NMDA receptors (NMDARs) and AMPA receptors (AMPARs) in amygdala nuclei and the dorsal hippocampus (dHipp) are critical for fear conditioning. Enhancements in synaptic AMPAR expression in amygdala nuclei and the dHipp are critical for fear conditioning, with some studies observing changes in AMPAR expression across many neurons in these brain…

The medial temporal lobe (MTL), including the hippocampus (HC), perirhinal cortex (PRC), and parahippocampal cortex (PHC), is central to memory formation. Reward enhances memory through interplay between the HC and substantia nigra/ventral tegmental area (SNVTA). While the SNVTA also innervates the MTL cortex and amygdala (AMY), their role in…

Local protein synthesis at synapses can provide a rapid supply of proteins to support synaptic changes during consolidation of new memories, but its role in the maintenance or updating of established memories is unknown. Consolidation requires new protein synthesis in the period immediately following learning, whereas established memories are…

Episodic memories formed during infancy are rapidly forgotten, a phenomenon associated with infantile amnesia, the inability of adults to recall early-life memories. In both rats and mice, infantile memories, although not expressed, are actually stored long term in a latent form. These latent memories can be reinstated later in life by certain…

According to the active system consolidation theory, memory consolidation during sleep relies on the reactivation of newly encoded memory representations. This reactivation is orchestrated by the interplay of sleep slow oscillations, spindles, and theta, which are in turn modulated by certain neurotransmitters like GABA to enable long-lasting…

Research has shown that sleep is beneficial for the long-term retention of memories. According to theories of memory consolidation, memories are gradually reorganized, becoming supported by widespread, distributed cortical networks, particularly during postencoding periods of sleep. However, the effects of sleep on the organization of memories in…

The dopamine system has been implicated in decision-making particularly when associated with effortful behavior. We examined acute optogenetic stimulation of dopamine cells in the ventral tegmental area (VTA) as mice engaged in an effort-based decision-making task. Tyrosine hydroxylase-Cre mice were injected with Cre-dependent ChR2 or eYFP control…

Dysfunctions in memory recall lead to pathological fear; a hallmark of trauma-related disorders, like posttraumatic stress disorder (PTSD). Both, heightened recall of an association between a cue and trauma, as well as impoverished recall that a previously trauma-related cue is no longer a threat, result in a debilitating fear toward the cue.…

In an ever-changing environment, survival depends on learning which stimuli represent threat, and also on updating such associations when circumstances shift. It has been claimed that humans can acquire physiological responses to threat-associated stimuli even when they are unaware of them, but the role of awareness in updating threat…

The prefrontal cortex is larger than would be predicted by body size or visual cortex volume in great apes compared with monkeys. Because prefrontal cortex is critical for working memory, we hypothesized that recognition memory tests would engage working memory in orangutans more robustly than in rhesus monkeys. In contrast to working memory, the…

The ability to generate memories that persist throughout a lifetime (that is, memory persistence) emerges in early development across species. Although it has been shown that persistent fear memories emerge between late infancy and adolescence in mice, it is unclear exactly when this transition takes place, and whether two major fear conditioning…

Largely inspired from clinical concepts like brain reserve, cognitive reserve, and neural compensation, here we review data showing how neural circuits reorganize in presymptomatic and early symptomatic hAPP mice to maintain memory intact. By informing on molecular alterations and compensatory adaptations which take place in the brain before mice…

Individual differences in cognitive decline during normal aging and Alzheimer's disease (AD) are common, but the molecular mechanisms underlying these distinct outcomes are not fully understood. We utilized a combination of genetic, molecular, and behavioral data from a mouse population designed to model human variation in cognitive outcomes to…

A set of common-acting iron-responsive 5'untranslated region (5'UTR) motifs can fold into RNA stem loops that appear significant to the biology of cognitive declines of Parkinson's disease dementia (PDD), Lewy body dementia (LDD), and Alzheimer's disease (AD). Neurodegenerative diseases exhibit perturbations of iron homeostasis in defined brain…

Despite identical learning experiences, individuals differ in the memory formed of those experiences. Molecular mechanisms that control the neurophysiological bases of long-term memory formation might control how precisely the memory formed reflects the actually perceived experience. Memory formed with sensory specificity determines its utility…