Topic: endocannabinoids

Stroke is a leading cause of long-term disability worldwide with substantial economic costs. Hence, there is an urge for finding novel therapies to treat disability associated to stroke. This is the main reason research has focused on the discovery of key molecules involved in the functional prognosis of patients after stroke. Adenosine A2A and CB2 are receptors that have proven to be a new therapeutic target to consider in treatment of stroke. A common feature of these receptors in neurons is that their expression is upregulated in neuroinflammation process. On the one hand CB2R show a neurop

Stress induces aversive memory overgeneralization, a hallmark of many psychiatric disorders. Memories for events are encoded by a sparse ensemble of principal neurons active during an event, termed an engram ensemble. Using engram labeling tools, molecular sensors, optogenetics and CRISPR-Cas9 gene editing in specific neuronal populations we examined the molecular and circuit processes mediating stress-induced threat memory overgeneralization in mice. We found that stress, acting via corticosterone, increases the density of engram ensembles supporting a threat memory and this less sparse engra

Theta oscillations (4-12 Hz) in the hippocampus are caused by the synchronous bursting activity of neuronal populations. They are critical for grouping and selecting neuronal ensembles in the context of spatial navigation, memory, and learning, but the reason why this frequency band is particularly effective for adjusting neuronal ensembles remains speculative. Here we show that burst activity at the CA3-CA1 synapse of the mouse hippocampus leads to a rapid activation of astrocytic leaflets possibly via the retrograde release of endocannabinoids that activate transient receptor potential chann

A cognitive model of stress posits that psycho-affective disorders can arise from a perceived lack of stress control. Uncontrollability is linked to perturbed prefrontocortical (PFC)-limbic signalling of endocannabinoids (anandamide) and altered hormonal activity (prolactin and glucocorticoids). Behavioural therapies such as cognitive-behavioural/remediation therapies ameliorate symptoms by enhancing perceived controllability. There is also evidence that augmenting endocannabinoid and hormonal levels results in antidepressant/anti-stress action. Based on a modified version of the rodent Morris

Oligodendrocytes produce central nervous system myelin and provide metabolic support to axons. Myelin formation and repair are energetically expensive and oligodendrocyte metabolic defects have been postulated as a cause of neurodegeneration. Endocannabinoids modulate neuronal and astroglial metabolism and attenuate inflammatory demyelination in multiple sclerosis (MS) through the activation of CB1 receptors (CB1Rs). Myelinating oligodendrocytes and precursor cells (OPCs) express CB1Rs that mediate protection from excitotoxicity and promote lineage progression but the metabolic implications of

Astrocytes play a key role in the regulation of synaptic strength and are thought to orchestrate synaptic plasticity and memory. Yet, how specifically astrocytes and their neuroactive transmitters control learning and memory is currently an open question. Recent experiments have uncovered an astrocyte-mediated feedback loop in CA1 pyramidal neurons which is started by the release of endocannabinoids by active neurons and closed by astrocytic regulation of the D-serine levels at the dendrites.D-serine is a co-agonist for the NMDA receptor regulating the strength and direction of synaptic plasti

The entorhinal cortex (EC) connects to the hippocampus sending different information from cortical areas that is first processed at the dentate gyrus (DG) including spatial, limbic, and sensory and information. Excitatory afferents from lateral (LPP) and medial (MPP) perforant pathways of the EC connecting to granule cells (GC) of the DG play a role in memory encoding and information processing. LPP- and MPP-GC synapses have distinct electrophysiological properties, and these differences potentially affecting the functional processing of information. However, the plasticity of these synapses i

The formation of new inhibitory synapses is essential to counterbalance a strong excitatory activity and maintain dendritic coordination between excitation and inhibition. We recently demonstrated that the activation of excitatory spines is followed by the production of endocannabinoids in dendrites, which mediates the formation of new inhibitory boutons via axonal CB1 receptors. Bouton formation was found to depend on an increase of the second messenger cyclic adenosine monophosphate (cAMP) and the activation of the downstream protein kinase A (PKA). We ask whether other neuromodulators are a

GABAergic neurotransmission generates two types of inhibitions: the transient activation of synaptic GABA receptors, or phasic inhibition, which elicits inhibitory postsynaptic currents, and the activation of extrasynaptic GABA receptors by “ambient” GABA which causes a persistent, “tonic”, inhibition that finely tunes cellular excitability of target neurons. Change in GABA synaptic efficacy is a crucial mechanism that underlies experience-dependent modifications of brain function. Several forms of GABA synaptic plasticity require retrograde signaling by endocannabinoids (eCB) through the acti