Microbiota and social behavior alterations in a mouse model of down syndrome: Modulation by a synbiotic treatment.

Sex differences in the composition and functionality of gut microbiota are an emerging field of interest in neurodevelopmental disorders, as they may help in understanding the phenotypic disparities between males and females. This study aimed to characterize sex-related specific alterations in gut microbiota composition in a mouse model of Down syndrome (Ts65Dn mice, TS mice) through the sequencing of the PCR-amplified 16S ribosomal DNA fraction. Moreover, it intended to examine whether the modulation of gut microbiota by the administration of a synbiotic (SYN) treatment would be beneficial for the behavioral alterations observed in male and female TS mice.

Olfactory bulb astrocytes link social transmission of stress to cognitive adaptation in male mice.

Emotions and behavior can be affected by social chemosignals from conspecifics. For instance, olfactory signals from stressed individuals induce stress-like physiological and synaptic changes in naïve partners. Direct stress also alters cognition, but the impact of socially transmitted stress on memory processes is currently unknown.

Adolescent cannabinoid exposure rescues phencyclidine-induced social deficits through modulation of CA2 transmission.

Psychotic disorders entail intricate conditions marked by disruptions in cognition, perception, emotions, and social behavior. Notably, psychotic patients who use cannabis tend to show less severe deficits in social behaviors, such as the misinterpretation of social cues and the inability to interact with others. However, the biological underpinnings of this epidemiological interaction remain unclear.

Signaling-specific inhibition of the CB receptor for cannabis use disorder: phase 1 and phase 2a randomized trials.

Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB-SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ-tetrahydrocannabinol (THC) binding without modifying behavior per se.

Mitochondrial cannabinoid receptors gate corticosterone impact on novel object recognition.

Corticosteroid-mediated stress responses require the activation of complex brain circuits involving mitochondrial activity, but the underlying cellular and molecular mechanisms are scantly known. The endocannabinoid system is implicated in stress coping, and it can directly regulate brain mitochondrial functions via type 1 cannabinoid (CB) receptors associated with mitochondrial membranes (mtCB). In this study, we show that the impairing effect of corticosterone in the novel object recognition (NOR) task in mice requires mtCB receptors and the regulation of mitochondrial calcium levels in neurons.

Gene Expression Analysis of the Endocannabinoid System in Presymptomatic APP/PS1 Mice.

Alzheimer's disease (AD) is the most common type of dementia and neurodegeneration. The actual cause of AD progression is still unknown and no curative treatment is available. Recently, findings in human samples and animal models pointed to the endocannabinoid system (ECS) as a promising therapeutic approach against AD.

Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience.

There has been a renewed interest in the potential use of psychedelics for the treatment of psychiatric conditions. Nevertheless, little is known about the mechanism of action and molecular pathways influenced by ayahuasca use in humans. Therefore, for the first time, our study aims to investigate the human metabolomics signature after consumption of a psychedelic, ayahuasca, and its connection with both the psychedelic-induced subjective effects and the plasma concentrations of ayahuasca alkaloids.

Astroglial cannabinoid signaling and behavior.

In neuroscience, the explosion of innovative and advanced technical accomplishments is fundamental to understanding brain functioning. For example, the possibility to distinguish glial and neuronal activities at the synaptic level and/or the appearance of new genetic tools to specifically monitor and manipulate astroglial functions revealed that astrocytes are involved in several facets of behavioral control. In this sense, the discovery of functional presence of type-1 cannabinoid receptors in astrocytes has led to identify important behavioral responses mediated by this specific pool of cannabinoid receptors.

Special issue editorial: Cannabinoid signalling in the brain: New vistas.

The endocannabinoid system is widely expressed both in the brain and in the periphery. This system regulates a plethora of physiological functions and is composed of cannabinoid receptors, their endogenous ligands, and the enzymes involved in their metabolic processes. In the last few years, the development of new imaging and molecular tools has demonstrated that these receptors are distributed in many cell types (e.

Astroglial ER-mitochondria calcium transfer mediates endocannabinoid-dependent synaptic integration.

Intracellular calcium signaling underlies the astroglial control of synaptic transmission and plasticity. Mitochondria-endoplasmic reticulum contacts (MERCs) are key determinants of calcium dynamics, but their functional impact on astroglial regulation of brain information processing is unexplored. We found that the activation of astrocyte mitochondrial-associated type-1 cannabinoid (mtCB) receptors determines MERC-dependent intracellular calcium signaling and synaptic integration.

Neural Substrates of Incidental Associations and Mediated Learning: The Role of Cannabinoid Receptors.

