Neuroscience
-
In this review we explore the role of the perirhinal cortex (Prh) in memory, focusing on the cellular and molecular mechanisms that have been described to happen in this structure. The Prh is part of the medial temporal lobe, but the evidences show that it has a different function than that of the hippocampus. ⋯ We discuss a series of studies of memory and plasticity in this region and how they might relate. In addition, we propose that Prh could play a role as a "pattern separator" for object memories, similar to the function of the dentate gyrus of the hippocampus in the spatial domain.
-
Posttraumatic stress and drug use disorders may stem from aberrant memory formation. As the endocannabinoid (eCB) system has a pivotal role in emotional memory processing and related synaptic plasticity, here we seek to review and discuss accumulating evidence on how and where in the brain interventions targeting the eCB system would attenuate outcomes associated with traumatic events and/or drug addiction through memory extinction facilitation or reconsolidation disruption. Currently available data from mouse, rat, monkey and healthy human studies investigating the effects of cannabinoid drugs on extinction and reconsolidation of aversive memories are more consistent than those related to rewarding drug-associated memories. ⋯ Brain areas in which cannabinoid drugs induce these effects include the prefrontal cortex, amygdala, hippocampus, and/or nucleus accumbens. The potential role of 2-arachidonoylglycerol (2-AG) and cannabinoid type-2 (CB2) receptors in emotional memory extinction and reconsolidation is currently under investigation. Overall, preclinical data support a closer look into certain cannabinoid drugs owing to their safety and potential therapeutic value against stress-related and drug use disorders.
-
At the neuronal cell level, long-term memory formation emerges from interactions between initial activity-dependent molecular changes at the synapse and subsequent regulation of gene transcription in the nucleus. This in turn leads to strengthening of the connections back at the synapse that received the initial signal. However, the mechanisms through which this synapse-to-nucleus molecular exchange occurs remain poorly understood. Here we discuss recent studies that delineate nucleocytoplasmic transport of a special class of synaptically localized transcriptional regulators that upon receiving initial external signal by the synapse move to the nucleus to modulate gene transcription.
-
The hippocampus enables a range of behaviors through its intrinsic circuits and concerted actions with other brain regions. One such important function is the retrieval of episodic memories. How hippocampal cells support retrieval of contextual fear memory remains largely unclear. ⋯ Moreover, retrieval preferentially re-activated Erk1/2 in the same set of CA1 neurons previously activated during conditioning in a context-specific manner. By confining drug inhibition within dorsal CA1, we established the crucial role for Erk1/2 activity in retrieval of long-term memory, as well as in amygdala activation associated with fear expression. These data provide functional evidence that Erk1/2 signaling in CA1 encodes a specific neural representation of contextual memory with emotional value.
-
Potocki-Shaffer Syndrome is a rare neurodevelopmental syndrome associated with microdeletion of a region of Chromosome 11p11.2. Genetic evidence has implicated haploinsufficiency of PHF21A, a gene that encodes a histone-binding protein, as the likely cause of intellectual disability and craniofacial abnormalities in Potocki-Shaffer Syndrome. However, the molecular consequences of reduced PHF21A expression remain elusive. ⋯ Finally, PHF21A-deficient patient-derived cells exhibited a delayed induction of immediate early genes following forskolin stimulation. These results suggest that an impaired response to cAMP signaling might be involved in the pathology of PHF21A deficiency. This article is part of a Special Issue entitled: [SI: Molecules & Cognition].