Understanding the contributions of visual stimuli to contextual fear conditioning: a proof-of-concept study using LCD screens

Mapping Intimacies ◽

10.1101/069781 ◽

2016 ◽

Author(s):

Nathen J. Murawski ◽

Arun Asok

Keyword(s):

Fear Conditioning ◽

Visual Information ◽

Visual Image ◽

Contextual Fear Conditioning ◽

Fear Learning ◽

Proof Of Concept ◽

Facilitation Effect ◽

Simple Modification ◽

Conditioning Paradigm ◽

Contextual Fear

AbstractThe precise contribution of visual information to contextual fear-learning and discrimination has remained elusive. To better understand this contribution, we coupled the context pre-exposure facilitation effect (CPFE) fear conditioning paradigm with presentations of distinct visual scenes displayed on 4 LCD screens surrounding a conditioning chamber. Adult male Long-Evans rats received non-reinforced context pre-exposure on Day 1, an immediate 1.5 mA foot shock on Day 2, and a non-reinforced context test on Day 3. Rats were pre-exposed to either digital Context (dCtx) A, dCtx B, a distinct Context C, or no context on Day 1. Context A and B were identical except for the visual image displayed on the LCD monitors. Immediate shock and retention testing occurred in dCtx A. Rats pre-exposed dCtx A showed the CPFE with significantly higher levels of freezing compared to learning controls. Rats pre-exposed to Context B failed to show the CPFE, with freezing that did not differ significantly from any group. The results suggest that 1) visual information contributes to contextual fear learning in rats and that 2) visual components of the context can be parametrically controlled via LCD screens. Our approach offers a simple modification to contextual fear conditioning whereby the visual features of a context can be precisely controlled to better understand how rodents discriminate and generalize fear across environments.

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Changes in protein kinase C (PKC) activity, isozyme translocation, and GAP-43 phosphorylation in the rat hippocampal formation after a single-trial contextual fear conditioning paradigm

Hippocampus ◽

10.1002/hipo.10015 ◽

2002 ◽

Vol 12 (4) ◽

pp. 457-464 ◽

Cited By ~ 40

Author(s):

Elizabeth Young ◽

Teresa Cesena ◽

Karina F. Meiri ◽

Nora I. Perrone-Bizzozero

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Fear Conditioning ◽

Hippocampal Formation ◽

Contextual Fear Conditioning ◽

Single Trial ◽

Conditioning Paradigm ◽

Contextual Fear ◽

Kinase C

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Translating Memories

Science Signaling ◽

10.1126/scisignal.2004279 ◽

2013 ◽

Vol 6 (273) ◽

pp. ec94-ec94 ◽

Cited By ~ 3

Author(s):

Nancy R. Gough

Keyword(s):

Fear Conditioning ◽

Hippocampal Slices ◽

Contextual Fear Conditioning ◽

Synaptic Activity ◽

Wild Type ◽

Conditioning Paradigm ◽

Contextual Fear ◽

Activity Dependent ◽

New Protein

The cellular model of memory is a synaptic plasticity event called long-term potentiation (LTP). LTP can be divided into two phases: The early phase (E-LTP) lasts less than 2 hours and does not require new protein synthesis, and the late phase (L-LTP) can last many hours and requires new protein synthesis. Translation of mRNAs is regulated through various mechanisms, one of which is the binding of poly(A)-binding protein (PABP) to the poly(A) tail of the target mRNA. PAIP2A and PAIP2B (PAIP-interacting protein 2A and 2B) inhibit translation by interfering with PABP function. Khoutorsky et al. found that degradation of PAIP2A, which is the form that is abundant in the brain, linked synaptic activity to enhanced translation and contributed to learning and memory in mice. Hippocampal slices from Paip2a–/– mice showed L-LTP in response to a stimulus that only triggered E-LTP in slices from wild-type mice and showed impaired L-LTP in response to a stimulus that triggered L-LTP in slices from wild-type mice. Consistent with these electrophysiological studies, behavorial memory tests indicated that Paip2a–/– mice showed faster learning in spatial long-term memory tests in response to weak training but showed impaired learning in response to a long-term contextual fear conditioning test that used a strong training paradigm. Experiments with cultured neurons and hippocampal slices showed an activity-dependent decrease in the abundance of PAIP2A that could be prevented by pharmacological inhibition of the calcium-dependent proteases calpains. The calpain-dependent reduction in PAIP2A was also detected in mice subjected to the contextual fear conditioning paradigm, and infusion of calpain inhibitors impaired long-term contextual fear memory. Increased production of calcium-calmodulin kinase IIα (CaMKIIα) occurs in response to synaptic activity and is necessary for learning. The abundance of CaMKIIα in the hippocampus was increased in Paip2a–/– mice trained in a contextual fear conditioning paradigm compared with untrained mice or wild-type trained mice. This increase in CaMKIIα resulted from increased translation because CaMKIIα mRNA was shifted to heavy polysome fractions in the brains of Paip2a–/– trained mice and the association of PABP with this mRNA was greatest in the Paip2a–/– trained mice. Thus, activity-dependent degradation of a translation inhibitor contributes to the enhanced translation needed for learning and memory.A. Khoutorsky, A, Yanagiya, C. G. Gkogkas, M. R. Fabian, M. Prager-Khoutorsky, R. Cao, K. Gamache, F. Bouthiette, A. Parsyan, R. E. Sorge, J. S. Mogil, K. Nader, J.-C. Lacaille, N. Sonenberg, Control of synaptic plasticity and memory via suppression of poly(A)-binding protein. Neuron78, 298–311 (2013). [Online Journal]

