cGMP Signalling in the Mammalian Brain: Role in Synaptic Plasticity and Behaviour

Author(s):  
Thomas Kleppisch ◽  
Robert Feil
2022 ◽  
Vol 23 (2) ◽  
pp. 840
Author(s):  
Li-Min Mao ◽  
Alaya Bodepudi ◽  
Xiang-Ping Chu ◽  
John Q. Wang

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.


2020 ◽  
Vol 382 (1) ◽  
pp. 161-172 ◽  
Author(s):  
Susanne Meis ◽  
Thomas Endres ◽  
Volkmar Lessmann

Abstract The amygdala is a central hub for fear learning assessed by Pavlovian fear conditioning. Indeed, the prevailing hypothesis that learning and memory are mediated by changes in synaptic strength was shown most convincingly at thalamic and cortical afferents to the lateral amygdala. The neurotrophin brain-derived neurotrophic factor (BDNF) is known to regulate synaptic plasticity and memory formation in many areas of the mammalian brain including the amygdala, where BDNF signalling via tropomyosin-related kinase B (TrkB) receptors is prominently involved in fear learning. This review updates the current understanding of BDNF/TrkB signalling in the amygdala related to fear learning and extinction. In addition, actions of proBDNF/p75NTR and NGF/TrkA as well as NT-3/TrkC signalling in the amygdala are introduced.


2014 ◽  
Vol 369 (1652) ◽  
pp. 20130515 ◽  
Author(s):  
Ayla Aksoy-Aksel ◽  
Federico Zampa ◽  
Gerhard Schratt

MicroRNAs (miRNAs) are rapidly emerging as central regulators of gene expression in the postnatal mammalian brain. Initial studies mostly focused on the function of specific miRNAs during the development of neuronal connectivity in culture, using classical gain- and loss-of-function approaches. More recently, first examples have documented important roles of miRNAs in plastic processes in intact neural circuits in the rodent brain related to higher cognitive abilities and neuropsychiatric disease. At the same time, evidence is accumulating that miRNA function itself is subjected to sophisticated control mechanisms engaged by the activity of neural circuits. In this review, we attempt to pay tribute to this mutual relationship between miRNAs and synaptic plasticity. In particular, in the first part, we summarize how neuronal activity influences each step in the lifetime of miRNAs, including the regulation of transcription, maturation, gene regulatory function and turnover in mammals. In the second part, we discuss recent examples of miRNA function in synaptic plasticity in rodent models and their implications for higher cognitive function and neurological disorders, with a special emphasis on epilepsy as a disorder of abnormal nerve cell activity.


Parasitology ◽  
2019 ◽  
Vol 146 (12) ◽  
pp. 1571-1577 ◽  
Author(s):  
Sunil Kumar Singh ◽  
Hemlata Dwivedi ◽  
Sarika Gunjan ◽  
Bhavana Singh Chauhan ◽  
Swaroop Kumar Pandey ◽  
...  

AbstractCerebral malaria (CM) is the severe neurological complication causing acute non-traumatic encephalopathy in tropical countries. The mechanisms underlying the fatal cerebral complications are still not fully understood. Glutamate, a major excitatory neurotransmitter in the central nervous system of the mammalian brain, plays a key role in the development of neuronal cells, motor function, synaptic plasticity, learning and memory processes under normal physiological conditions. The subtypes of ionotropic glutamate receptor are N-methyl-D-aspartate receptors (NMDARs) which are involved in cellular mechanisms of learning and memory, synaptic plasticity and also mediate excitotoxic neuronal injury. In the present study, we found that glutamate level in synaptosomes, as well as expression of NMDAR, was elevated during the extreme condition of CM in C57BL6 mice. Arteether at 50 mg kg−1× 1, 25 mg kg−1× 2, days decreased the NMDAR expression and increased the overall survival of the experimental CM mice.


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.


2009 ◽  
Vol 10 (9) ◽  
pp. 647-658 ◽  
Author(s):  
Anthony Holtmaat ◽  
Karel Svoboda

2008 ◽  
Vol 99 (4) ◽  
pp. 2026-2032 ◽  
Author(s):  
Long-Jun Wu ◽  
Min Zhuo

Microglia are well known for their roles in brain injuries and infections. However, there is no function attributes to resting microglia thus far. Here we performed a combination of simultaneous electrophysiology and time-lapse confocal imaging in green fluorescent protein–labeled microglia in acute hippocampal slices. In contrast to CA1 neurons, microglia showed no spontaneous or evoked synaptic currents. Neither glutamate- nor GABA-induced current/chemotaxis of microglia was detected. Strong tetanic stimulation of Schaffer-collateral pathways that induce CA1 long-term potentiation did not affect microglial motilities. Our results suggest that microglia are highly reserved for neuronal protective function but not synaptic plasticity in the brain.


1999 ◽  
Vol 77 (9) ◽  
pp. 735-737 ◽  
Author(s):  
John TR Isaac ◽  
Roger A Nicoll ◽  
Robert C Malenka

Excitatory synaptic transmission in the mammalian brain is mediated primarily by α-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors that are thought to be co-localized at individual synapses. However, recent electrophysiological and anatomical data suggest that the synaptic localization of AMPA and NMDA receptors may be independently regulated by neural activity. These data are reviewed here and the implications of these findings for the mechanisms underlying synaptic plasticity are discussed.Key words: glutamate receptor, long-term potentiation (LTP), synaptic plasticity, hippocampus, cortex.


2017 ◽  
Author(s):  
Naoki Hiratani ◽  
Tomoki Fukai

AbstractRecent experimental studies suggest that, in cortical microcircuits of the mammalian brain, the majority of neuron-to-neuron connections are realized by multiple synapses. However, it is not known whether such redundant synaptic connections provide any functional benefit. Here, we show that redundant synaptic connections enable near-optimal learning in cooperation with synaptic rewiring. By constructing a simple dendritic neuron model, we demonstrate that with multisynaptic connections, synaptic plasticity approximates a sample-based Bayesian filtering algorithm known as particle filtering, and wiring plasticity implements its resampling process. Applying the proposed framework to a detailed single neuron model, we show that the model accounts for many experimental observations, including the dendritic position dependence of spike-timing-dependent plasticity, and the functional synaptic organization on the dendritic tree based on the stimulus selectivity of presynaptic neurons. Our study provides a novel conceptual framework for synaptic plasticity and rewiring.


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