The ability to form associations between different stimuli in the environment to guide adaptive behavior is a central element of learning processes, from perceptual learning in humans to Pavlovian conditioning in animals. Like so, classical conditioning paradigms that test direct associations between low salience sensory stimuli and high salience motivational reinforcers are extremely informative. However, a large part of everyday learning cannot be solely explained by direct conditioning mechanisms - this includes to a great extent associations between individual sensory stimuli, carrying low or null immediate motivational value.

Subcellular specificity of cannabinoid effects in striatonigral circuits.

Recent advances in neuroscience have positioned brain circuits as key units in controlling behavior, implying that their positive or negative modulation necessarily leads to specific behavioral outcomes. However, emerging evidence suggests that the activation or inhibition of specific brain circuits can actually produce multimodal behavioral outcomes. This study shows that activation of a receptor at different subcellular locations in the same neuronal circuit can determine distinct behaviors.

An Alternative Maze to Assess Novel Object Recognition in Mice.

The novel object recognition (NOR) task is a behavioral test commonly used to evaluate episodic-like declarative memory and it relies on the innate tendency of rodents to explore novelty. Here we present a maze used to evaluate NOR memory in mice that reduces the time of the assay while improving reliability of the measurements by increasing the exploratory behavior. This memory test, being performed in a two-arms maze, is suitable for several strains of mice (including inbreed and outbreed) and does not require extended training sessions allowing an accurate temporal assessment of memory formation.

A Novel Cortical Mechanism for Top-Down Control of Water Intake.

Water intake is crucial for maintaining body fluid homeostasis and animals' survival [1-4]. In the brain, complex processes trigger thirst and drinking behavior [1-5]. The anterior wall of the third ventricle formed by the subfornical organ (SFO), the median preoptic nucleus, and the organum vasculosum of the lamina terminalis (OVLT) constitute the primary structures sensing thirst signals and modulating water intake [6-10].

Protein Kinase C-Gamma Knockout Mice Show Impaired Hippocampal Short-Term Memory While Preserved Long-Term Memory.

The brain encodes, stores, and retrieves relevant information in the form of memories that are classified as short-term (STM) and long-term memories (LTM) depending on the interval between acquisition and retrieval. It is classically accepted that STM undergo a consolidation process to form LTM, but the molecular determinants involved are not well understood. Among the molecular components relevant for memory formation, we focused our attention on the protein kinase C (PKC) family of enzymes since they control key aspects of the synaptic plasticity and memory.

Specific Hippocampal Interneurons Shape Consolidation of Recognition Memory.

A complex array of inhibitory interneurons tightly controls hippocampal activity, but how such diversity specifically affects memory processes is not well understood. We find that a small subclass of type 1 cannabinoid receptor (CBR)-expressing hippocampal interneurons determines episodic-like memory consolidation by linking dopamine D receptor (DR) signaling to GABAergic transmission. Mice lacking CBRs in D-positive cells (D-CB-KO) display impairment in long-term, but not short-term, novel object recognition memory (NOR).

Sex-dependent pharmacological profiles of the synthetic cannabinoid MMB-Fubinaca.

Synthetic cannabinoids have emerged as novel psychoactive substances with damaging consequences for public health. They exhibit high affinity at the cannabinoid type-1 (CB ) receptor and produce similar and often more potent effects as other CB receptor agonists. However, we are still far from a complete pharmacological understanding of these compounds.

Glucose metabolism links astroglial mitochondria to cannabinoid effects.

Astrocytes take up glucose from the bloodstream to provide energy to the brain, thereby allowing neuronal activity and behavioural responses. By contrast, astrocytes are under neuronal control through specific neurotransmitter receptors. However, whether the activation of astroglial receptors can directly regulate cellular glucose metabolism to eventually modulate behavioural responses is unclear.

CB1 Receptors in the Anterior Piriform Cortex Control Odor Preference Memory.

The retrieval of odor-related memories shapes animal behavior. The anterior piriform cortex (aPC) is the largest part of the olfactory cortex, and it plays important roles in olfactory processing and memory. However, it is still unclear whether specific cellular mechanisms in the aPC control olfactory memory, depending on the appetitive or aversive nature of the stimuli involved.

The motivation for exercise over palatable food is dictated by cannabinoid type-1 receptors.

The lack of intrinsic motivation to engage in, and adhere to, physical exercise has major health consequences. However, the neurobiological bases of exercise motivation are still unknown. This study aimed at examining whether the endocannabinoid system (ECS) is involved in this process.