Hippocampal Wdr1 Deficit Impairs Learning and Memory by Perturbing F-actin Depolymerization in Mice

2018 ◽  
Vol 29 (10) ◽  
pp. 4194-4207
Author(s):  
Jie Wang ◽  
Xiao-Lin Kou ◽  
Cheng Chen ◽  
Mei Wang ◽  
Cui Qi ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Conditional Knockout ◽  
Actin Dynamics ◽  
Term Potentiation ◽  
The Central Nervous System ◽  
Ca1 Area

Abstract WD repeat protein 1 (Wdr1), known as a cofactor of actin-depolymerizing factor (ADF)/cofilin, is conserved among eukaryotes, and it plays a critical role in the dynamic reorganization of the actin cytoskeleton. However, the function of Wdr1 in the central nervous system remains elusive. Using Wdr1 conditional knockout mice, we demonstrated that Wdr1 plays a significant role in regulating synaptic plasticity and memory. The knockout mice exhibited altered reversal spatial learning and fear responses. Moreover, the Wdr1 CKO mice showed significant abnormalities in spine morphology and synaptic function, including enhanced hippocampal long-term potentiation and impaired long-term depression. Furthermore, we observed that Wdr1 deficiency perturbed actin rearrangement through regulation of the ADF/cofilin activity. Taken together, these results indicate that Wdr1 in the hippocampal CA1 area plays a critical role in actin dynamics in associative learning and postsynaptic receptor availability.

Immunology relevant to neuropsychiatry

2020 ◽  
pp. 151-160
Author(s):  
Rachel Patel ◽  
Neil A. Harrison
Keyword(s):  
New Technologies ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Psychiatric Disease ◽  
Cns Development ◽  
Term Potentiation ◽  
The Central Nervous System ◽  
Neurological Processes ◽  
Privileged Site

Neuroimmunology is a rapidly developing field, challenging the age-old notion of the central nervous system (CNS) as an immune-privileged site with limited immune function. In the last two decades, new technologies have demonstrated that immune processes play a critical role in normal CNS development, are integral to fundamental neurological processes, such as long-term potentiation and synaptic plasticity, and are implicated in pathologies ranging from narcolepsy to depression, schizophrenia, and Alzheimer’s disease. They indicate that immunology and mental illness are fundamentally intertwined, opening exciting new avenues for future immunotherapies tackling psychiatric disease. Here the chapter reviews basic immune mechanisms, specifically highlighting processes that are of particular relevance to neuropsychiatry. It is hoped that this chapter will serve as an accessible primer to the related fields of psychoneuroimmunology and immunopsychiatry and stimulate readers’ interest in this increasingly important and fast-evolving field.

scholarly journals AMPA receptor trafficking and long-term potentiation

2003 ◽  
Vol 358 (1432) ◽  
pp. 707-714 ◽  
Author(s):  
Roberto Malinow
Keyword(s):  
Ampa Receptor ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Receptor Trafficking ◽  
Synaptic Function ◽  
Term Potentiation ◽  
The Subject ◽  
Activity Dependent ◽  
Ampa Receptor Trafficking

Activity-dependent changes in synaptic function are believed to underlie the formation of memories. A prominent example is long-term potentiation (LTP), whose mechanisms have been the subject of considerable scrutiny over the past few decades. I review studies from our laboratory that support a critical role for AMPA receptor trafficking in LTP and experience-dependent plasticity.

scholarly journals Defective place cell activity in nociceptin receptor knockout mice with elevated NMDA receptor-dependent long-term potentiation

2005 ◽  
Vol 565 (2) ◽  
pp. 579-591 ◽  
Author(s):  
Franco A. Taverna ◽  
John Georgiou ◽  
Robert J. McDonald ◽  
Nancy S. Hong ◽  
Alexander Kraev ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Knockout Mice ◽  
Cell Activity ◽  
Long Term Potentiation ◽  
Place Cell ◽  
Term Potentiation ◽  
Nociceptin Receptor

Neurotrophins and Proneurotrophins: Focus on Synaptic Activity and Plasticity in the Brain

2017 ◽  
Vol 23 (6) ◽  
pp. 587-604 ◽  
Author(s):  
Julien Gibon ◽  
Philip A. Barker
Keyword(s):  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Cellular Processes ◽  
Term Potentiation ◽  
Neurotrophin 3 ◽  
New Findings ◽  
The Central Nervous System ◽  
The Brain

Neurotrophins have been intensively studied and have multiple roles in the brain. Neurotrophins are first synthetized as proneurotrophins and then cleaved intracellularly and extracellularly. Increasing evidences demonstrate that proneurotrophins and mature neurotrophins exerts opposing role in the central nervous system. In the present review, we explore the role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) and their respective proform in cellular processes related to learning and memory. We focused on their roles in synaptic activity and plasticity in the brain with an emphasis on long-term potentiation, long-term depression, and basal synaptic transmission in the hippocampus and the temporal lobe area. We also discuss new findings on the role of the Val66Met polymorphism on the BDNF propeptide on synaptic activity.

