P2X7 receptors modulate acquisition of cue fear extinction and contextual background memory generalization in male mice.

The purinergic P2X7 receptors (P2X7R) are activated by adenosine triphosphate (ATP) in several brain regions, particularly those involved with emotional control and the regulation of fear-related memories. Here, we investigate the role of P2X7R in fear learning memory, specifically in the acquisition and consolidation phases of the cued fear conditioning paradigm. C57Bl/6 wildtype (WT) male mice that received a single i.

Fluoxetine and Ketamine Enhance Extinction Memory and Brain Plasticity by Triggering the p75 Neurotrophin Receptor Proteolytic Pathway.

Background: Diverse antidepressants were recently described to bind to TrkB (tyrosine kinase B) and drive a positive allosteric modulation of endogenous BDNF (brain-derived neurotrophic factor). Although neurotrophins such as BDNF can bind to p75NTR (p75 neurotrophin receptor), their precursors are the high-affinity p75NTR ligands. While part of an unrelated receptor family capable of inducing completely opposite physiological changes, TrkB and p75NTR feature a crosslike conformation dimer and carry a cholesterol-recognition amino acid consensus in the transmembrane domain.

Contextual fear expression engages a complex set of interactions between ventromedial prefrontal cortex cholinergic, glutamatergic, nitrergic and cannabinergic signaling.

Rats re-exposed to an environment previously associated with the onset of shocks evoke a set of conditioned defensive responses in preparation to an eventual flight or fight reaction. Ventromedial prefrontal cortex (vmPFC) is mutually important for controlling the behavioral/physiological consequences of stress exposure and the one's ability to satisfactorily undergo spatial navigation. While cholinergic, cannabinergic and glutamatergic/nitrergic neurotransmissions within the vmPFC are shown as important for modulating both behavioral and autonomic defensive responses, there is a gap on how these systems would interact to ultimately coordinate such conditioned reactions.

The times they are a-changin': a proposal on how brain flexibility goes beyond the obvious to include the concepts of "upward" and "downward" to neuroplasticity.

Since the brain was found to be somehow flexible, plastic, researchers worldwide have been trying to comprehend its fundamentals to better understand the brain itself, make predictions, disentangle the neurobiology of brain diseases, and finally propose up-to-date treatments. Neuroplasticity is simple as a concept, but extremely complex when it comes to its mechanisms. This review aims to bring to light an aspect about neuroplasticity that is often not given enough attention as it should, the fact that the brain's ability to change would include its ability to disconnect synapses.

The interaction between hippocampal cholinergic and nitrergic neurotransmission coordinates NMDA-dependent behavior and autonomic changes induced by contextual fear retrieval.

Rationale: Re-exposing an animal to an environment previously paired with an aversive stimulus evokes large alterations in behavioral and cardiovascular parameters. Dorsal hippocampus (dHC) receives important cholinergic inputs from the basal forebrain, and respective acetylcholine (ACh) levels are described to influence defensive behavior. Activation of muscarinic M1 and M3 receptors facilitates autonomic and behavioral responses along threats.

Dorsal hippocampal muscarinic cholinergic receptors orchestrate behavioral and autonomic changes induced by contextual fear retrieval.

Re-exposure of rats to a previously fear-conditioned environment arouses great alterations in behavioral and cardiovascular parameters. Pieces of works provide putative evidence for the contribution of the dorsal hippocampus (dHC) to contextual conditioning. dHC gathers massive cholinergic inputs from the basal forebrain, and dHC acetylcholine (ACh) is often described as triggering the retrieval of defensive behavior.

Fluoxetine acts concomitantly on dorsal and ventral hippocampus to Trk-dependently modulate the extinction of fear memory.

Background: Hippocampus can be divided along its longitudinal axis into dorsal and ventral parts, which play different roles in modulating the behavioral responses to stress. However, it is not clear whether the hippocampal subregions could also differently modulate the effect of antidepressant drugs. Since fluoxetine (FLX) effect on extinction of aversive memory is well known to depend on hippocampal BDNF levels, we hypothesized that the hippocampal subregions might play different roles in fluoxetine efficacy in decreasing fear response.