scholarly journals Differences in chloride gradients allow for three distinct types of synaptic modulation by endocannabinoids

2016 ◽  
Vol 116 (2) ◽  
pp. 619-628 ◽  
Author(s):  
Yanqing Wang ◽  
Brian D. Burrell
Keyword(s):  
Neural Circuit ◽  
Critical Role ◽  
Low Frequency ◽  
Inhibitory Synapses ◽  
Primary Role ◽  
Synaptic Modulation ◽  
Hirudo Verbana ◽  
Frequency Stimulation ◽  
Circuit Output

Endocannabinoids can elicit persistent depression of excitatory and inhibitory synapses, reducing or enhancing (disinhibiting) neural circuit output, respectively. In this study, we examined whether differences in Cl−gradients can regulate which synapses undergo endocannabinoid-mediated synaptic depression vs. disinhibition using the well-characterized central nervous system (CNS) of the medicinal leech, Hirudo verbana. Exogenous application of endocannabinoids or capsaicin elicits potentiation of pressure (P) cell synapses and depression of both polymodal (Npoly) and mechanical (Nmech) nociceptive synapses. In P synapses, blocking Cl−export prevented endocannabinoid-mediated potentiation, consistent with a disinhibition process that has been indicated by previous experiments. In Nmechneurons, which are depolarized by GABA due to an elevated Cl−equilibrium potentials (ECl), endocannabinoid-mediated depression was prevented by blocking Cl−import, indicating that this decrease in synaptic signaling was due to depression of excitatory GABAergic input (disexcitation). Npolyneurons are also depolarized by GABA, but endocannabinoids elicit depression in these synapses directly and were only weakly affected by disruption of Cl−import. Consequently, the primary role of elevated EClmay be to protect Npolysynapses from disinhibition. All forms of endocannabinoid-mediated plasticity required activation of transient potential receptor vanilloid (TRPV) channels. Endocannabinoid/TRPV-dependent synaptic plasticity could also be elicited by distinct patterns of afferent stimulation with low-frequency stimulation (LFS) eliciting endocannabinoid-mediated depression of Npolysynapses and high-frequency stimulus (HFS) eliciting endocannabinoid-mediated potentiation of P synapses and depression of Nmechsynapses. These findings demonstrate a critical role of differences in Cl−gradients between neurons in determining the sign, potentiation vs. depression, of synaptic modulation under normal physiological conditions.

scholarly journals Endocannabinoid-mediated potentiation of nonnociceptive synapses contributes to behavioral sensitization

2018 ◽  
Vol 119 (2) ◽  
pp. 641-651 ◽  
Author(s):  
Yanqing Wang ◽  
Brian D. Burrell
Keyword(s):  
Behavioral Sensitization ◽  
Neural Circuit ◽  
Critical Role ◽  
Inhibitory Synapses ◽  
Noxious Stimulation ◽  
Direct Stimulation ◽  
Bath Application ◽  
Hirudo Verbana ◽  
Nociceptive Afferents ◽  
Circuit Output

Endocannabinoids, such as 2-arachidonoyl glycerol (2-AG) and anandamide, can elicit long-term depression of both excitatory and inhibitory synapses. This latter effect will result in disinhibition and would therefore be expected to produce an increase in neural circuit output. However, there have been no examples directly linking endocannabinoid-mediated disinhibition to a change in a functional neurobehavioral circuit. The present study uses the well-characterized central nervous system of the medicinal leech, Hirudo verbana, to examine the functional/behavioral relevance of endocannabinoid modulation of an identified afferent synapse. Bath application of 2-AG potentiates synaptic transmission by pressure-sensitive sensory neurons (P cells) as well as the magnitude of the defensive shortening reflex elicited by P-cell stimulation. This potentiation requires activation of TRPV-like channels. Endocannabinoid/TRPV signaling was found to produce sensitization of the shortening reflex elicited by either direct stimulation of nearby nociceptive afferents (N cells) or noxious stimulation applied to skin several segments away. In both cases, heterosynaptic potentiation of P-cell synapses was observed in parallel with an increase in the magnitude of elicited shortening and both synaptic and behavioral effects were blocked by pharmacological inhibition of 2-AG synthesis or TRPV-like channel activation. Serotonin (5-HT) is known to play a critical role in sensitization in Hirudo and other animals, and the 5-HT2 receptor antagonist ritanserin also blocked behavioral sensitization and the accompanying synaptic potentiation. These findings suggest a novel, endocannabinoid-mediated contribution to behavioral sensitization that may interact with known 5-HT-dependent modulatory processes. NEW & NOTEWORTHY There is considerable interest in the analgesic potential of cannabinoids. However, there is evidence that the cannabinoid system can have both pro- and antinociceptive effects. This study examines how an endogenous cannabinoid transmitter can potentiate nonnociceptive synapses and enhance their capacity to elicit a nocifensive behavioral response.

