Dorsal Hippocampus to Infralimbic Cortex Circuit is Essential for the Recall of Extinction Memory

2020 ◽  
Author(s):  
Cheng Qin ◽  
Xin-Lan Bian ◽  
Hai-Yin Wu ◽  
Jia-Yun Xian ◽  
Cheng-Yun Cai ◽  
...  
Keyword(s):  
Memory Impairment ◽  
Stress Disorder ◽  
Dorsal Hippocampus ◽  
Neural Mechanisms ◽  
Male Mice ◽  
Infralimbic Cortex ◽  
Extracellular Signal Regulated Kinase ◽  
Conditional Deletion ◽  
Extracellular Signal ◽  
Extinction Memory

Abstract Posttraumatic stress disorder subjects usually show impaired recall of extinction memory, leading to extinguished fear relapses. However, little is known about the neural mechanisms underlying the impaired recall of extinction memory. We show here that the activity of dorsal hippocampus (dHPC) to infralimbic (IL) cortex circuit is essential for the recall of fear extinction memory in male mice. There were functional neural projections from the dHPC to IL. Using optogenetic manipulations, we observed that silencing the activity of dHPC-IL circuit inhibited recall of extinction memory while stimulating the activity of dHPC-IL circuit facilitated recall of extinction memory. “Impairment of extinction consolidation caused by” conditional deletion of extracellular signal-regulated kinase 2 (ERK2) in the IL prevented the dHPC-IL circuit-mediated recall of extinction memory. Moreover, silencing the dHPC-IL circuit abolished the effect of intra-IL microinjection of ERK enhancer on the recall of extinction memory. Together, we identify a dHPC to IL circuit that mediates the recall of extinction memory, and our data suggest that the dysfunction of dHPC-IL circuit and/or impaired extinction consolidation may contribute to extinguished fear relapses.

scholarly journals Inducible and Conditional Deletion of Extracellular Signal-regulated Kinase 5 Disrupts Adult Hippocampal Neurogenesis

2012 ◽  
Vol 287 (28) ◽  
pp. 23306-23317 ◽  
Author(s):  
Yung-Wei Pan ◽  
Junhui Zou ◽  
Wenbin Wang ◽  
Hiroyuki Sakagami ◽  
Michael G. Garelick ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Extracellular Signal Regulated Kinase ◽  
Conditional Deletion ◽  
Extracellular Signal

scholarly journals Hydrophilic Glycoproteins of an Edible Green Alga Capsosiphon fulvescens Prevent Aging-Induced Spatial Memory Impairment by Suppressing GSK-3β-Mediated ER Stress in Dorsal Hippocampus

Marine Drugs ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 168 ◽  
Author(s):  
Jeong Oh ◽  
Taek-Jeong Nam
Keyword(s):  
Oral Administration ◽  
Spatial Memory ◽  
Er Stress ◽  
Cognitive Dysfunction ◽  
Memory Impairment ◽  
Glycogen Synthase ◽  
Dorsal Hippocampus ◽  
Extracellular Signal ◽  
Capsosiphon Fulvescens ◽  
Gsk 3Β

Endoplasmic reticulum (ER) stress is involved in various neurodegenerative disorders. We previously found that Capsosiphon fulvescens (C. fulvescens) crude proteins enhance spatial memory by increasing the expression of brain-derived neurotrophic factor (BDNF) in rat dorsal hippocampus. The present study investigated whether the chronic oral administration of hydrophilic C. fulvescens glycoproteins (Cf-hGP) reduces aging-induced cognitive dysfunction by regulating ER stress in the dorsal hippocampus. The oral administration of Cf-hGP (15 mg/kg/day) for four weeks attenuated the aging-induced increase in ER stress response protein glucose-regulated protein 78 (GRP78) in the synaptosome of the dorsal hippocampus; this was attenuated by the function-blocking anti-BDNF antibody (1 μg/μL) and a matrix metallopeptidase 9 inhibitor 1 (5 μM). Aging-induced GRP78 expression was associated with glycogen synthase kinase-3 beta (GSK-3β) (Tyr216)-mediated c-Jun N-terminal kinase phosphorylation, which was downregulated upon Cf-hGP administration. The Cf-hGP-induced increase in GSK-3β (Ser9) phosphorylation was downregulated by inhibiting tyrosine receptor kinase B and extracellular signal-regulated kinase (ERK)1/2 with cyclotraxin-B (200 nM) and SL327 (10 μM), respectively. Cf-hGP administration or the inhibition of ER stress with salubrinal (1 mg/kg, i.p.) significantly decreased aging-induced spatial memory impairment. These findings suggest that the activation of the synaptosomal BDNF-ERK1/2 signaling in the dorsal hippocampus by Cf-hGP attenuates age-dependent ER stress-induced cognitive dysfunction.

scholarly journals Activation of unliganded FGF receptor by extracellular phosphate potentiates proteolytic protection of FGF23 by its O-glycosylation

2019 ◽  
Vol 116 (23) ◽  
pp. 11418-11427 ◽  
Author(s):  
Yuichi Takashi ◽  
Hidetaka Kosako ◽  
Shun Sawatsubashi ◽  
Yuka Kinoshita ◽  
Nobuaki Ito ◽  
...  
Keyword(s):  
Serum Phosphate ◽  
Pi Control ◽  
Erk Pathway ◽  
Fgf Receptor ◽  
Extracellular Signal Regulated Kinase ◽  
Conditional Deletion ◽  
Extracellular Signal ◽  
Control Serum ◽  
Fgf 23 ◽  
Umr 106

