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

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.

Neonatal administration of a subanaesthetic dose of JM-1232(−) in mice results in no behavioural deficits in adulthood

“…To assess associative memory, they were also tested for contextual/cued fear conditioning. Fear conditioning is a classical pavlovian model to assess associative memory for the pairing of a neutral CS (tone-cue) and the context with an aversive US (electric foot shock) 30 . Once this pairing is acquired, either the context or the tone-cue alone induces the conditioned reaction, i.e.…”

“…The fear-conditioning test assess associative memory 30 and was performed as previously described 49 . Briefly, the conditioning trial for contextual and cued fear conditioning consisted of a 5-min exploration period followed by three conditioned stimulus-unconditioned stimulus pairings (CS-US), each separated by a 1 min intertrial interval (US: 1 mA foot shock intensity, 1 s duration; CS: 80 db white noise, 20 s duration; US was delivered during the last seconds of CS presentation).…”

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“…It is important to note that most neurobiological studies employ simple temporal pairings of CS and US to produce fear conditioning [ 51 , 52 ]. Previous studies have shown that fear conditioning can be rapidly instilled in animals, even after a single conditioning trial, and is usually maintained for long periods [ 14 , 53 ]. This study observed that by increasing the number of CS-US pairings, the animals exhibited higher freezing responses, indicating a comparable level of learning during the training.…”