Publications

Cannabis is one of the most commonly used substances in the world. However, its effects on human cognition are not yet fully understood. Although the cerebellum has the highest density of cannabinoid receptor type 1 (CB1R) in the human brain, literature on how cannabis use affects cerebellar-dependent learning is sparse. This study examined the effect of chronic cannabis use on sensorimotor adaptation, a cerebellar-mediated task, which has been suggested to depend on endocannabinoid signaling.Chronic cannabis users (n = 27) with no psychiatric comorbidities and healthy, cannabis-naïve controls (n = 25) were evaluated using a visuomotor rotation task. Cannabis users were re-tested after 1 month of abstinence (n = 13) to assess whether initial differences in performance would persist after cessation of use.Cannabis users showed lower adaptation rates compared to controls at the first time point. However, this difference in performance did not persist when participants were retested after one month of abstinence (n = 13). Healthy controls showed attenuated implicit learning in the late phase of the adaptation during re-exposure, which was not present in cannabis users. This explains the lack of between group differences in the second time point and suggests a potential alteration of synaptic plasticity required for cerebellar learning in cannabis users.Overall, our results suggest that chronic cannabis users show alterations in sensorimotor adaptation, likely due to a saturation of the endocannabinoid system after chronic cannabis use.Copyright © 2022 Elsevier Ltd. All rights reserved.

JTD Keywords: Addiction, Cannabis, Cerebellum, Endocannabinoid system, Visuomotor adaptation

Chronic use of cannabis leads to both motor deficits and the downregulation of CB1 receptors (CB1R) in the cerebellum. In turn, cerebellar damage is often related to impairments in motor learning and control. Further, a recent motor learning task that measures cerebellar-dependent adaptation has been shown to distinguish well between healthy subjects and chronic cannabis users. Thus, the deteriorating effects of chronic cannabis use in motor performance point to cerebellar adaptation as a key process to explain such deficits. We review the literature relating chronic cannabis use, the endocannabinoid system in the cerebellum, and different forms of cerebellar-dependent motor learning, to suggest that CB1R downregulation leads to a generalized underestimation and misprocessing of the sensory errors driving synaptic updates in the cerebellar cortex. Further, we test our hypothesis with a computational model performing a motor adaptation task and reproduce the behavioral effect of decreased implicit adaptation that appears to be a sign of chronic cannabis use. Finally, we discuss the potential of our hypothesis to explain similar phenomena related to motor impairments following chronic alcohol dependency. © 2022

JTD Keywords: adaptation, addiction, alcohol-abuse, cerebellum, chronic cannabis use, cognition, deficits, endocannabinoid system, error processing, explicit, modulation, motor learning, release, synaptic plasticity, Adaptation, Adaptation, physiological, Alcoholism, Article, Behavioral science, Cannabinoid 1 receptor, Cannabis, Cannabis addiction, Cerebellum, Cerebellum cortex, Cerebellum disease, Chronic cannabis use, Computer model, Down regulation, Endocannabinoid, Endocannabinoid system, Endocannabinoids, Error processing, Hallucinogens, Human, Humans, Motor dysfunction, Motor learning, Nerve cell plasticity, Nonhuman, Physiology, Psychedelic agent, Purkinje-cells, Regulatory mechanism, Sensation, Sensory dysfunction, Sensory error processing impairment, Synaptic transmission, Task performance

