Bernard Hars

Contextual cues and memory retrieval in rats: Alleviation of forgetting by a pretest exposure to background stimuli

With a relatively complex maze, reliable forgetting is clearly seen when the training-test interval is 25 days. This forgetting is evidenced by the longer time taken to run the maze and in an increase in the number of errors from the last training trial to the first test trial. In this case, forgetting is a lapse, not a loss, since performance attains the last training trial level at a subsequent test. Furthermore, a reminder which does not in itself contain sufficient information to facilitate performance of a naive animal, significantly improves maze performance of animals which have “forgotten,” even on the first retention test. With the use of additional control groups, it is shown that there must be a memory lapse before contextual cues can be demonstrated to be effective in facilitating memory retrieval.

Improvement of learning by cueing during postlearning paradoxical sleep.

Rats were submitted to an active avoidance conditioning in a shuttle box with slight ear shocks used as conditioned stimulus (CS) preceding a foot shock. Three conditioning sessions were performed with a 24 h intersession interval. Animals were divided into 3 groups. After each session, the first group received the CS as cue during the first 6 phases of paradoxical sleep (PS) following learning. The second group received the CS as cue during 6 periods of wakefulness. The third group received no cue. Animals cued during PS showed a significant improvement in performances. The effect of cueing during the awake state appeared to be marginal compared to the clear-cut effects when the cue was presented during PS. A control experiment showed that the same ear shocks presented during PS were ineffective when they were not associated with the learning task (in this experiment a tone was used as CS during conditioning). These results are discussed in terms of memory reactivation during postlearning paradoxical sleep.

Memory Consolidation and Reconsolidation in the Rat Pup Require Protein Synthesis

Little is known about the ontogenesis of memory, whether it appears with its full characteristics or whether they emerge progressively with development. In the adult, basic characteristics of memory processing are consolidation of memory after acquisition and reconsolidation after retrieval. Here, using a conditioned aversion paradigm and postlearning or postreactivation injection of a protein synthesis inhibitor, we show that memory acquired by rat pups as early as postnatal day 3 requires time-dependent protein synthesis after both learning and reactivation. These results present the first evidence suggesting that consolidation and reconsolidation are original properties of memory function.

Reticular stimulation facilitates retrieval of a ‘forgotten’ maze habit

Rats tested 25 days after training in a complex maze showed significant forgetting. Stimulation of the mesencephalic reticular formation immediately prior to retention testing facilitated performance in that stimulated rats made fewer errors (but did not run faster) than non-stimulated controls. Rats exposed to a contextual cue as a reminder before testing ran faster and made fewer errors than controls. Results are discussed in terms of forgetting being due to retrieval failure, and the reticular stimulation facilitating retrieval of information concerning the spatial configuration of the maze.

Extracellular signal‐regulated kinase activation is required for consolidation and reconsolidation of memory at an early stage of ontogenesis

The ability to form long‐term memories exists very early during ontogeny; however, the properties of early memory processes, brain structures involved and underlying cellular mechanisms are poorly defined. Here, we examine the role of extracellular signal‐regulated kinase (ERK), a member of the mitogen‐activated protein kinase/ERK signaling cascade, which is crucial for adult memory, in the consolidation and reconsolidation of an early memory using a conditioned taste aversion paradigm in 3‐day‐old rat pups. We show that intraperitoneal injection of SL327, the upstream mitogen‐activated protein kinase kinase inhibitor, impairs both consolidation and reconsolidation of early memory, leaving short‐term memory after acquisition and after reactivation intact. The amnesic effect of SL327 diminishes with increasing delays after acquisition and reactivation. Biochemical analyses revealed ERK hyperphosphorylation in the amygdala but not the hippocampus following acquisition, suggesting functional activation of the amygdala as early as post‐natal day 3, although there was no clear evidence for amygdalar ERK activation after reactivation. These results indicate that, despite an immature brain, the basic properties of memory and at least some of the molecular mechanisms and brain structures implicated in aversion memory share a number of similarities with the adult and emerge very early during ontogeny.

Is increase in post-learning paradoxical sleep modified by cueing?

Rats were submitted to three sessions of an active avoidance conditioning. The conditioned stimulus (CS) was either an ear shock or a tone. Sleep was measured after each session. Experimental animals received non-awakening ear shocks during post-learning paradoxical sleep (PS). When ear shocks were the CS and were subsequently used as cues during PS, PS increases were observed, but they displayed 2 unusual characteristics: they were due to longer average size of PS phases rather than to higher number of phases as usually; PS did not return to baseline level even when learning seemed to be achieved. By contrast, when ear shocks were not associated with conditioning, animals shocked during PS exhibited the usual PS increases.

Reminder abolishes impairment of learning induced by paradoxical sleep retardation

Rats were submitted to one daily trial in a relatively complex maze. When sleep was delayed (by the water tank technique) for 180 min after each trial, learning was impaired. A reminder treatment (90 sec exposure to contextual cues) immediately before each trial, counteracted the effects of sleep deprivation. The reminder did not in itself contain sufficient information to facilitate performance of non sleep delayed animals. These results suggest that a retrieval failure is involved in memory impairment caused by post-learning paradoxical sleep deprivation.

Pheromone-induced olfactory memory in newborn rabbits: Involvement of consolidation and reconsolidation processes.

Mammary pheromone (MP)-induced odor memory is a new model of appetitive memory functioning early in a mammal, the newborn rabbit. Some properties of this associative memory are analyzed by the use of anisomycin as an amnesic agent. Long-term memory (LTM) was impaired by anisomycin delivered immediately, but not 4 h after either acquisition or reactivation. Thus, the results suggest that this form of neonatal memory requires both consolidation and reconsolidation. By extending these notions to appetitive memory, the results reveal that consolidation and reconsolidation processes are characteristics of associative memories of positive events not only in the adult, but also in the newborn.

The temporal dynamics of consolidation and reconsolidation decrease during postnatal development.

The temporal dynamics of consolidation and reconsolidation of taste/odor aversion memory are evaluated during rat pup growth at postnatal days 3, 10, and 18. This is assessed through the temporal gradients of efficacy of a protein synthesis inhibitor (anisomycin) in inducing amnesia after either acquisition (consolidation) or reactivation (reconsolidation). The results show a progressive reduction with age of the delay during which the inhibitor is able to induce amnesia. Control experiments rule out a reduction of anisomycin efficacy due to blood brain barrier growth or decrease in protein synthesis inhibition. Thus, these results present the first evidence that the protein synthesis-dependent phase of memory stabilization requires less time with age. This decrease occurs in parallel for consolidation and reconsolidation. Such changes in the dynamics of memory processing could contribute to the cognitive improvement associated with development.

Independence of first- and second-order memories in newborn rabbits.

The mammary pheromone promotes the acquisition of novel odorants (CS1) in newborn rabbits. Here, experiments pinpoint that CS1 becomes able to support neonatal learning of other odorants (CS2). We therefore evaluated whether these first- and second-order memories remained dependent after reactivation. Amnesia induced after CS2 recall selectively blocked this memory, when recall and amnesia of CS1 left the souvenir of CS2 safe; this finding partially differed from results obtained in adult mammals. Thus, in this model of neonatal appetitive odor learning, second-order memory seems to depend on first-order memory for its formation but not for its maintenance.