Long-term potentiation in the hippocampus of fragile X knockout mice

1996 ◽  
Vol 64 (2) ◽  
pp. 246-251 ◽  
Author(s):  
Jean-Marie Godfraind ◽  
Edwin Reyniers ◽  
Kristel De Boulle ◽  
Rudi D'Hooge ◽  
Peter P. De Deyn ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Fragile X ◽  
Long Term Potentiation ◽  
Term Potentiation

Estrogenic Regulation of Synaptic Actin Proteins and Plasticity

2020 ◽  
pp. 69-82
Author(s):  
Enikö A. Kramár
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Synaptic Strength ◽  
Adult Brain ◽  
Actin Dynamics ◽  
Signaling Cascade ◽  
Term Potentiation ◽  
Estrogenic Regulation ◽  
Estradiol Levels

Estrogens are rapid and potent facilitators of synaptic plasticity in the adult brain; however, the steps that link estrogens to factors that regulate synaptic strength remain unclear. The present chapter will first review the acute effects of 17β‎-estradiol on synaptic transmission and long-term potentiation (LTP). It will then describe a synaptic model used to study the substrates of LTP and provide evidence for the ability of estradiol to rapidly engage a selective actin signaling cascade associated with the consolidation of LTP. Finally, it will be shown that chronic reductions in estradiol levels disrupt LTP and actin dynamics but can be reversed by acute infusions of the hormone. It is concluded here that estradiol can promote learning-related plasticity by modifying the synaptic cytoskeleton.

scholarly journals GPR68 deletion impairs hippocampal long-term potentiation and passive avoidance behavior

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yuanyuan Xu ◽  
Mike T. Lin ◽  
Xiang-ming Zha
Keyword(s):  
Passive Avoidance ◽  
Pyramidal Neurons ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Synaptic Cleft ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Metabotropic Receptor ◽  
Term Potentiation

Abstract Increased neural activities reduced pH at the synaptic cleft and interstitial spaces. Recent studies have shown that protons function as a neurotransmitter. However, it remains unclear whether protons signal through a metabotropic receptor to regulate synaptic function. Here, we showed that GPR68, a proton-sensitive GPCR, exhibited wide expression in the hippocampus, with higher expression observed in CA3 pyramidal neurons and dentate granule cells. In organotypic hippocampal slice neurons, ectopically expressed GPR68-GFP was present in dendrites, dendritic spines, and axons. Recordings in hippocampal slices isolated from GPR68−/− mice showed a reduced fiber volley at the Schaffer collateral-CA1 synapses, a reduced long-term potentiation (LTP), but unaltered paired-pulse ratio. In a step-through passive avoidance test, GPR68−/− mice exhibited reduced avoidance to the dark chamber. These findings showed that GPR68 contributes to hippocampal LTP and aversive fear memory.

scholarly journals Pre- and Postnatal Propylthiouracil-Induced Hypothyroidism Impairs Synaptic Transmission and Plasticity in Area CA1 of the Neonatal Rat Hippocampus

Endocrinology ◽  
2003 ◽  
Vol 144 (9) ◽  
pp. 4195-4203 ◽  
Author(s):  
Li Sui ◽  
M. E. Gilbert
Keyword(s):  
Thyroid Hormone ◽  
Synaptic Transmission ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Learning Deficits ◽  
Paired Pulse ◽  
Area Ca1 ◽  
Term Potentiation ◽  
Paired Pulse Depression

Abstract Thyroid hormones are essential for neonatal brain development. It is well established that insufficiency of thyroid hormone during critical periods of development can impair cognitive functions. The mechanisms that underlie learning deficits in hypothyroid animals, however, are not well understood. As impairments in synaptic function are likely to contribute to cognitive deficits, the current study tested whether thyroid hormone insufficiency during development would alter quantitative characteristics of synaptic function in the hippocampus. Developing rats were exposed in utero and postnatally to 0, 3, or 10 ppm propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, administered in the drinking water of dams from gestation d 6 until postnatal day (PN) 30. Excitatory postsynaptic potentials and population spikes were recorded from the stratum radiatum and the pyramidal cell layer, respectively, in area CA1 of hippocampal slices from offspring between PN21 and PN30. Baseline synaptic transmission was evaluated by comparing input-output relationships between groups. Paired-pulse facilitation, paired-pulse depression, long-term potentiation, and long-term depression were recorded to examine short- and long-term synaptic plasticity. PTU reduced thyroid hormones, reduced body weight gain, and delayed eye-opening in a dose-dependent manner. Excitatory synaptic transmission was increased by developmental exposure to PTU. Thyroid hormone insufficiency was also dose-dependently associated with a reduction paired-pulse facilitation and long-term potentiation of the excitatory postsynaptic potential and elimination of paired-pulse depression of the population spike. The results indicate that thyroid hormone insufficiency compromises the functional integrity of synaptic communication in area CA1 of developing rat hippocampus and suggest that these changes may contribute to learning deficits associated with developmental hypothyroidism.

Lipopolysaccharide inhibits induction of long-term potentiation and depression in the rat hippocampal CA1 area

2001 ◽  
Vol 422 (1-3) ◽  
pp. 69-76 ◽  
Author(s):  
Ji-Hoon Jo ◽  
Eun-Jin Park ◽  
Jae-Kwang Lee ◽  
Min-Whan Jung ◽  
Chang-Joong Lee
Keyword(s):  
Long Term Potentiation ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca1 Area ◽  
Ca1 Area

Long-term potentiation enhancing effect of epileptic insult in the CA1 area is dependent on prior-application of primed-burst stimulation

2020 ◽  
Vol 238 (4) ◽  
pp. 897-903
Author(s):  
Masoumeh Gholami ◽  
Narges Hosseinmardi ◽  
Javad Mirnajafi-Zadeh ◽  
Mohamad Javan ◽  
Saeed Semnanian ◽  
...  
Keyword(s):  
Long Term Potentiation ◽  
Burst Stimulation ◽  
Enhancing Effect ◽  
Term Potentiation ◽  
Ca1 Area ◽  
Prior Application
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