LIMK, Cofilin 1 and actin dynamics involvement in fear memory processing

2020 ◽  
Vol 173 ◽  
pp. 107275
Author(s):  
Candela Medina ◽  
Verónica de la Fuente ◽  
Susanne tom Dieck ◽  
Belquis Nassim-Assir ◽  
Tamas Dalmay ◽  
...  
2019 ◽  
Author(s):  
Henry L. Hallock ◽  
Henry M. Quillian ◽  
Kristen R. Maynard ◽  
Yishan Mai ◽  
Huei-Ying Chen ◽  
...  

AbstractAssociating fearful events with the context in which they occur is critical for survival. Dysregulation of context-fear memory processing is a hallmark symptom of several neuropsychiatric disorders, including generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Both the hippocampus and prelimbic subregion (PrL) of the medial prefrontal cortex (mPFC) have been linked with context fear memory recall in rodents, but the mechanisms by which hippocampal-prelimbic circuitry regulates this process remains poorly understood. Spatial and genetic targeting of this circuit in mice allowed us to use molecular profiling to show that hippocampal neurons with projections to the PrL (vHC-PrL projectors) are a transcriptomically-distinct sub-population that is enriched for expression of genes associated with both GAD and PTSD. We further show that stimulation of this population of vHC-PrL projectors suppresses context fear memory recall and impairs the ability of PrL neurons to dynamically distinguish between distinct phases of fear learning. Using transgenic and circuit-specific molecular targeting approaches, we demonstrate that unique patterns of activity-dependent gene transcription within vHC-PrL projectors causally regulate excitatory/inhibitory balance in the PrL during context fear memory recall. Together, our data illuminate the molecular mechanisms by which hippocampal-prelimbic circuitry regulates the retrieval of contextually-mediated fear memories.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Iyo Koyanagi ◽  
Kazuhiro Sonomura ◽  
Toshie Naoi ◽  
Takaaki Ohnishi ◽  
Naoko Kaneko ◽  
...  

AbstractMetabolites underlying brain function and pathology are not as well understood as genes. Here, we applied a novel metabolomics approach to further understand the mechanisms of memory processing in sleep. As hippocampal dentate gyrus neurons are known to consolidate contextual fear memory, we analyzed real-time changes in metabolites in the dentate gyrus in different sleep–wake states in mice. Throughout the study, we consistently detected more than > 200 metabolites. Metabolite profiles changed dramactically upon sleep–wake state transitions, leading to a clear separation of phenotypes between wakefulness and sleep. By contrast, contextual fear memory consolidation induced less obvious metabolite phenotypes. However, changes in purine metabolites were observed upon both sleep–wake state transitions and contextual fear memory consolidation. Dietary supplementation of certain purine metabolites impaired correlations between conditioned fear responses before and after memory consolidation. These results point toward the importance of purine metabolism in fear memory processing during sleep.


2019 ◽  
Author(s):  
Olga I. Ivashkina ◽  
Anna M. Gruzdeva ◽  
Marina A. Roshchina ◽  
Ksenia A. Toropova ◽  
Konstantin V. Anokhin

AbstractThe parietal cortex in rodents has an integrative function and participates in sensory and spatial processing, movement planning and decision-making. However, much less is known about its functions in associative memory processing. Here using Fos immunohistochemical mapping of neuronal activity and two-photon imaging in Fos-eGFP mice we show an involvement of anterior part of the parietal cortex (PtA) in the formation and retrieval of recent fear memory in mice. Using ex vivo c-fos imaging we demonstrate the specific activation of the PtA during recent memory retrieval. In vivo two-photon c-fos imaging confirms these results as well as establishes the activation of the PtA neurons during fear memory formation. Additionally, we describe a design of Fos-Cre-GCaMP transgenic mice to investigate long-term changes of calcium dynamics in neurons captured with Fos-TRAP technique during fear conditioning training.


2022 ◽  
Author(s):  
Wei Sun ◽  
Xiao Chen ◽  
Yazi Mei ◽  
Yang Yang ◽  
Xiaoliang Li ◽  
...  

Fear regulation changes as a function of age and adolescence is a key developmental period for the continued maturation of fear neural circuitry. The involvement of prelimbic proBDNF in fear memory extinction and its mediated signaling were reported previously. Given the inherent high level of proBDNF during juvenile period, we tested whether prelimbic proBDNF regulated synaptic and neuronal functions allowing to influencing retrieval-dependent memory processing. By examining freezing behavior of auditory fear conditioned rats, we found high levels of prelimbic proBDNF in juvenile rats enhanced destabilization of the retrieval-dependent weak but not strong fear memory through activating p75NTR-GluN2B signaling. This modification was attributed to the increment in proportion of thin type spine and promotion in synaptic function, as evidence by facilitation of NMDA-mediated EPSCs and GluN2B-dependent synaptic depression. The strong prelimbic theta- and gamma-oscillation coupling predicted the suppressive effect of proBDNF on the recall of post-retrieval memory. Our results critically emphasize the importance of developmental proBDNF for modification of retrieval-dependent memory and provide a potential critical targeting to inhibit threaten memories associated with neurodevelopment disorders.


