Conditioned contextual fear memory to assess natural forgetting and cognitive enhancement in rats

Main Article Content

Sven RM Schuette
Scott Hobson

Keywords

contextual fear conditioning, memory enhancement, memory acquisition, hippocampus

Abstract

Aversively established contextual fear memory manifests itself in robust freezing behavior, often lasting several weeks or months. Therefore, this approach is amenable to investigate the underlying neural circuitries by lesion or inactivation of specific brain regions or to test efficacy of substances that disrupt either the ability to acquire the association or to retrieve memories. In contrast, investigation of memory enhancement using this technique is time intensive since the non-treated control group naturally forgets the learned association only weeks after acquisition. Pharmacological interventions have been used to overcome this time span by disrupting memory at any time point, however, limiting it a mechanistic model of reversal of impairments instead of studying memory enhancement. Here, we investigated several parameters of the cued and contextual fear conditioning (CFC) protocol such that, while memory acquisition is established, loss of fear association occurs within a shorter time frame, allowing studies of memory enhancement in the context of natural forgetting. We found that three predictive tone-cues, each separated from a 0.3 mA foot shock by an interstimulus interval of 2 s and a pre-exposure to the context enables the investigation of enhanced contextual memory 7 d post training without the necessity of inducing pharmacological lesions.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...
Abstract 36 | HTML Downloads 248 PDF Downloads 141 Supplementary information Downloads 0

References

1. Bolles RC. Species-specific defence reactions and avoidance learning. Psychol Rev. 1970;77(1):32–48.
2. Fanselow MS. What is conditioned fear? Trends Neurosci. 1984 Dec;7(12):460–2.
3. Crawford M, Masterson FA. Species-specific defense reactions and avoidance learning. An evaluative review. Pavlov J Biol Sci. 1982;17(4):204–14.
4. Frankland PW, Bontempi B, Talton LE, Kaczmarek L, Silva AJ. The involvement of the anterior cingulate cortex in remote contextual fear memory. Science. 2004 May 7;304(5672):881–3.
5. Chowdhury N, Quinn JJ, Fanselow MS. Dorsal hippocampus involvement in trace fear conditioning with long, but not short, trace intervals in mice. Behav Neurosci. 2005;119(5):1396–402.
6. Quinn JJ, Ma QD, Tinsley MR, Koch C, Fanselow MS. Inverse temporal contributions of the dorsal hippocampus and medial prefrontal cortex to the expression of long-term fear memories. Learn Mem. 2008;15(5):368–72.
7. Curzon P, Rustay NR, Browman KE. Chapter 2 Cued and Contextual Fear Conditioning for Rodents. In: Buccafusco J, editor. Methods of Behavior Analysis in Neuroscience. 2nd ed. CRC Press/Taylor & Francis; 2009. p. 1–11.
8. Kim JJ, Fanselow MS. Modality-specific retrograde amnesia of fear. Science. 1992 May 1;256(5057):675–7.
9. Maren S, Aharonov G, Fanselow MS. Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats. Behav Brain Res. 1997;88(2):261–74.
10. Wiltgen BJ, Silva AJ. Memory for context becomes less specific with time. Learn Mem. 2007;14:313–7.
11. Phillips RG, LeDoux JE. Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci. 1992;106(2):274–85.
12. LeDoux JE. Emotion: clues from the brain. Annu Rev Psychol. 1995;46:209–35.
13. Helmstetter FJ, Bellgowan PS. Effects of muscimol applied to the basolateral amygdala on acquisition and expression of contextual fear conditioning in rats. Behav Neurosci. 1994 Oct;108(5):1005–9.
14. Muller J, Corodimas KP, Fridel Z, LeDoux JE. Functional inactivation of the lateral and basal nuclei of the amygdala by muscimol infusion prevents fear conditioning to an explicit conditioned stimulus and to contextual stimuli. Behav Neurosci. 1997 Aug;111(4):683–91.
15. Bast T, Zhang WN, Feldon J. Dorsal hippocampus and classical fear conditioning to tone and context in rats: Effects of local NMDA-receptor blockade and stimulation. Hippocampus. 2003;13(6):657–75.
16. Balogh SA, Radcliffe RA, Logue SF, Wehner JM. Contextual and cued fear conditioning in C57BL/6J and DBA/2J mice: context discrimination and the effects of retention interval. Behav Neurosci. 2002;116(6):947–57.
17. Biedenkapp JC, Rudy JW. Context preexposure prevents forgetting of a contextual fear memory: implication for regional changes in brain activation patterns associated with recent and remote memory tests. Learn Mem. 2007;14(3):200–3.
18. Einarsson EÖ, Pors J, Nader K. Systems Reconsolidation Reveals a Selective Role for the Anterior Cingulate Cortex in Generalized Contextual Fear Memory Expression. Neuropsychopharmacology. 2015;40(August):480–7.
19. Blanchard RJ, Fukunaga KK, Blanchard DC. Environmental control of defensive reactions to footshock. Bull Psychon Soc. 1976 Sep 8;8(2):129–30.
20. Fanselow MS. Associative vs topographical accounts of the immediate shock-freezing deficit in rats: Implications for the response selection rules governing species-specific defensive reactions. Learn Motiv. 1986;17(1):16–39.
21. Rudy JW, O’Reilly RC. Contextual fear conditioning, conjunctive representations, pattern completion, and the hippocampus. Behav Neurosci. 1999;113(5):867–80.
22. Bae SE, Holmes NM, Westbrook RF. False context fear memory in rats. Learn Mem. 2015;22(10):519–25.
23. Jasnow AM, Lynch JF, Gilman TL, Riccio DC. Perspectives on fear generalization and its implications for emotional disorders. J Neurosci Res. 2017;95(3):821–35.
24. Parent MB, Quirarte GL, Cahill L, McGaugh JL. Spared retention of inhibitory avoidance learning after posttraining amygdala lesions. Behav Neurosci. 1995;109(4):803–7.
25. Crestani F, Keist R, Fritschy J-M, Benke D, Vogt K, Prut L, et al. Trace fear conditioning involves hippocampal α5 GABAA receptors. Proc Natl Acad Sci U S A. 2002;99(13):8980–5.
26. Bangasser DA. Trace Conditioning and the Hippocampus: The Importance of Contiguity. J Neurosci. 2006;26(34):8702–6.
27. Marlin NA. Contextual associations in trace conditioning. Anim Learn Behav. 1981;9(4):519–23.
28. Selden NR, Everitt BJ, Jarrard LE, Robbins TW. Complementary roles for the amygdala and hippocampus in aversive conditioning to explicit and contextual cues. Neuroscience. 1991;42(2):335–50.
29. Gilmartin MR, Helmstetter FJ. Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex. Learn Mem. 2010;17(6):289–96.
30. Schuette SRM, Fernández-Fernández D, Lamla T, Rosenbrock H, Hobson S. Overexpression of Protein Kinase Mζ in the Hippocampus Enhances Long-Term Potentiation and Long-Term Contextual But Not Cued Fear Memory in Rats. J Neurosci. 2016;36(15):4313–24.