The expression of contextual fear conditioning involves the dorsal hippocampus TRPV1 receptor interacting with the NMDA/NO/cGMP signalling pathway.

Background And Purpose: The dorsal hippocampus (dHIP) is pivotal for learning, memory, and defensive responses. Transient receptor potential vanilloid type 1 (TRPV1) receptors in the dHIP modulate contextual fear conditioning by triggering a cascade involving glutamate release, nitric oxide (NO) formation and cyclic guanosine monophosphate (cGMP) production. The present study investigated the involvement of dHIP TRPV1 receptors and their interaction with the glutamate/NO/cGMP signalling pathway in modulating the expression of contextual fear conditioning (CFC).

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.

The influence of paraventricular nucleus of the hypothalamus soluble guanylate cyclase on autonomic and neuroendocrine responses to acute restraint stress in rats.

The paraventricular nucleus of the hypothalamus (PVN) regulates physiological and behavioural responses evoked by stressful stimuli, but the local neurochemical and signalling mechanisms involved are not completely understood. The soluble guanylate cyclase (sGC) within the PVN is implicated in autonomic and cardiovascular control in rodents under resting conditions. However, the involvement of PVN sGC-mediated signalling in stress responses is unknown.

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.

Neuroprotective Profile of Triazole Grandisin Analogue against Amyloid-Beta Oligomer-Induced Cognitive Impairment.

Alzheimer's disease (AD) is a neurodegenerative disorder caused by accumulation of amyloid-β oligomers (AβO) in the brain, neuroinflammation, oxidative stress, and cognitive decline. Grandisin, a tetrahydrofuran neolignan, exhibits relevant anti-inflammatory and antioxidant properties. Interestingly, grandisin-based compounds were shown to prevent AβO-induced neuronal death in vitro.

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.

Bed nucleus of the stria terminalis CB1 receptors and the FAAH enzyme modulate anxiety behavior depending on previous stress exposure.

The endocannabinoid (eCB) anandamide (AEA) is synthesized on-demand in the post-synaptic terminal and can act on presynaptic cannabinoid type 1 (CB1) receptors, decreasing the release of neurotransmitters, including glutamate. AEA action is ended through enzymatic hydrolysis via FAAH (fatty acid amid hydrolase) in the post-synaptic neuron. eCB system molecules are widely expressed in brain areas involved in the modulation of fear and anxiety responses, including the Bed Nucleus of the Stria Terminalis (BNST), which is involved in the integration of autonomic, neuroendocrine, and behavioral regulation.

The medial prefrontal cortex and the cardiac baroreflex activity: physiological and pathological implications.

The cardiac baroreflex is an autonomic neural mechanism involved in the modulation of the cardiovascular system. It influences the heart rate and peripheral vascular resistance to preserve arterial blood pressure within a narrow variation range. This mechanism is mainly controlled by medullary nuclei located in the brain stem.

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.

Distinct sex-dependent behavioral responses induced by two positive allosteric modulators of alpha 5 subunit-containing GABA receptors.

Dysregulation of GABAergic neurotransmission has long been implicated in several psychiatric disorders, including schizophrenia, depression, and anxiety disorders. Alpha 5 subunit-containing GABA receptors (α5-GABAR), which are expressed mainly by pyramidal neurons in the hippocampus, have been proposed as a potential target to treat these psychiatric disorders. Here, we evaluated the effects produced by GL-II-73 and SH-053-2'F-R-CH3 (1, 5, and 10 mg/kg), two positive allosteric modulators of α5-GABAR in behavioral tests sensitive to drugs with anxiolytic, antidepressant, and antipsychotic properties in male and female C57BL/6 mice.

Ventromedial prefrontal cortex CRF1 receptors modulate the tachycardic activity of baroreflex.

Ventral medial prefrontal cortex (vMPFC) glutamatergic neurotransmission has a facilitatory role on cardiac baroreflex activity which is mediated by NMDA receptors activation. Corticotrophin releasing factor receptors type1 and 2 (CRF1 and CRF2), present in the vMPFC, are colocalized in neurons containing glutamate vesicles, suggesting that such receptors may be involved in glutamate release in this cortical area. Therefore, our hypothesis is that the CRF1 and CRF2 receptors can modulate the baroreflex bradycardic and tachycardic responses.

κ-Opioid receptors in the medial amygdaloid nucleus modulate autonomic and neuroendocrine responses to acute stress.

The medial amygdaloid nucleus (MeA) is a key neural structure in triggering physiologic and behavioral control during aversive situations. However, MeA role during stress exposure has not yet been fully elucidated. Thus, in the present study, we investigated the involvement of the MeA opioid neurotransmission in the modulation of autonomic, neuroendocrine and behavioral responses evoked by acute restraint stress (RS).

Bed nucleus of the stria terminalis modulates baroreflex cardiac activity: an interaction between alpha-1 receptors and NMDA/nitric oxide pathway.

The bed nucleus of the stria terminalis (BNST) is a forebrain structure, involved in the modulation of neuroendocrine, cardiovascular and autonomic responses. One of the responses is baroreflex activity, which consists in a neural mechanism responsible for keeping the blood pressure within a narrow range of variation. It has been reported that blockade of BNST α-adrenoceptors increased the bradycardic component of baroreflex.

Nitric oxide in the insular cortex modulates baroreflex responses in a cGMP-independent pathway.