2020 ◽  
Author(s):  
Jeong-Kyu Han ◽  
Sun-Ho Kwon ◽  
Yong Gyu Kim ◽  
Jaeyong Choi ◽  
Jong-Il Kim ◽  
...  

Emotional memory processing, such as fear memory, engages a large neuronal network of brain regions including the cerebellum. However, the molecular and cellular mechanisms of the cerebellar cortex modulating the fear memory network is largely unknown. Here, we illustrate a novel mechanism by which synaptic signaling in cerebellar Purkinje cells (PCs) via STAT3 regulates long-term fear memory. Firstly, we generated PC-specific STAT3 knockout (STAT3PKO) mice. Transcriptome analyses revealed that STAT3 deletion results in transcriptional changes that lead to an increase in the expression of glutamate receptors. The amplitude of AMPA receptor-mediated excitatory postsynaptic currents at parallel fiber to PC synapses was larger in STAT3PKO mice than in wild-type littermates. Conditioning at the parallel fiber induced long-term depression of parallel fiber-PC synapses in STAT3PKO mice while the same manipulation induced long-term potentiation in wild-type littermates. Interestingly, STAT3PKO mice showed an aberrantly enhanced long-term fear memory. Neuronal activity in fear-related regions increased in fear-conditioned STAT3PKO mice. Our data suggest that STAT3-dependent molecular regulation in PCs is indispensable for proper expression of fear memory processing.


2021 ◽  
Vol 15 ◽  
Author(s):  
An Buckinx ◽  
Andries Van Schuerbeek ◽  
Jo Bossuyt ◽  
Wissal Allaoui ◽  
Yana Van Den Herrewegen ◽  
...  

Introduction: Single housing of laboratory mice is a common practice to meet experimental needs, or to avoid intermale aggression. However, single housing is considered to negatively affect animal welfare and may compromise the scientific validity of experiments. The aim of this study was to investigate whether the use of a cage with a cage divider, which avoids physical contact between mice while maintaining sensory contact, may be a potential refinement strategy for experiments in which group housing of mice is not possible.Methods: Eight-week-old male C57BL/6JRj mice were single housed, pair housed or pair housed with a cage divider for four (experiment 1) or ten (experiment 2) weeks, after which we performed an open field test, Y-maze spontaneous alternation test, elevated plus maze test, an auditory fear conditioning task, and assessed responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis.Results: Housing conditions did not affect body weight, exploratory activity, anxiety, working memory, fear memory processing or markers for HPA-axis functioning in either experiment 1 or experiment 2. There was an increased distance traveled in mice housed with a cage divider compared to pair housed mice after 4 weeks, and after 10 weeks mice housed with a cage divider made significantly more arm entries in the Y-maze spontaneous alternation test.Conclusion: Taken together, our study did not provide evidence for robust differences in exploratory activity, anxiety, working memory and fear memory processing in male C57BL/6JRj mice that were single housed, pair housed or pair housed with a cage divider.


Author(s):  
Jörg-Tobias Kuhn ◽  
Elena Ise ◽  
Julia Raddatz ◽  
Christin Schwenk ◽  
Christian Dobel

Abstract. Objective: Deficits in basic numerical skills, calculation, and working memory have been found in children with developmental dyscalculia (DD) as well as children with attention-deficit/hyperactivity disorder (ADHD). This paper investigates cognitive profiles of children with DD and/or ADHD symptoms (AS) in a double dissociation design to obtain a better understanding of the comorbidity of DD and ADHD. Method: Children with DD-only (N = 33), AS-only (N = 16), comorbid DD+AS (N = 20), and typically developing controls (TD, N = 40) were assessed on measures of basic numerical processing, calculation, working memory, processing speed, and neurocognitive measures of attention. Results: Children with DD (DD, DD+AS) showed deficits in all basic numerical skills, calculation, working memory, and sustained attention. Children with AS (AS, DD+AS) displayed more selective difficulties in dot enumeration, subtraction, verbal working memory, and processing speed. Also, they generally performed more poorly in neurocognitive measures of attention, especially alertness. Children with DD+AS mostly showed an additive combination of the deficits associated with DD-only and A_Sonly, except for subtraction tasks, in which they were less impaired than expected. Conclusions: DD and AS appear to be related to largely distinct patterns of cognitive deficits, which are present in combination in children with DD+AS.



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