Fibroblast growth factor (FGF) 23 produced by bone is a hormone that decreases serum phosphate (Pi). Reflecting its central role in Pi control, serum FGF23 is tightly regulated by serum Pi alterations. FGF23 levels are regulated by the transcriptional event and posttranslational cleavage into inactive fragments before its secretion. For the latter, O-glycosylation of FGF23 by GALNT3 gene product prevents the cleavage, leading to an increase in serum FGF23. However, the molecular basis of Pi sensing in the regulation of serum FGF23 remains elusive. In this study, we showed that high Pi diet enhanced the skeletal expression of Galnt3, but not Fgf23, with expected increases in serum FGF23 and Pi in mice. Galnt3 induction by high Pi was further observed in osteoblastic UMR 106 cells, and this was mediated by activation of the extracellular signal-regulated kinase (ERK) pathway. Through proteomic searches for the upstream sensor for high Pi, we identified one subtype of the FGF receptor (FGFR1c), which was phosphorylated by high Pi in the absence of FGFs. The mode of unliganded FGFR activation by high Pi appeared different from that of FGFR bound to a canonical FGFR ligand (FGF2) when phosphorylation of the FGFR substrate 2α and ERK was monitored. Finally, we showed that an FGFR inhibitor and conditional deletion of Fgfr1 in osteoblasts/osteocytes abrogated high Pi diet-induced increases in serum FGF23 and femoral Galnt3 expression in mice. Thus, these findings uncover an unrecognized facet of unliganded FGFR function and illustrate a Pi-sensing pathway involved in regulation of FGF23 production.

scholarly journals Dynamic Changes of Cytoskeleton-Related Proteins Within Reward-Related Brain Regions in Morphine-Associated Memory

2021 ◽  
Vol 14 ◽  
Author(s):  
Xixi Yang ◽  
Yichong Wen ◽  
Yuxiang Zhang ◽  
Feifei Gao ◽  
Jingsi Yang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Dorsal Hippocampus ◽  
Brain Regions ◽  
Protein Activity ◽  
Dynamic Changes ◽  
Drug Induced ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Related Proteins

Drug-induced memory engages complex and dynamic processes and is coordinated at multiple reward-related brain regions. The spatiotemporal molecular mechanisms underlying different addiction phases remain unknown. We investigated the role of β-actin, as well as its potential modulatory protein activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) and extracellular signal-regulated kinase (ERK), in reward-related associative learning and memory using morphine-induced conditioned place preference (CPP) in mice. CPP was established by alternate morphine (10 mg/kg) injections and extinguished after a 10-day extinction training, while the withdrawal group failed to extinguish without training. In the nucleus accumbens (NAc), morphine enhanced the level of β-actin and Arc only during extinction, while p-ERK1/2 was increased during both CPP acquisition and extinction phases. In the dorsal hippocampus, morphine induced an upregulation of p-ERK only during extinction, while p-β-actin was elevated during both CPP establishment and extinction. In the dorsal hippocampus, Arc was elevated during CPP formation and suppressed during extinction. Compared with the NAc and dorsal hippocampus, dynamic changes in the medial prefrontal cortex (mPFC) and caudate putamen (CPu) were not very significant. These results suggested region-specific changes of p-β-actin, Arc/Arg3.1, and p-ERK1/2 protein during establishment and extinction phases of morphine-induced CPP. These findings unveiled a spatiotemporal molecular regulation in opiate-induced plasticity.

scholarly journals Dorsal Hippocampus ERK2 Signaling Mediates Anxiolytic-Related Behavior in Male Rats

2019 ◽  
Vol 3 ◽  
pp. 247054701989703
Author(s):  
Jorge A. Sierra-Fonseca ◽  
Lyonna F. Parise ◽  
Francisco J. Flores-Ramirez ◽  
Eden H. Robles ◽  
Israel Garcia-Carachure ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Open Field ◽  
Field Test ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Dorsal Hippocampus ◽  
Male Rats ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Plus Maze

Background Anxiety disorders are the most common neuropathologies worldwide, but the precise neuronal mechanisms that underlie these disorders remain unknown. The hippocampus plays a role in mediating anxiety-related responses, which can be modeled in rodents using behavioral assays, such as the elevated plus maze. Yet, the molecular markers that underlie affect-related behavior on the elevated plus maze are not well understood. Methods We used herpes simplex virus vector delivery to overexpress extracellular signal-regulated kinase-2, a signaling molecule known to be involved in depression and anxiety, within the dorsal hippocampus of adult Sprague-Dawley male rats. Three days post virus delivery, we assessed anxiety-like responses on the elevated plus maze or general locomotor activity on the open field test. Results When compared to controls, rats overexpressing extracellular signal-regulated kinase-2 in the dorsal hippocampus displayed an anxiolytic-like phenotype, per increases in time spent in the open arms, and less time in the closed arms, of the elevated plus maze. Furthermore, no changes in locomotor activity as a function of virus infusion were observed on the open field test between the experimental groups. Conclusion This investigation demonstrates that virus-mediated increases of extracellular signal-regulated kinase-2 signaling, within the hippocampus, plays a critical role in decreasing anxiogenic responses on the rat elevated plus maze. As such, our data provide construct validity, at least in part, to the molecular mechanisms that mediate anxiolytic-like behavior in rodent models for the study of anxiety.

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