Short- and long-term depression at glutamatergic synapses on hippocampal interneurons by group I mGluR activation

2011 ◽  
Vol 60 (5) ◽  
pp. 748-756 ◽  
Author(s):  
Caroline Le Duigou ◽  
Thomas Holden ◽  
Dimitri M. Kullmann
2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Mario Gruppo ◽  
Francesca Tolin ◽  
Boris Franzato ◽  
Pierluigi Pilati ◽  
Ylenia Camilla Spolverato ◽  
...  

Background. Although mortality and morbidity of pancreatoduodenectomy (PD) have improved significantly over the past years, the impact of age for patients undergoing PD is still debated. This study is aimed at analyzing short- and long-term outcomes of PD in elderly patients. Methods. 124 consecutive patients who have undergone PD for pancreas neoplasms in our center between 2012 and 2017 were analyzed. Patients were divided into two groups: group I (<75 years) and group II (≥75 years). Demographic features and intraoperative and clinical-pathological data were collected. Primary endpoints were perioperative morbidity and mortality; complications were classified according to the Clavien-Dindo Score. Secondary endpoints included feasibility of adjuvant treatment and overall survival rates. Results. A total of 106 patients were included in this study. There were 73 (68.9%) patients in group I and 33 (31.1%) in group II. Perioperative deceases were 4 (3.6%), and postoperative pancreatic fistulas were 34 (32.1%). Significant difference between two groups was demonstrated for the ASA Score (p=0.004), Karnofsky Score (p=0.025), preoperative jaundice (p=0.004), and pulmonary complications (p=0.034). No significance was shown for diabetes, radicality of resection, stage of disease, operative time, length of stay, postoperative complications according to the Clavien-Dindo Score, postoperative mortality, pancreatic fistula, and reoperation rates. 69.9% of the patients in group I underwent adjuvant treatment vs. 39.4% of the older ones (p=0.012). Mean overall survival was 28.5 months in group I vs. 22 months in group II (p=0.909). Conclusion. PD can be performed safely in elderly patients. Advanced age should not be an absolute contraindication for PD, even if greater frailty should be considered. The outcome of elderly patients who have undergone PD is similar to that of younger patients, even though adjuvant treatment administration is significantly lower, demonstrating that surgery remains the main therapeutic option.


2001 ◽  
Vol 86 (5) ◽  
pp. 2405-2412 ◽  
Author(s):  
Ki-Wug Sung ◽  
Sukwoo Choi ◽  
David M. Lovinger

Activation of metabotropic glutamate receptors (mGluRs), which are coupled to G proteins, has important roles in certain forms of synaptic plasticity including corticostriatal long-term depression (LTD). In the present study, extracellular field potential and whole cell voltage-clamp recording techniques were used to investigate the effect of mGluR antagonists with different subtype specificity on high-frequency stimulation (HFS)-induced LTD of synaptic transmission in the striatum of brain slices obtained from 15-to 25-day-old rats. Induction of LTD was prevented during exposure to the nonselective mGluR antagonist (RS)-α-methyl-4-carboxyphenylglycine (500 μM). The group I mGluR-selective antagonists ( S)-4-carboxy-phenylglycine (50 μM) and (RS)-1-aminoindan-1,5-dicarboxylic acid (100 μM) prevented induction of LTD when applied before and during HFS. The mGluR1-selective antagonist 7-(Hydroxyimino) cyclopropa[b]chromen-1a-carboxylate ethyl ester (80 μM) also blocked LTD induction. Unexpectedly, the mGluR5-selective antagonist 2-methyl-6-(phenylethyl)-pyridine (10 μM) also prevented LTD induction. The group II mGluR antagonist LY307452 (10 μM) did not block LTD induction at corticostriatal synapses, but LY307452 was able to block transient synaptic depression induced by the group II agonist LY314593. None of the antagonists had any effect on basal synaptic transmission at the concentrations used, and mGluR antagonists did not reverse LTD when applied beginning 20 min after HFS. These results suggest that both group I mGluR subtypes contribute to the induction of LTD at corticostriatal synapses.


2015 ◽  
Vol 22 (2) ◽  
pp. 275-290 ◽  
Author(s):  
Tiffany A. Wills ◽  
Anthony J. Baucum ◽  
Katherine M. Holleran ◽  
Yaoyi Chen ◽  
Johanna G. Pasek ◽  
...  

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Yihui Cui ◽  
Ilya Prokin ◽  
Hao Xu ◽  
Bruno Delord ◽  
Stephane Genet ◽  
...  

Synaptic plasticity is a cardinal cellular mechanism for learning and memory. The endocannabinoid (eCB) system has emerged as a pivotal pathway for synaptic plasticity because of its widely characterized ability to depress synaptic transmission on short- and long-term scales. Recent reports indicate that eCBs also mediate potentiation of the synapse. However, it is not known how eCB signaling may support bidirectionality. Here, we combined electrophysiology experiments with mathematical modeling to question the mechanisms of eCB bidirectionality in spike-timing dependent plasticity (STDP) at corticostriatal synapses. We demonstrate that STDP outcome is controlled by eCB levels and dynamics: prolonged and moderate levels of eCB lead to eCB-mediated long-term depression (eCB-tLTD) while short and large eCB transients produce eCB-mediated long-term potentiation (eCB-tLTP). Moreover, we show that eCB-tLTD requires active calcineurin whereas eCB-tLTP necessitates the activity of presynaptic PKA. Therefore, just like glutamate or GABA, eCB form a bidirectional system to encode learning and memory.


1999 ◽  
Vol 82 (6) ◽  
pp. 3594-3597 ◽  
Author(s):  
Nathaniel B. Sawtell ◽  
Kimberly M. Huber ◽  
John C. Roder ◽  
Mark F. Bear

We tested the role of group I mGluRs in the induction of long-term depression (LTD) in the visual cortex, using the novel mGluR antagonist LY341495 and mice lacking mGluR5, the predominant phosphoinositide (PI)-linked mGluR in the visual cortex. We find that LY341495 is a potent blocker of glutamate-stimulated PI hydrolysis in visual cortical synaptoneurosomes, and that it effectively antagonizes the actions of the mGluR agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (ACPD) on synaptic transmission in visual cortical slices. However, LY341495 has no effect on the induction of LTD by low-frequency stimulation. Furthermore, mice lacking mGluR5 show normal NMDA receptor-dependent LTD. These results indicate that group I mGluR activation is not required for the induction of NMDA receptor-dependent LTD in the visual cortex.


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