Insular cortex is a brain structure involved in the modulation of autonomic activity and cardiovascular function. The nitric oxide/cyclic guanosine-3',5'-monophosphate pathway is a prominent signaling mechanism in the central nervous system, controlling behavioral and physiological responses. Nevertheless, despite evidence regarding the presence of nitric oxide-synthesizing neurons in the insular cortex, its role in the control of autonomic and cardiovascular function has never been reported.

Dorsal hippocampus cholinergic and nitrergic neurotransmission modulates the cardiac baroreflex function in rats.

Hippocampus is a limbic structure involved in the baroreflex and chemoreflex control that receives extensive cholinergic input from basal forebrain. Hippocampal muscarinic receptors activation by acetylcholine might evoke nitric oxide synthesis, which is an important neuromodulator of cardiovascular responses. Thus, we hypothesize that cholinergic and nitrergic neurotransmission within the DH modulates the baroreflex and chemoreflex function.

Effect of chronic stress on cardiovascular and ventilatory responses activated by both chemoreflex and baroreflex in rats.

Chronic stress results in physiological and somatic changes. It has been recognized as a risk factor for several types of cardiovascular dysfunction and changes in autonomic mechanisms, such as baroreflex and chemoreflex activity. However, the effects of different types of chronic stress on these mechanisms are still poorly understood.

Nitrergic neurotransmission in the paraventricular nucleus of the hypothalamus modulates autonomic, neuroendocrine and behavioral responses to acute restraint stress in rats.

We investigated the involvement of nitrergic neurotransmission within the paraventricular nucleus of the hypothalamus (PVN) in modulation of local neuronal activation, autonomic and neuroendocrine responses and behavioral consequences of acute restraint stress in rats. Bilateral microinjections of the selective neuronal nitric oxide (NO) synthase (nNOS) inhibitor N-Propyl-L-arginine (NPLA) or the NO scavenger carboxy-PTIO into the PVN reduced arterial pressure and heart rate increases, as well as the fall in cutaneous tail temperature induced by restraint stress. PVN injection of either NPLA or carboxy-PTIO also inhibited restraint-induced increases in anxiety-related behaviors in the elevated plus-maze 24 h later.

Fear extinction disruption in a developmental rodent model of schizophrenia correlates with an impairment in basolateral amygdala-medial prefrontal cortex plasticity.

Schizophrenia patients typically exhibit prominent negative symptoms associated with deficits in extinction recall and decreased ventromedial prefrontal cortex activity (vmPFC, analogous to medial PFC infralimbic segment in rodents). mPFC activity modulates the activity of basolateral amygdala (BLA) and this connectivity is related to extinction. mPFC and BLA activity has been shown to be altered in the methylazoxymethanol acetate (MAM) developmental disruption model of schizophrenia.

Medial prefrontal cortex TRPV1 and CB1 receptors modulate cardiac baroreflex activity by regulating the NMDA receptor/nitric oxide pathway.

The ventral medial prefrontal cortex (vMPFC) facilitates the cardiac baroreflex response through N-methyl-D-aspartate (NMDA) receptor activation and nitric oxide (NO) formation by neuronal NO synthase (nNOS) and soluble guanylate cyclase (sGC) triggering. Glutamatergic transmission is modulated by the cannabinoid receptor type 1 (CB) and transient receptor potential vanilloid type 1 (TRPV) receptors, which may inhibit or stimulate glutamate release in the brain, respectively. Interestingly, vMPFC CB receptors decrease cardiac baroreflex responses, while TRPV channels facilitate them.

Neuroreflex control of cardiovascular function is impaired after acute poisoning with chlorpyrifos, an organophosphorus insecticide: Possible short and long term clinical implications.

Although it is well-established that severe poisoning by organophosphorus (OP) compounds strongly affects the cardiorespiratory system, the effects of sub-lethal exposure to these compounds on the neural control of cardiovascular function are poorly explored. The aim of this study was to evaluate the effects of acute sub-lethal exposure to chlorpyrifos (CPF), a commonly used OP insecticide, on three basic reflex mechanisms involved in blood pressure regulation, the peripheral chemoreflex, the baroreflex and the Bezold-Jarisch reflex. Adult male Wistar rats were injected intraperitoneally with a single dose of CPF (30 mg/kg) or saline (0.

Treatment with escitalopram modulates cardiovascular function in rats.

Considering depression is three times more common in cardiac patients compared to the normal population and selective serotonin reuptake inhibitors (SSRI) as drug of choice for treating patients with cardiovascular disease and depression, our work aims to evaluate the cardiovascular effects of treatment for 21 days with escitalopram (5 mg/kg/day, ip) in rats. The treatment caused an increase in mean arterial pressure concomitant with a decrease in heart rate. Concerning heart rate variability, there was a significant reduction in the sympathetic component and an elevation of the parasympathetic component, indicating that escitalopram caused an autonomic imbalance with parasympathetic predominance.

Glutamatergic, GABAergic, and endocannabinoid neurotransmissions within the dorsal hippocampus modulate the cardiac baroreflex function in rats.

The dorsal hippocampus (DH) is involved in the modulation of the cardiac baroreflex function. There is a wide expression of the NMDA and AMPA/Kainate receptors within the DH. Glutamate administration into the DH triggers both tachycardia and pressor responses.