Gene duplications occur in prokaryotic genomes at a detectable frequency. In many instances, the biological function of the duplicates is unknown, and hence, the significance of the presence of multiple copies of these genes remains unclear.; Gene duplications significantly impact the gene repertoires of both eukaryotic and prokaryotic microorganisms. The genomes of pathogenic Escherichia coli strains share a group of duplicated genes whose function is mostly unknown. The irmA gene is one of the duplicates encoded in several pathogenic E. coli strains. The function of its gene product was investigated in the uropathogenic E. coli strain CFT073, which contains a single functional copy. The IrmA protein structure mimics that of human interleukin receptors and likely plays a role during infection. The enteroaggregative E. coli strain 042 contains two functional copies of the irmA gene. In the present work, we investigated their biological roles. The irmA_4509 allele is expressed under several growth conditions. Its expression is modulated by the global regulators OxyR and Hha, with optimal expression at 37 degrees C and under nutritional stress conditions. Expression of the irmA_2244 allele can only be detected when the irmA_4509 allele is knocked out. Differences in the promoter regions of both alleles account for their differential expression. Our results show that under several environmental conditions, the expression of the IrmA protein in strain 042 is dictated by the irmA_4509 allele. The irmA_2244 allele appears to play a backup role to ensure IrmA expression when the irmA_4509 allele loses its function. IMPORTANCE Gene duplications occur in prokaryotic genomes at a detectable frequency. In many instances, the biological function of the duplicates is unknown, and hence, the significance of the presence of multiple copies of these genes remains unclear. In pathogenic E. coli isolates, the irmA gene can be present either as a single copy or in two or more copies. We focused our work on studying why a different pathogenic E. coli strain encodes two functional copies of the irmA gene. We show that under several environmental conditions, one of the alleles dictates IrmA expression, and the second remains silent. The latter allele is only expressed when the former is silenced. The presence of more than one functional copy of the irmA gene in some pathogenic E. coli strains can result in sufficient expression of this virulence factor during the infection process.

JTD Keywords: 042, aec69, enteroaggregative e. coli, gene duplications, 042, Adaptation, Aec69, Aggregative adherence, Chromosomal genes, Coli, Duplication, Enteroaggregative e, Escherichia-coli, Evolution, Gene duplications, Hha/ymoa, Irma, Mechanism, Outer-membrane, Protein

Marine ancestors of freshwater sponges had to undergo a series of physiological adaptations to colonize harsh and heterogeneous limnic environments. Besides reduced salinity, river-lake systems also have calcium concentrations far lower than seawater. Cell adhesion in sponges is mediated by calcium-dependent multivalent self-interactions of sulfated polysaccharide components of membrane-bound proteoglycans named aggregation factors. Cells of marine sponges require seawater average calcium concentration (10 mM) to sustain adhesion promoted by aggregation factors. We demonstrate here that the freshwater sponge Spongilla alba can thrive in a calcium-poor aquatic environment and that their cells are able to aggregate and form primmorphs with calcium concentrations 40-fold lower than that required by marine sponges cells. We also find that their gemmules need calcium and other micronutrients to hatch and generate new sponges. The sulfated polysaccharide purified from S. alba has sulfate content and molecular size notably lower than those from marine sponges. Nuclear magnetic resonance analyses indicated that it is composed of a central backbone of non- and 2-sulfated α- and β-glucose units decorated with branches of α-glucose. Assessments with atomic force microscopy/single-molecule force spectroscopy show that S. alba glucan requires 10-fold less calcium than sulfated polysaccharides from marine sponges to self-interact efficiently. Such an ability to retain multicellular morphology with low environmental calcium must have been a crucial evolutionary step for freshwater sponges to successfully colonize inland waters.

JTD Keywords: Carbohydrate interactions, Evolutionary adaptation, Porifera, Proteoglycans, Sulfated polysaccharides

Background—The cerebellum has been recently suggested as an important player in the addiction brain circuit. Cannabis is one of the most used drugs worldwide, and its long-term effects on the central nervous system are not fully understood. No valid clinical evaluations of cannabis impact on the brain are available today. The cerebellum is expected to be one of the brain structures that are highly affected by prolonged exposure to cannabis, due to its high density in endocannabinoid receptors. We aim to use a motor adaptation paradigm to indirectly assess cerebellar function in chronic cannabis users (CCUs). Methods—We used a visuomotor rotation (VMR) task that probes a putatively-cerebellar implicit motor adaptation process together with the learning and execution of an explicit aiming rule. We conducted a case-control study, recruiting 18 CCUs and 18 age-matched healthy controls. Our main measure was the angular aiming error. Results—Our results show that CCUs have impaired implicit motor adaptation, as they showed a smaller rate of adaptation compared with healthy controls (drift rate: 19.3 +/− 6.8° vs. 27.4 +/− 11.6°; t(26) = −2.1, p = 0.048, Cohen’s d = −0.8, 95% CI = (−1.7, −0.15)). Conclusions—We suggest that a visuomotor rotation task might be the first step towards developing a useful tool for the detection of alterations in implicit learning among cannabis users.

JTD Keywords: Cerebellum, Cannabis, Implicit motor learning, Motor adaptation, Visuomotor rotation