Role of fascia in maintenance of muscle tension and pressure

1981 ◽  
Vol 51 (2) ◽  
pp. 317-320 ◽  
Author(s):  
S. R. Garfin ◽  
C. M. Tipton ◽  
S. J. Mubarak ◽  
S. L. Woo ◽  
A. R. Hargens ◽  
...  
Keyword(s):  
High Frequency ◽  
Muscle Tension ◽  
Fluid Pressure ◽  
Low Frequency ◽  
Testing Procedure ◽  
Force Transducer ◽  
High Frequency Stimulation ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation

The effect of fasciotomy on muscle tension (measured by a force transducer attached to the tendon) and interstitial fluid pressure (measured by Wick catheters in the muscle belly) was studied in the anterolateral compartments of 13 dog hindlimbs. Muscle tension and pressure were monitored in the tibialis cranialis muscle after low- and high-frequency stimulation of the peroneal nerve to produce twitch- and tetanic-type contractions. Fasciotomy decreased muscle force during the low-frequency stimulation by 16% (35.3 +/- 4.9 to 28.4 +/- 3.9 N) and during the high-frequency stimulation by 10% (60.8 %/- 4.9 to 54.8 +/- 3.9 N). Muscle pressure decreased 50% after fasciotomy under both conditions, 15 +/- 2 to 6 +/- 1 mmHg and 84 +/- 17 to 41 +/- 8 mmHg), respectively. Repeated functional evaluations during the testing procedure indicated that muscle fatigue was not a major factor in these results. It was concluded that fascia is important in the development of muscle tension and changes in interstitial pressure. Furthermore, the results raised questions concerning the merits of performing a fasciotomy for athletes with a compartment syndrome.

Abstract P158: MicroRNA-22 Modulates Cardiac Gene Expression and Controls Compensation to Hemodynamic Stress in Mice

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Priyatansh Gurha ◽  
Robert Kelm ◽  
Mark Entman ◽  
George Taffet ◽  
Allan Bradley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Critical Role ◽  
Cardiac Contractility ◽  
Pressure Overload ◽  
Mouse Heart ◽  
Primary Role ◽  
Translational Repressor ◽  
Muscle Gene Expression ◽  
Hemodynamic Stress

Recent evidence suggests that miRNAs play an important role in cardiac morphogenesis and pathophyiology of heart failure. To explore the role of miR-22 in the mouse heart physiology, we generated miR-22 null (KO) mice. Although, miR-22 KO mice showed normal cardiac structure and function at baseline, these mice are sensitized to maladaptive remodeling (cardiac dilation) and decompensation in response to pressure overload by transverse aortic constrictions (TAC) stimulation. Genome-wide molecular analysis of KO hearts revealed attenuated expression of numerous CarG-dependent genes encoding proteins that reside at the sarcomeric Z-disc (including Myh7, Acta1, Mlp, Melusin, MyoZ2) indicating that miR-22 is required for optimum muscle gene expression. Alterations in sarcomeric gene expression is especially interesting as this suggests a primary role of miR-22 in controlling cardiac contractility and adaptation to stress. Targetomics analysis revealed that mechanistically this effect could be modulated in part by miR-22 target PURB (Purine Rich element binding protein B), a transcriptional/translational repressor. In conclusion we define a critical role of miR-22 in cardiac adaptation to hemodynamic stress. Furthermore, these data provides a previously unseen essential molecular mechanism that underlies homeostatic control of sarcomeric protein expression in the heart.

The role of galanin receptors in anticonvulsant effects of low-frequency stimulation in perforant path–kindled rats

Neuroscience ◽  
2007 ◽  
Vol 150 (2) ◽  
pp. 396-403 ◽  
Author(s):  
M. Sadegh ◽  
J. Mirnajafi-Zadeh ◽  
M. Javan ◽  
Y. Fathollahi ◽  
M. Mohammad-Zadeh ◽  
...  
Keyword(s):  
Low Frequency ◽  
Perforant Path ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation ◽  
Galanin Receptors ◽  
Anticonvulsant Effects

scholarly journals The critical role of ASD-related gene CNTNAP3 in regulating synaptic development and social behavior in mice

2018 ◽  
Author(s):  
Da-li Tong ◽  
Rui-guo Chen ◽  
Yu-lan Lu ◽  
Wei-ke Li ◽  
Yue-fang Zhang ◽  
...  
Keyword(s):  
Critical Role ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Inhibitory Synapses ◽  
Scaffolding Proteins ◽  
Loss Of Function ◽  
Chinese Han

AbstractAccumulated genetic evidences indicate that the contactin associated protein-like (CNTNAP) family is implicated in autism spectrum disorders (ASD). In this study, we identified genetic mutations in the CNTNAP3 gene from Chinese Han ASD cohorts and Simons Simplex Collections. We found that CNTNAP3 interacted with synaptic adhesion proteins Neuroligin1 and Neuroligin2, as well as scaffolding proteins PSD95 and Gephyrin. Significantly, we found that CNTNAP3 played an opposite role in controlling the development of excitatory and inhibitory synapses in vitro and in vivo, in which ASD mutants exhibited loss-of-function effects. In this study, we showed that Cntnap3-null mice exhibited deficits in social interaction, spatial learning and prominent repetitive behaviors. These evidences elucidate the pivotal role of CNTNAP3 in synapse development and social behaviors, providing the mechanistic insights for ASD.

