scholarly journals Kalirin and Trio proteins serve critical roles in excitatory synaptic transmission and LTP

2016 ◽  
Vol 113 (8) ◽  
pp. 2264-2269 ◽  
Author(s):  
Bruce E. Herring ◽  
Roger A. Nicoll

The molecular mechanism underlying long-term potentiation (LTP) is critical for understanding learning and memory. CaMKII, a key kinase involved in LTP, is both necessary and sufficient for LTP induction. However, how CaMKII gives rise to LTP is currently unknown. Recent studies suggest that Rho GTPases are necessary for LTP. Rho GTPases are activated by Rho guanine exchange factors (RhoGEFs), but the RhoGEF(s) required for LTP also remain unknown. Here, using a combination of molecular, electrophysiological, and imaging techniques, we show that the RhoGEF Kalirin and its paralog Trio play critical and redundant roles in excitatory synapse structure and function. Furthermore, we show that CaMKII phosphorylation of Kalirin is sufficient to enhance synaptic AMPA receptor expression, and that preventing CaMKII signaling through Kalirin and Trio prevents LTP induction. Thus, our data identify Kalirin and Trio as the elusive targets of CaMKII phosphorylation responsible for AMPA receptor up-regulation during LTP.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pojeong Park ◽  
John Georgiou ◽  
Thomas M. Sanderson ◽  
Kwang-Hee Ko ◽  
Heather Kang ◽  
...  

AbstractLong-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or in their single channel conductance (γ). Here, we have established how these distinct synaptic processes contribute to the expression of LTP in hippocampal slices obtained from young adult rodents. LTP induced by compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involves purely an increase in N (LTPN). In contrast, either a spaced TBS, with a 10 min inter-episode interval, or a single TBS, delivered when PKA is activated, results in LTP that is associated with a transient increase in γ (LTPγ), caused by the insertion of calcium-permeable (CP)-AMPA receptors. Activation of CaMKII is necessary and sufficient for LTPN whilst PKA is additionally required for LTPγ. Thus, two mechanistically distinct forms of LTP co-exist at these synapses.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Javier Díaz-Alonso ◽  
Wade Morishita ◽  
Salvatore Incontro ◽  
Jeffrey Simms ◽  
Julia Holtzman ◽  
...  

We tested the proposal that the C-terminal domain (CTD) of the AMPAR subunit GluA1 is required for LTP. We found that a knock-in mouse lacking the CTD of GluA1 expresses normal LTP and spatial memory, assayed by the Morris water maze. Our results support a model in which LTP generates synaptic slots, which capture passively diffusing AMPARs.


Proteomes ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 40 ◽  
Author(s):  
Joongkyu Park

Synaptic plasticity has been considered a key mechanism underlying many brain functions including learning, memory, and drug addiction. An increase or decrease in synaptic activity of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) complex mediates the phenomena as shown in the cellular models of synaptic plasticity, long-term potentiation (LTP), and depression (LTD). In particular, protein phosphorylation shares the spotlight in expressing the synaptic plasticity. This review summarizes the studies on phosphorylation of the AMPAR pore-forming subunits and auxiliary proteins including transmembrane AMPA receptor regulatory proteins (TARPs) and discusses its role in synaptic plasticity.


2003 ◽  
Vol 553 (3) ◽  
pp. 843-856 ◽  
Author(s):  
Vidar Jensen ◽  
Katharina M. M. Kaiser ◽  
Thilo Borchardt ◽  
Giselind Adelmann ◽  
Andrei Rozov ◽  
...  

2003 ◽  
Vol 358 (1432) ◽  
pp. 715-720 ◽  
Author(s):  
Fabrice Duprat ◽  
Michael Daw ◽  
Wonil Lim ◽  
Graham Collingridge ◽  
John Isaac

AMPA-type glutamate receptors mediate most fast excitatory synaptic transmissions in the mammalian brain. They are critically involved in the expression of long-term potentiation and long-term depression, forms of synaptic plasticity that are thought to underlie learning and memory. A number of synaptic proteins have been identified that interact with the intracellular C-termini of AMPA receptor subunits. Here, we review recent studies and present new experimental data on the roles of these interacting proteins in regulating the AMPA receptor function during basal synaptic transmission and plasticity.


2017 ◽  
Vol 13 (7S_Part_20) ◽  
pp. P989-P989
Author(s):  
Athena Ching Jung Wang ◽  
Ron Freund ◽  
Christina M. Coughlan ◽  
Esteban M. Lucero ◽  
Mark DellAcqua ◽  
...  

2004 ◽  
Vol 91 (4) ◽  
pp. 1545-1555 ◽  
Author(s):  
Qiang Li ◽  
Shirley Guo-Ross ◽  
Darrell V. Lewis ◽  
Dennis Turner ◽  
Aaron M. White ◽  
...  

Choline, a compound present in many foods, has recently been classified as an essential nutrient for humans. Studies with animal models indicate that the availability of choline during the prenatal period influences neural and cognitive development. Specifically, prenatal choline supplementation has been shown to enhance working memory and hippocampal long-term potentiation (LTP) in adult offspring. However, the cellular mechanisms underlying these effects remain unclear. Here we report that choline supplementation, during a 6-day gestational period, results in greater excitatory responsiveness, reduced slow afterhyperpolarizations (sAHPs), enhanced afterdepolarizing potentials (ADPs), larger somata, and greater basal dendritic arborization among hippocampal CA1 pyramidal cells studied postnatally in juvenile rats (20–25 days of age). These data indicate that dietary supplementation with a single nutrient, choline, during a brief, critical period of prenatal development, alters the structure and function of hippocampal pyramidal cells.


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