Cannabis Terpenes Synergistically Modulate Hippocampal Excitability

This work demonstrates how commonly ingested aromatic compounds (terpenes, flavonoids, and odorants) can induce physiological changes on the molecular level in brain regions implicated in high order information processing. Indeed, the component discussed in this study (BCP) is found in relatively high concentrations in common household spices such as cloves and black pepper. Also, limonene is commonly found in the rinds of citrus fruits (e.g. lemon and oranges). These physiological actions could be responsible for individual preferences of different types of foods and aromas that act synergistically with our bodies and modify behavior. Lastly, the need for effective treatments for severe pharmacoresistant forms of pediatric epilepsies such as Dravet syndrome is of imminent importance. Due to current drug laws, it is legally and financially impractical for many people to obtain high quality and high concentration C. sativa extracts. This could lead to ingestion of inferior products with chemical contamination or highly variable concentrations of chemical components. This issue may be completely circumvented by using natural non-cannabis derived cannabinoid agonists. The only limitation is our lack of knowledge and testing regarding these substances.Biology and Biochemistry, Department o

Three-Dimensional GPU-Accelerated Active Contours for Automated Localization of Cells in Large Images

Cell segmentation in microscopy is a challenging problem, since cells are often asymmetric and densely packed. This becomes particularly challenging for extremely large images, since manual intervention and processing time can make segmentation intractable. In this paper, we present an efficient and highly parallel formulation for symmetric three-dimensional (3D) contour evolution that extends previous work on fast two-dimensional active contours. We provide a formulation for optimization on 3D images, as well as a strategy for accelerating computation on consumer graphics hardware. The proposed software takes advantage of Monte-Carlo sampling schemes in order to speed up convergence and reduce thread divergence. Experimental results show that this method provides superior performance for large 2D and 3D cell segmentation tasks when compared to existing methods on large 3D brain images

Analyzing and Modeling the Dysfunction of Inhibitory Neurons in Alzheimer’s Disease

Alzheimer’s disease (AD) is characterized by the abnormal proteolytic processing of amyloid precursor protein, resulting in increased production of a self-aggregating form of beta amyloid (Aβ). Several lines of work on AD patients and transgenic mice with high Aβ levels exhibit altered rhythmicity, aberrant neuronal network activity and hyperexcitability reflected in clusters of hyperactive neurons, and spontaneous epileptic activity. Recent studies highlight that abnormal accumulation of Aβ changes intrinsic properties of inhibitory neurons, which is one of the main reasons underlying the impaired network activity. However, specific cellular mechanisms leading to interneuronal dysfunction are not completely understood. Using extended Hodgkin-Huxley (HH) formalism in conjunction with patch-clamp experiments, we investigate the mechanisms leading to the impaired activity of interneurons. Our detailed analysis indicates that increased Na+ leak explains several observations in inhibitory neurons, including their failure to reliably produce action potentials, smaller action potential amplitude, increased resting membrane potential, and higher membrane depolarization in response to a range of stimuli in a model of APPSWE/PSEN1DeltaE9 (APdE9) AD mice as compared to age-matched control mice. While increasing the conductance of hyperpolarization activated cyclic nucleotide-gated (HCN) ion channel could account for most of the observations, the extent of increase required to reproduce these observations render such changes unrealistic. Furthermore, increasing the conductance of HCN does not account for the observed changes in depolarizability of interneurons from APdE9 mice as compared to those from NTG mice. None of the other pathways tested could lead to all observations about interneuronal dysfunction. Thus we conclude that upregulated sodium leak is the most likely source of impaired interneuronal function

Interneurons from NTG mice exhibit action potentials with significantly higher mean amplitude as a function of stimulus strength as compared to those from APdE9 mice.

<p>Change in mean amplitude of all spikes in the time trace as a function of stimulus strength as we vary (a), <i>G</i>_<i>h</i> (b), and (c). Symbols and lines represent experimental and theoretical values respectively. Squares and triangles are for interneurons from NTG and APdE9 mice respectively. Error bars represent the root mean squared error.</p

Interneurons from APdE9 mice are more depolarized in response to external stimulation as compared to interneurons from NTG mice.

<p>Membrane potential of interneurons during the last 200 ms window of the 500 ms long stimulus after removing the spikes in interneurons from the model as we change <i>G</i>_<i>h</i> (a) and (b) (lines). Observed values for interneurons from NTG (squares) and APdE9 mice (triangles) are shown for comparison. (c) and (d) are from the same simulations as (a) and (b) respectively except that here we show the ratio of depolarization in interneurons from NTG mice to those from APdE9 mice as a function of stimulus strength (lines and symbols are from the model and experiment respectively).</p