scholarly journals Does Parental Co-creation Impacts Perceived Value? A Mixed-method Study in Indian Elementary Educational Innovations

2019 ◽  
Vol 24 (1) ◽  
pp. 90-100
Author(s):  
Meeta Dasgupta ◽  
Anupama Prashar
Keyword(s):  
Critical Role ◽  
Perceived Value ◽  
Primary Role ◽  
Educational Effectiveness ◽  
Educational Innovations ◽  
School Services ◽  
Business Units ◽  
Role Of Parents ◽  
The Impact

Research on building innovative practices for enhancing the educational effectiveness has gained momentum. Schools as business units play a critical role in building effectiveness. Empirical investigation on the role of parents, the primary customers taking decisions with respect to availing school services for their children, as co-creators in conceptualizing and executing educational innovations is thin. To bridge this research gap, a mixed methods study was conducted on a sample of elementary schools in India. The study also investigated the impact of parents’ involvement on their perceived value and satisfaction. The results suggested that schools are undertaking various innovative initiatives in which parents play a primary role in execution both at home and in the school. It was found that parents’ perception of value for innovative practices introduced by the schools is high, irrespective of their low involvement in the conceptualization stage. The findings also indicated that parental involvement in the execution stage of the initiatives impacts their perceived value more than at the conceptualization stage.

scholarly journals Contribution of the Periplasmic Chaperone Skp to Efficient Presentation of the Autotransporter IcsA on the Surface of Shigella flexneri

2008 ◽  
Vol 191 (3) ◽  
pp. 815-821 ◽  
Author(s):  
Jennifer K. Wagner ◽  
Jason E. Heindl ◽  
Andrew N. Gray ◽  
Sumita Jain ◽  
Marcia B. Goldberg
Keyword(s):  
Outer Membrane ◽  
Shigella Flexneri ◽  
Critical Role ◽  
Amino Terminus ◽  
Primary Role ◽  
Membrane Anchor ◽  
Bacterial Surface ◽  
Periplasmic Chaperone ◽  
Cell Spread

ABSTRACT IcsA is an outer membrane protein in the autotransporter family that is required for Shigella flexneri pathogenesis. Following its secretion through the Sec translocon, IcsA is incorporated into the outer membrane in a process that depends on YaeT, a component of an outer membrane β-barrel insertion machinery. We investigated the role of the periplasmic chaperone Skp in IcsA maturation. Skp is required for the presentation of the mature amino terminus (alpha-domain) of IcsA on the bacterial surface and contributes to cell-to-cell spread of S. flexneri in cell culture. A mutation in skp does not prevent the insertion of the β-barrel into the outer membrane, suggesting that the primary role of Skp is the folding of the IcsA alpha-domain. In addition, the requirement for skp can be partially bypassed by disrupting icsP, an ortholog of Escherichia coli ompT, which encodes the protease that processes IcsA between the mature amino terminus and the β-barrel outer membrane anchor. These findings are consistent with a model in which Skp plays a critical role in the chaperoning of the alpha-domain of IcsA during transit through the periplasm.

scholarly journals BDNF controls bidirectional endocannabinoid-plasticity at corticostriatal synapses

2019 ◽  
Author(s):  
Giuseppe Gangarossa ◽  
Sylvie Perez ◽  
Yulia Dembitskaya ◽  
Ilya Prokin ◽  
Hugues Berry ◽  
...  
Keyword(s):  
Low Frequency ◽  
Dorsal Striatum ◽  
Brain Structures ◽  
Spike Timing ◽  
Procedural Learning ◽  
Two Photon ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation ◽  
Corticostriatal Plasticity

ABSTRACTThe dorsal striatum exhibits bidirectional corticostriatal synaptic plasticity, NMDAR- and endocannabinoids-(eCB)-mediated, necessary for the encoding of procedural learning. Therefore, characterizing factors controlling corticostriatal plasticity is of crucial importance. Brain-derived neurotrophic factor (BDNF) and its receptor, the tropomyosine receptor kinase-B (TrkB), shape striatal functions and their dysfunction deeply affect basal ganglia. BDNF/TrkB signaling controls NMDAR-plasticity in various brain structures including striatum. However, despite cross-talks between BDNF and eCBs, the role of BDNF in eCB-plasticity remains unknown. Here, we show that BDNF/TrkB signaling promotes eCB-plasticity (LTD and LTP) induced by rate-based (low-frequency stimulation) or spike-timing-based (spike-timing-dependent plasticity, STDP) paradigm in striatum. We show that TrkB activation is required for the expression and the scaling of both eCB-LTD and eCB-LTP. Using two-photon imaging of the dendritic spines combined with patch-clamp recordings, we show that TrkB activation induces an intracellular calcium boost, thus increasing eCB synthesis and release. We provide a mathematical model for the dynamics of the signaling pathways involved in corticostriatal plasticity. Finally, we show that TrkB activation allows an enlargement of the domain of expression of eCB-STDP. Our results reveal a novel role for BDNF/TrkB signaling in governing eCB-plasticity expression in striatum, and thus the engram of procedural learning.

Sign in / Sign up

Export Citation Format

Share Document