anchoring, and expression of the receptors. The mGlu1/5-associated proteins also finetune the efficacy of mGlu1/5 postreceptor signaling and mGlu1/5-mediated synaptic plasticity. This review analyzes the data from recent studies and provides an update on the biochemical and physiological properties of a set of proteins or molecules that interact with and thus regulate mGlu1/5 receptors.

scholarly journals Levetiracetam Reduced the Basal Excitability of the Dentate Gyrus without Restoring Impaired Synaptic Plasticity in Rats with Temporal Lobe Epilepsy

2020 ◽  
Vol 10 (9) ◽  
pp. 634
Author(s):  
Guillermo González-H ◽  
Itzel Jatziri Contreras-García ◽  
Karla Sánchez-Huerta ◽  
Claudio M. T. Queiroz ◽  
Luis Ricardo Gallardo Gudiño ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Temporal Lobe ◽  
Focal Epilepsy ◽  
Chronic Phase ◽  
Long Term Potentiation ◽  
Excitatory Postsynaptic Potential ◽  
Output Curve

Temporal lobe epilepsy (TLE), the most common type of focal epilepsy, affects learning and memory; these effects are thought to emerge from changes in synaptic plasticity. Levetiracetam (LEV) is a widely used antiepileptic drug that is also associated with the reversal of cognitive dysfunction. The long-lasting effect of LEV treatment and its participation in synaptic plasticity have not been explored in early chronic epilepsy. Therefore, through the measurement of evoked field potentials, this study aimed to comprehensively identify the alterations in the excitability and the short-term (depression/facilitation) and long-term synaptic plasticity (long-term potentiation, LTP) of the dentate gyrus of the hippocampus in a lithium–pilocarpine rat model of TLE, as well as their possible restoration by LEV (1 week; 300 mg/kg/day). TLE increased the population spike (PS) amplitude (input/output curve); interestingly, LEV treatment partially reduced this hyperexcitability. Furthermore, TLE augmented synaptic depression, suppressed paired-pulse facilitation, and reduced PS-LTP; however, LEV did not alleviate such alterations. Conversely, the excitatory postsynaptic potential (EPSP)-LTP of TLE rats was comparable to that of control rats and was decreased by LEV. LEV caused a long-lasting attenuation of basal hyperexcitability but did not restore impaired synaptic plasticity in the early chronic phase of TLE.

Sign in / Sign up

Export Citation Format

Share Document