Endocannabinoid-Dependent Long-Term Depression of Ventral Tegmental Area GABA Neurons

GABA neurons in the ventral tegmental area of the midbrain are important components in the brain\u27s reward circuit. Long term changes in this circuit occur through the process of synaptic plasticity. It has been shown that high frequency stimulation, as well as treatment with endocannabinoids, can cause GABA neurons in the ventral tegmental area to undergo long term depression, a form of synaptic plasticity that decreases excitability of cells. The present study elaborates on the mechanism whereby high frequency stimulation can result in long term depression of ventral tegmental area GABA neurons. Using the whole cell patch clamp technique in acute brain slices, we recorded excitatory currents from ventral tegmental area GABA neurons in GAD-GFP expressing CD1 mice and observed how the excitatory currents changed in response to different treatments. We confirm that high frequency stimulation causes long term depression, and the cannabinoid type 1 receptor antagonist AM-251 blocks this effect. Long term depression is also elicited by treatment with the cannabinoid type 1 receptor agonist 2-arachidonylglycerol. It is inconclusive whether treatment with 2-arachidonylglycerol occludes further long term depression by high frequency stimulation. We also demonstrate that activation of group I metabotropic glutamate receptors by DHPG produces long term depression. These results support the model that at these excitatory synapses, high frequency stimulation causes the release of glutamate from presynaptic terminals, activating group I metabotropic glutamate receptors, causing production of 2-arachidonylglycerol. 2-arachidonylglycerol in turn acts on presynaptic cannabinoid type 1 receptors to decrease release of glutamate onto GABA neurons. This model can be tested by further research, which should include cannabinoid type 1 receptor knockout mice. This study provides more insight into how drugs of abuse such as tetrahydrocannabinol, the active component of marijuana that activate cannabinoid type I receptors, can corrupt the natural reward mechanisms of the brain

Synaptic Plasticity in the Rodent Hippocampus Involvement of TRPV1 in Plasticity of Area CA1

The hippocampus is the area of the brain where long-term declarative memories are formed. Synaptic plasticity, the long-term strengthening or weakening of the synapse (the connection between two neurons), is the proposed cellular mechanism for the process of memory formation. The two types of synaptic plasticity are long-term potentiation (LTP), in which a synapse becomes strengthened; and long-term depression (LTD), in which a synapse becomes weakened

Initial Experience Using 3-Dimensional Printed Models for Head and Neck Reconstruction in Haiti.

This report describes the first use of a novel workflow for in-house computer-aided design (CAD) for application in a resource-limited surgical outreach setting. Preoperative computed tomography imaging obtained locally in Haiti was used to produce rapid-prototyped 3-dimensional (3D) mandibular models for 2 patients with large ameloblastomas. Models were used for patient consent, surgical education, and surgical planning. Computer-aided design and 3D models have the potential to significantly aid the process of complex surgery in the outreach setting by aiding in surgical consent and education, in addition to expected surgical applications of improved anatomic reconstruction

Prevalence of diabetic retinopathy and self-reported barriers to eye care among patients with diabetes in the emergency department: the diabetic retinopathy screening in the emergency department (DRS-ED) study

Abstract Background Screening for diabetic retinopathy (DR) is suboptimal, and patients with diabetes who present to the emergency department (ED) may be at particularly high risk of undiagnosed DR. The purpose of this study is to determine the prevalence of DR among diabetic patients who present to the ED of our tertiary medical center using teleophthalmology and to assess self-reported barriers to eye care. Methods This cross-sectional, single-institution study recruited clinically stable diabetic patients who presented to the ED during daytime hours over 29 total weekdays across 2 months in 2018 and 2019. Participants had nonmydriatic, 45-degree, single-field digital retinal photographs taken on site (Digital Retinal System, Centervue). Following retinal imaging, participants then completed a survey about barriers to regular eye care and their acceptance of potential interventions to promote screening. Digital retinal photographs were interpreted remotely by a board-certified ophthalmologist and communicated to participants’ primary care physician and/or endocrinologist. Results Over the study period, 275 ED patients had a documented diagnosis of diabetes, of whom 167 were deemed clinically stable for the study and 141 were invited to participate. Sixty-four were enrolled, of whom 50 had gradable-quality fundus images (78%). Of these 50 patients, almost all had type 2 diabetes (47, 94%), with an average disease duration of 12 ± 9 years and mean hemoglobin A1c of 8.1 ± 2.0% (mmol/mol). Based on fundus photography, 14 patients (28%) were diagnosed with DR, which was newly diagnosed for 10 (20% of the total study population). Severity was most commonly mild or moderate (12/14, 86%), with 1 case of severe nonproliferative DR and 1 proliferative DR. The majority (26, 52%) reported at least one barrier to routine eye care in our self-administered survey, of which having too many appointments (6, 12%) and cost (5, 10%) were frequently cited as most important. The majority were receptive to interventions to promote DR screening, including reminder phone calls (29, 58%) and text messages (28, 56%). Conclusions Digital fundus photography in the ED detected a high rate of undiagnosed DR. Half of participants reported barriers to routine care, and most were receptive to messaging interventions to schedule an eye exam. Future studies are warranted to assess scalability of ED-based screening programs and their follow-through rates. </jats:sec

Initial Experience Using 3-Dimensional Printed Models for Head and Neck Reconstruction in Haiti

This report describes the first use of a novel workflow for in-house computer-aided design (CAD) for application in a resource-limited surgical outreach setting. Preoperative computed tomography imaging obtained locally in Haiti was used to produce rapid-prototyped 3-dimensional (3D) mandibular models for 2 patients with large ameloblastomas. Models were used for patient consent, surgical education, and surgical planning. Computer-aided design and 3D models have the potential to significantly aid the process of complex surgery in the outreach setting by aiding in surgical consent and education, in addition to expected surgical applications of improved anatomic reconstruction. </jats:p