Extinction of Contextual Fear with Timed Exposure to Enriched Environment: A Differential Effect

Abstract

Background: Extinction of fear memory depends on the environmental and emotional cues. Furthermore, consolidation of extinction is also dependent on the environmental exposure. But, the relationship of the time of the exposure to a variety of environmental cues is not well known. The important region involved in facilitation of extinction of fear memory is through diversion of the flow of information leaving the lateral nucleus of amygdala. Purpose: The study aimed to address a question to explain how these brain regions react to environmental stimulation during the retention and extinction of fear memory. Methods: An enriched environment (EE) is assumed to mediate extinction of fear memory, we examined the apparent discrepancy between the effects of defensive response, the freezing behavior induced by Pavlovian classical fear conditioning by subjecting them to variance in the timing to EE. The different timing of EE exposure was 10 days of EE either before fear conditioning and/or after extinction training to the rats. The local field potentials was recorded from CA1 hippocampus, lateral nucleus of amygdala and infralimbic region of medial prefrontal cortex (mPFC) during the fear learning and extinction from the control rats and rats exposed to EE before and after fear conditioning. Results: Exposure to EE before the fear conditioning and after extinction training was more effective in the extinction fear memory. In addition, we also found switching from exploratory locomotion to freezing during retention of contextual fear memory which was associated with decreased theta power and reduced synchronized theta oscillations in CA1-hippocampus, lateral nucleus of amygdala, and infralimbic region of mPFC. Conclusion: Thus, we propose that the timing of exposure to EE play a key role in the extinction of fear memory.

The systemic effects of the enriched environment on the conditioned fear reaction

“…Moreover, the freezing time in rats of the STAND group, in contrast to the animals of the EE group, was approximately the same in the neutral and “dangerous” contexts. Similar data was obtained by Hegde et al (2017) . In their experiments, the rats were trained for CFR in the context of chamber 1, and CFR was tested in the other, albeit very similar context, chamber 2.…”

“…According to our hypothesis, the animals housed in the EE should extinguish the CFR faster than the animals housed in the STAND environment. This was confirmed in many experiments (Hunter, 2015;Lach et al, 2016;Hegde et al, 2017;Cavalcante et al, 2020;on others). In particular, Lach et al (2016) showed that the extinction of CFR in context occurs faster in rats housed in the EE (2 weeks) compared to the STAND group.…”

“…The degree and strength of these associations depend on the magnitude and number of CS and US pairings, and the loads and presentations of environmental stimuli. With regard to the effects of EE on the CFR, many factors should be taken into account, such as the duration of staying in the EE, the age of the animal from which EE is started, features of the EE procedure (for example, its application before the onset of stress or after it); the character of the assessment tests and models used ( Clemenson et al, 2015 ; Hegde et al, 2017 ; Cavalcante, 2019 ; O’Leary et al, 2019 ; Cavalcante et al, 2020 ; Cheng S. T. et al, 2022 ) and so on. Of particular interest is the effect of EE on the developing brain.…”

Hippocampal Administration of Levothyroxine Impairs Contextual Fear Memory Consolidation in Rats

“…Limbic regions including hippocampus and amygdala are involved in the circuitry of contextual fear conditioning (Phillips and LeDoux, 1992 ; Fang et al, 2017 ; Hegde et al, 2017 ) and sensitive to hormonal alterations. THs receptors are rich in both hippocampus and amygdala (Puymirat et al, 1991 ; Desouza et al, 2005 ; Singh et al, 2016 ).…”