Cerebellar ataxias represent a spectrum of disorders which are, however, linked by common symptoms of motor incoordination and typically associated with deficiency in Purkinje cell firing activity and, often, degeneration. Cerebellar ataxias currently lack a curative agent. The endocannabinoid (eCB) system includes eCB compounds and their associated metabolic enzymes, together with cannabinoid ...

Experience-driven plasticity of glutamatergic synapses on striatal spiny projection neurons (SPNs) is thought to be essential to goal-directed behavior and habit formation. One major form of striatal plasticity, long-term depression (LTD), has long appeared to be expressed only pre-synaptically. Contrary to this view, nitric oxide (NO) generated by striatal interneurons was found to induce a po...

Understanding how striatal neurons integrate glutamatergic and GABAergic inputs is essential for understanding the control of movement and the formation of striatal-based memories. Here we show that GABAergic synapses on striatal medium spiny neurons (MSNs) are more sensitive than glutamatergic synapses on the same cells to endocannabinoid (eCB) signaling, and that protocols that induce short-l...

The basal ganglia play a critical role in shaping motor behavior. For this function, the activity of medium spiny neurons (MSNs) of the striatonigral and striatopallidal pathways must be integrated. It remains unclear whether the activity of the two pathways is primarily coordinated by synaptic plasticity mechanisms. Using a model of Parkinson's disease, we determined the circuit and behavioral...

During brain development, neurogenesis is precisely regulated by the concerted action of intrinsic factors and extracellular signalling systems that provide the necessary niche information to proliferating and differentiating cells. A number of recent studies have revealed a previously unknown role for the endocannabinoid (ECB) system in the control of embryonic neuronal development and maturat...

Abstract Biological mechanisms associated with response to trauma may impact risk for depression. One such mechanism is endocannabinoid signaling (eCB), a neuromodulatory system comprised of the CB1 subtype cannabinoid receptors (CB1R), encoded by CNR1 gene, and two primary endogenous ligands: 2-arachidonoylglycerol (2-AG) N-arachidonylethanolamine (AEA), hydrolyzed monoacylglycerol lipase (gen...

BACKGROUND Fatty acid amide hydrolase (FAAH) is a key enzyme in regulating endocannabinoid (eCB) signaling. A common single nucleotide polymorphism (C385A) in the human FAAH gene has been associated with increased risk for addiction and obesity. METHODS Using imaging genetics in 82 healthy adult volunteers, we examined the effects of FAAH C385A on threat- and reward-related human brain functi...

Purpose To investigate whether the subcellular distribution of endocannabinoid (eCB) system (ECS) components in growing RGC axons is consistent with the formation of eCB-enriched "hotspots" and the role of the ECS in RGC axonal growth. Methods We used immunocytochemistry and image analysis to quantify axonal expression of the ECS components diacylglycerol lipase alpha (DGLα), monoacylglycerol...

The serine hydrolase α/β-hydrolase domain 6 (ABHD6) hydrolyzes the most abundant endocannabinoid (eCB) in the brain, 2-arachidonoylglycerol (2-AG), and controls its availability at cannabinoid receptors. We show that ABHD6 inhibition decreases pentylenetetrazole (PTZ)-induced generalized tonic-clonic and myoclonic seizure incidence and severity. This effect is retained in Cnr1(-/-) or Cnr2(-/-)...

Upon the identification of anandamide (AEA) in the porcine brain, numerous studies contributed to the current state of knowledge regarding all elements that form the "endocannabinoid system (ECS)."How this complex system of receptors, ligands, and enzymes is integrated in helping to regulate fundamental processes at level of central nervous and peripheral systems and how its regulation and dysr...