Faculty Opinions recommendation of STIM1 controls neuronal Ca²⁺ signaling, mGluR1-dependent synaptic transmission, and cerebellar motor behavior.

Author(s):  
Masanobu Kano
2015 ◽  
Vol 112 (4) ◽  
pp. E371-E379 ◽  
Author(s):  
Maya Yamazaki ◽  
Claire E. Le Pichon ◽  
Alexander C. Jackson ◽  
Manuel Cerpas ◽  
Kenji Sakimura ◽  
...  

Transmembrane AMPA receptor regulatory proteins (TARPs) play an essential role in excitatory synaptic transmission throughout the central nervous system (CNS) and exhibit subtype-specific effects on AMPA receptor (AMPAR) trafficking, gating, and pharmacology. The function of TARPs has largely been determined through work on canonical type I TARPs such as stargazin (TARP γ-2), absent in the ataxic stargazer mouse. Little is known about the function of atypical type II TARPs, such as TARP γ-7, which exhibits variable effects on AMPAR function. Because γ-2 and γ-7 are both strongly expressed in multiple cell types in the cerebellum, we examined the relative contribution of γ-2 and γ-7 to both synaptic transmission in the cerebellum and motor behavior by using both the stargazer mouse and a γ-7 knockout (KO) mouse. We found that the loss of γ-7 alone had little effect on climbing fiber (cf) responses in Purkinje neurons (PCs), yet the additional loss of γ-2 all but abolished cf responses. In contrast, γ-7 failed to make a significant contribution to excitatory transmission in stellate cells and granule cells. In addition, we generated a PC-specific deletion of γ-2, with and without γ-7 KO background, to examine the relative contribution of γ-2 and γ-7 to PC-dependent motor behavior. Selective deletion of γ-2 in PCs had little effect on motor behavior, yet the additional loss of γ-7 resulted in a severe disruption in motor behavior. Thus, γ-7 is capable of supporting a component of excitatory transmission in PCs, sufficient to maintain essentially normal motor behavior, in the absence of γ-2.


2021 ◽  
Author(s):  
Pravat Dhakal ◽  
Sana Chaudhry ◽  
Kevin M. Collins

Activated Gαq signals through Phospholipase-Cβ (PLCβ) and Trio, a Rho GTPase exchange factor (RhoGEF), but how these two effector pathways promote synaptic transmission remains poorly understood. We used the egg-laying behavior circuit of C. elegans to determine whether PLCβ and Trio mediate serotonin and Gαq signaling through independent or related biochemical pathways. Using genetic rescue experiments, we find that PLCβ functions in neurons while Trio functions in both neurons and the postsynaptic vulval muscles. While Gαq, PLCβ, and Trio RhoGEF mutants all fail to lay eggs in response to serotonin, optogenetic stimulation of the serotonin releasing HSN command neurons restores egg laying only in PLCβ mutants. Vulval muscle Ca2+ activity remained in PLCβ mutants but was eliminated in strong Gαq and Trio RhoGEF mutants. Exogenous treatment with Phorbol esters that mimic Diacylglycerol (DAG), a product of PIP2 hydrolysis, rescued egg-laying circuit activity and behavior defects of Gαq signaling mutants, suggesting both Phospholipase C and Rho signaling promote synaptic transmission and egg-laying via DAG production. DAG has been proposed to activate effectors including UNC-13, however, we find that phorbol esters, but not serotonin, stimulate egg laying in unc-13 mutants. Together, these results show that serotonin signaling through Gαq and PLCβ modulates UNC-13 activity to promote neurotransmitter release. Serotonin also signals through Gαq, Trio RhoGEF, and an unidentified PMA-responsive effector to promote postsynaptic muscle excitability. Thus, the same neuromodulator serotonin can signal in distinct cells and effector pathways to activate a motor behavior circuit.


Neuron ◽  
2014 ◽  
Vol 82 (3) ◽  
pp. 635-644 ◽  
Author(s):  
Jana Hartmann ◽  
Rosa M. Karl ◽  
Ryan P.D. Alexander ◽  
Helmuth Adelsberger ◽  
Monika S. Brill ◽  
...  

2010 ◽  
Vol 24 (2) ◽  
pp. 76-82 ◽  
Author(s):  
Martin M. Monti ◽  
Adrian M. Owen

Recent evidence has suggested that functional neuroimaging may play a crucial role in assessing residual cognition and awareness in brain injury survivors. In particular, brain insults that compromise the patient’s ability to produce motor output may render standard clinical testing ineffective. Indeed, if patients were aware but unable to signal so via motor behavior, they would be impossible to distinguish, at the bedside, from vegetative patients. Considering the alarming rate with which minimally conscious patients are misdiagnosed as vegetative, and the severe medical, legal, and ethical implications of such decisions, novel tools are urgently required to complement current clinical-assessment protocols. Functional neuroimaging may be particularly suited to this aim by providing a window on brain function without requiring patients to produce any motor output. Specifically, the possibility of detecting signs of willful behavior by directly observing brain activity (i.e., “brain behavior”), rather than motoric output, allows this approach to reach beyond what is observable at the bedside with standard clinical assessments. In addition, several neuroimaging studies have already highlighted neuroimaging protocols that can distinguish automatic brain responses from willful brain activity, making it possible to employ willful brain activations as an index of awareness. Certainly, neuroimaging in patient populations faces some theoretical and experimental difficulties, but willful, task-dependent, brain activation may be the only way to discriminate the conscious, but immobile, patient from the unconscious one.


1970 ◽  
Vol 15 (6) ◽  
pp. 431-431
Author(s):  
GARTH J. THOMAS

1981 ◽  
Vol 26 (4) ◽  
pp. 258-259
Author(s):  
Jack A. Adams
Keyword(s):  

1981 ◽  
Vol 26 (11) ◽  
pp. 884-884
Author(s):  
Waneen Wyrick Spirduso
Keyword(s):  

1983 ◽  
Vol 28 (10) ◽  
pp. 785-786
Author(s):  
Beth Kerr
Keyword(s):  

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