A single brief stressful event time-dependently affects object recognition memory and promotes familiarity preference in marmoset monkeys.

A stressful experience can enhance information storage and impair memory retrieval in the rodent novel object recognition (NOR) task. However, recent conflicting results underscore the need for further investigation. Nonhuman primates may provide a unique, underexplored and more translational means to investigate stress-mediated changes in memory. Therefore, we assessed whether a single brief extrinsic stress event affects information encoding, storage and/or retrieval in adult marmoset monkeys submitted to the NOR task. This consisted of an initial 10 min familiarization period with two identical neutral objects. After a 6 h delay, a 10 min test trial was held where a new and familiar object could be explored. Stress was induced by a 15 min restraint event held before or after the encoding phase, or prior to retrieval. Pre-encoding stress had no effect on task performance, as this group displayed above-chance novelty preference similar to non-stressed controls. Post-encoding stress induced memory deficits, with both objects being explored equally. Interestingly, pre-retrieval stress induced an above-chance familiarity preference. A single brief stressful event thus affects recognition memory in a time-dependent manner. Also, negative discrimination ratios can be used as a measure of memory in the NOR task and a change in strategy may not mean memory failure in spontaneous learning paradigms.

Scopolamine and MK-801 impair recognition memory in a new spontaneous object exploration task in monkeys.

The spontaneous object recognition (SOR) task is one of the most widely used behavioral protocols to assess visual memory in animals. However, only recently was it shown that nonhuman primates also perform well on this task. Here we further characterized this new monkey recognition memory test by assessing the performance of adult marmosets after an acute systemic administration of two putative amnesic agents: the competitive muscarinic acetylcholine receptor antagonist scopolamine (SCP; 0.05 mg/kg) and the noncompetitive N-methyl-d-aspartate glutamate receptor antagonist MK-801 (0.015 mg/kg). We also determined whether the acetylcholinesterase inhibitor donepezil (DNP; 0.50 mg/kg), a clinically-used cognitive enhancer, reverses memory deficits caused by either drug. The subjects had an initial 10 min sample trial where two identical neutral objects could be explored. After a 6 h retention interval, recognition was based on an exploratory preference for a new rather than familiar object during a 10 min test trial. Both SCP and MK-801 impaired the marmosets' performance on the SOR task, as both objects were explored equivalently. Co-administration of 0.50 mg/kg of DNP reversed the SCP- but not the MK-801-induced memory deficit. These results indicate that cholinergic and glutamatergic pathways mediate object recognition memory in the monkey SOR task.

Neutral Sphingomyelinase is an Affective Valence-Dependent Regulator of Learning and Memory.

Sphingolipids and enzymes of the sphingolipid rheostat determine synaptic appearance and signaling in the brain, but sphingolipid contribution to normal behavioral plasticity is little understood. Here we asked how the sphingolipid rheostat contributes to learning and memory of various dimensions. We investigated the role of these lipids in the mechanisms of two different types of memory, such as appetitively and aversively motivated memory, which are considered to be mediated by different neural mechanisms. We found an association between superior performance in short- and long-term appetitively motivated learning and regionally enhanced neutral sphingomyelinase (NSM) activity. An opposite interaction was observed in an aversively motivated task. A valence-dissociating role of NSM in learning was confirmed in mice with genetically reduced NSM activity. This role may be mediated by the NSM control of N-methyl-d-aspartate receptor subunit expression. In a translational approach, we confirmed a positive association of serum NSM activity with long-term appetitively motivated memory in nonhuman primates and in healthy humans. Altogether, these data suggest a new sphingolipid mechanism of de-novo learning and memory, which is based on NSM activity.

Neutral ceramidase is a marker for cognitive performance in rats and monkeys.

BACKGROUND: Ceramides are lipid molecules determining cell integrity and intercellular signaling, and thus, involved in the pathogenesis of several psychiatric and neurodegenerative disorders. However, little is known about the role of particular enzymes of the ceramide metabolism in the mechanisms of normal behavioral plasticity. Here, we studied the contribution of neutral ceramidase (NC), one of the main enzymes mediating ceramide degradation, in the mechanisms of learning and memory in rats and non-human primates. METHODS: Naïve Wistar rats and black tufted-ear marmosets (Callithrix penicillata) were tested in several tests for short- and long-term memory and then divided into groups with various memory performance. The activities of NC and acid ceramidase (AC) were measured in these animals. Additionally, anxiety and depression-like behavior and brain levels of monoamines were assessed in the rats. RESULTS: We observed a predictive role of NC activity in the blood serum for superior performance of long-term object memory tasks in both species. A brain area analysis suggested that high NC activity in the ventral mesencephalon (VM) predicts better short-term memory performance in rats. High NC activity in the VM was also associated with worse long-term object memory, which might be mediated by an enhanced depression-like state and a monoaminergic imbalance. CONCLUSIONS: Altogether, these data suggest a role for NC in short- and long-term memory of various mammalian species. Serum activity of NC may possess a predictive role in the assessing the performance of certain types of memory.