Encoding of Contextual Fear Memory Requires De Novo Proteins in the Prelimbic Cortex

Rizzo, Valerio; Touzani, Khalid; Raveendra, Bindu; Swarnkar, Supriya; Lora, Joan C.; Kadakkuzha, Beena M.; Liu, Xinan; Zhang, Chao; Betel, Doron; Stackman, Robert W.; Puthanveettil, Sathyanarayanan V.

doi:10.1016/j.bpsc.2016.10.002

Cited by 26 publications

(23 citation statements)

References 72 publications

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“…A possible explanation for the absence of anisomycin-induced effects on Test B is the dose of 20 μg/hemisphere used here. The dose range in which this drug produces significant effects when infused into the IL or PL varies from 12.5 to 62.5 μg/hemisphere 15,51,52,55,56 . However, that possibility is unlikely since the same dose interfered with extinction retention (experiment 9), being selected here because it provides more spatially precise protein synthesis inhibition than the dose of 62.5 μg/hemisphere 28 .…”

Section: Discussionmentioning

confidence: 99%

Infralimbic cortex controls fear memory generalization and susceptibility to extinction during consolidation

Bayer

Bertoglio

2020

Sci Rep

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Lesioning or inactivating the infralimbic (IL) subregion of the medial prefrontal cortex before acquisition produces more generalized and extinction-resistant fear memories. However, whether and how it modulates memory specificity and extinction susceptibility while consolidation takes place is still unknown. The present study aims to investigate these questions using muscimol-induced temporary inactivation and anisomycin-induced protein synthesis inhibition in the rat IL following contextual fear conditioning. Results indicate that the IL activity immediately after acquisition, but not six hours later, controls memory generalization over a week, regardless of its strength. Such IL function depends on the context-shock pairing since muscimol induced no changes in animals exposed to immediate shocks or the conditioning context only. Animals in which the IL was inactivated during consolidation extinguished similarly to controls within the session but were unable to recall the extinction memory the following day. Noteworthy, these post-acquisition IL inactivation-induced effects were not associated with changes in anxiety, as assessed in the elevated plus-maze test. Anisomycin results indicate that the IL protein synthesis during consolidation contributes more to producing extinction-sensitive fear memories than memory specificity. Collectively, present results provide evidence for the IL's role in controlling generalization and susceptibility to extinction during fear memory consolidation.

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Section: Discussionmentioning

confidence: 99%

Infralimbic cortex controls fear memory generalization and susceptibility to extinction during consolidation

Bayer

Bertoglio

2020

Sci Rep

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“…CFC was performed as previously described ( Rizzo et al, 2017 ). Briefly, experiments were performed using a set of four modified Noldus PhenoTyper (Model 3000) chambers (Leesburg, VA) with shock floors ( Burgos-Robles et al, 2009 ).…”

Section: Methodsmentioning

confidence: 99%

Molecular motor protein KIF5C mediates structural plasticity and long-term memory by constraining local translation

et al. 2021

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Synaptic structural plasticity, key to long-term memory storage, requires translation of localized RNAs delivered by long-distance transport from the neuronal cell body. Mechanisms and regulation of this system remain elusive. Here, we explore the roles of KIF5C and KIF3A, two members of kinesin superfamily of molecular motors (Kifs), and find that loss of function of either kinesin decreases dendritic arborization and spine density whereas gain of function of KIF5C enhances it. KIF5C function is a rate-determining component of local translation and is associated with $650 RNAs, including EIF3G, a regulator of translation initiation, and plasticity-associated RNAs. Loss of function of KIF5C in dorsal hippocampal CA1 neurons constrains both spatial and contextual fear memory, whereas gain of function specifically enhances spatial memory and extinction of contextual fear. KIF5C-mediated long-distance transport of local translation substrates proves a key mechanism underlying structural plasticity and memory.

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“…Because T22 neutralization rescued novel object learning but did not rescue fear response, results from fear response studies, taken together with the open-field results that hinted abnormal anxiety in T22 mice, suggest that multiple amyloid and tau protein species, compositions (e.g., monomers, dimers, etc. ), and affected brain regions are involved in the complex fear behavior (41)(42)(43). Thus, infection elicited amyloid and tau protein species that contribute to fear impairment.…”

Section: Endothelium-derived Amyloid and Tau Proteins Impair Fear Resmentioning

confidence: 99%

Infection‐induced endothelial amyloids impair memory

et al. 2019

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Patients with nosocomial pneumonia exhibit elevated levels of neurotoxic amyloid and tau proteins in the cerebrospinal fluid (CSF). In vitro studies indicate that pulmonary endothelium infected with clinical isolates of either Pseudomonas aeruginosa, Klebsiella pneumoniae, or Staphylococcus aureus produces and releases cytotoxic amyloid and tau proteins. However, the effects of the pulmonary endothelium‐derived amyloid and tau proteins on brain function have not been elucidated. Here, we show that P. aeruginosa infection elicits accumulation of detergent insoluble tau protein in the mouse brain and inhibits synaptic plasticity. Mice receiving endothelium‐derived amyloid and tau proteins via intracerebroventricular injection exhibit a learning and memory deficit in object recognition, fear conditioning, and Morris water maze studies. We compared endothelial supernatants obtained after the endothelia were infected with P. aeruginosa possessing an intact [P. aeruginosa isolated from patient 103 (PA103) supernatant] or defective [mutant strain of P. aeruginosa lacking a functional type 3 secretion system needle tip complex (ΔPcrV) supernatant] type 3 secretion system. Whereas the PA103 supernatant impaired working memory, the ΔPcrV supernatant had no effect. Immunodepleting amyloid or tau proteins from the PA103 supernatant with the A11 or T22 antibodies, respectively, overtly rescued working memory. Recordings from hippocampal slices treated with endothelial supernatants or CSF from patients with or without nosocomial pneumonia indicated that endothelium‐derived neurotoxins disrupted the postsynaptic synaptic response. Taken together, these results establish a plausible mechanism for the neurologic sequelae consequent to nosocomial bacterial pneumonia.—Balczon, R., Pittet, J.‐F., Wagener, B. M., Moser, S. A., Voth, S., Vorhees, C. V., Williams, M. T., Bridges, J. P., Alvarez, D. F., Koloteva, A., Xu, Y., Zha, X.‐M., Audia, J. P., Stevens, T., Lin, M. T. Infection‐induced endothelial amyloids impair memory. FASEB J. 33, 10300–10314 (2019). http://www.fasebj.org

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Encoding of Contextual Fear Memory Requires De Novo Proteins in the Prelimbic Cortex

Cited by 26 publications

References 72 publications

Infralimbic cortex controls fear memory generalization and susceptibility to extinction during consolidation

Infralimbic cortex controls fear memory generalization and susceptibility to extinction during consolidation

Molecular motor protein KIF5C mediates structural plasticity and long-term memory by constraining local translation

Infection‐induced endothelial amyloids impair memory

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