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Contextual Fear Conditioning in Zebrafish

10.1101/068833 ◽

2016 ◽

Author(s):

Justin W. Kenney ◽

Ian C. Scott ◽

Sheena A. Josselyn ◽

Paul W. Frankland

Keyword(s):

Fear Conditioning ◽

Learning And Memory ◽

Molecular Basis ◽

Aversive Stimulus ◽

Genetic Manipulation ◽

Contextual Fear Conditioning ◽

Conditioning Paradigm ◽

Contextual Fear ◽

Extinction Rates ◽

Made In

AbstractZebrafish are a genetically tractable vertebrate that hold considerable promise for elucidating the molecular basis of behavior. Although numerous recent advances have been made in the ability to precisely manipulate the zebrafish genome, much less is known about many aspects learning and memory in adult fish. Here, we develop a contextual fear conditioning paradigm using an electric shock as the aversive stimulus. We find that contextual fear conditioning is modulated by shock intensity, prevented by inhibition of (N-methyl-D-aspartate) NMDA receptors, lasts at least 14 days, and exhibits extinction. Furthermore, fish of various background strains (AB, Tu, and TL) are able to acquire fear conditioning, but differ in fear extinction rates. Taken together, we find that contextual fear conditioning in zebrafish shares many similarities with the widely used contextual fear conditioning paradigm in rodents. Combined with the amenability of genetic manipulation in zebrafish, we anticipate that our paradigm will prove to be a useful complementary system in which to examine the molecular basis of vertebrate learning and memory.

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Network supporting contextual fear learning after dorsal hippocampal damage has increased dependence on retrosplenial cortex

10.1101/209866 ◽

2017 ◽

Author(s):

Cesar A.O. Coelho ◽

Tatiana L. Ferreira ◽

Juliana C.K. Soares ◽

João R. Sato ◽

Maria Gabriela M. Oliveira

Keyword(s):

Fear Conditioning ◽

Correlation Coefficients ◽

Brain Regions ◽

Memory System ◽

Retrosplenial Cortex ◽

Contextual Fear Conditioning ◽

Fear Learning ◽

Hippocampal Damage ◽

Contextual Fear ◽

Dorsal Hippocampal

ABSTRACTHippocampal damage results in profound retrograde, but no anterograde amnesia in contextual fear conditioning (CFC). Although the content learned in the latter have been discussed, the compensating regions were seldom proposed and never empirically addressed. Here, we employed network analysis of pCREB expression quantified from brain slices of rats with dorsal hippocampal lesion (dHPC) after undergoing CFC session. Using inter-regional correlations of pCREB-positive nuclei between brain regions, we modelled functional networks using different thresholds. The dHPC network showed small-world topology, equivalent to SHAM (control) network. However, diverging hubs were identified in each network. In a direct comparison, hubs in both networks showed consistently higher centrality values compared to the other network. Further, the distribution of correlation coefficients was different between the groups, with most significantly stronger correlation coefficients belonging to the SHAM network. These results suggest that dHPC network engaged in CFC learning is partially different, and engage alternative hubs. We next tested if pre-training lesions of dHPC and one of the new dHPC network hubs (perirhinal, Per; or disgranular retrosplenial, RSC, cortices) would impair CFC. Only dHPC-RSC, but not dHPC-Per, impaired CFC. Interestingly, only RSC showed a consistently higher centrality in the dHPC network, suggesting that the increased centrality reflects an increased functional dependence on RSC. Our results provide evidence that, without hippocampus, the RSC, an anatomically central region in the medial temporal lobe memory system might support CFC learning and memory.AUTHOR SUMMARYWhen determined cognitive performances are not affected by brain lesions of regions generally involved in that performance, the interpretation is that the remaining regions can compensate the damaged one. In contextual fear conditioning, a memory model largely used in laboratory rodents, hippocampal lesions produce amnesia for events occurred before, but not after the lesion, although the hippocampus is known to be important for new learning. Addressing compensation in animal models has always been challenging as it requires large-scale brain mapping. Here, we quantified 30 brain regions and used mathematical tools to model how a brain network can compensate hippocampal loss and learn contextual fear. We described that the damaged network preserved general interactivity characteristics, although different brain regions were identified as highly important for the network (e.g. highly connected). Further, we empirically validated our network model by performing double lesions of the hippocampus and the alternative hubs observed in the network models. We verified that double lesion of the hippocampus and retrosplenial cortex, one of the hubs, impaired contextual fear learning. We provide evidence that without hippocampus, the remaining network relies on alternative important regions from the memory system to coordinate contextual fear learning.

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