Faculty Bibliography

Recent experiments have shown that mouse primary visual cortex (V1) is very different from that of cat or monkey, including response properties-one of which is that contrast invariance in the orientation selectivity (OS) of the neurons' firing rates is replaced in mouse with contrast-dependent sharpening (broadening) of OS in excitatory (inhibitory) neurons. These differences indicate a different circuit design for mouse V1 than that of cat or monkey. Here we develop a large-scale computational model of an effective input layer of mouse V1. Constrained by experiment data, the model successfully reproduces experimentally observed response properties-for example, distributions of firing rates, orientation tuning widths, and response modulations of simple and complex neurons, including the contrast dependence of orientation tuning curves. Analysis of the model shows that strong feedback inhibition and strong orientation-preferential cortical excitation to the excitatory population are the predominant mechanisms underlying the contrast-sharpening of OS in excitatory neurons, while the contrast-broadening of OS in inhibitory neurons results from a strong but nonpreferential cortical excitation to these inhibitory neurons, with the resulting contrast-broadened inhibition producing a secondary enhancement on the contrast-sharpened OS of excitatory neurons. Finally, based on these mechanisms, we show that adjusting the detailed balances between the predominant mechanisms can lead to contrast invariance-providing insights for future studies on contrast dependence (invariance).

Common data elements (CDEs) are becoming more common as more areas of preclinical research have generated CDEs. Herein we provide an overview of the progress to date in generating CDEs for preclinical epilepsy research. Currently there are CDEs that have been developed for Physiology (in vivo), Behavior, Pharmacology, and Electroencephalography (EEG). Together the CDEs and methodologic considerations associated with these CDEs are laid out in consecutive manuscripts published in Epilepsia Open, each describing CDEs for their respective topic area. In addition to the overview of progress for the 4 subjects, core characteristics (Core CDEs) are described and explained. Data collection using a case report form (CRF) is described, and considerations that are involved in using the CDEs and CRFs are discussed.

While most processes in biology are highly deterministic, stochastic mechanisms are sometimes used to increase cellular diversity. In human and Drosophila eyes, photoreceptors sensitive to different wavelengths of light are distributed in stochastic patterns, and one such patterning system has been analyzed in detail in the Drosophila retina. Interestingly, some species in the dipteran family Dolichopodidae (the "long legged" flies, or "Doli") instead exhibit highly orderly deterministic eye patterns. In these species, alternating columns of ommatidia (unit eyes) produce corneal lenses of different colors. Occasional perturbations in some individuals disrupt the regular columns in a way that suggests that patterning occurs via a posterior-to-anterior signaling relay during development, and that specification follows a local, cellular-automaton-like rule. We hypothesize that the regulatory mechanisms that pattern the eye are largely conserved among flies and that the difference between unordered Drosophila and ordered dolichopodid eyes can be explained in terms of relative strengths of signaling interactions rather than a rewiring of the regulatory network itself. We present a simple stochastic model that is capable of explaining both the stochastic Drosophila eye and the striped pattern of Dolichopodidae eyes and thereby characterize the least number of underlying developmental rules necessary to produce both stochastic and deterministic patterns. We show that only small changes to model parameters are needed to also reproduce intermediate, semi-random patterns observed in another Doli species, and quantification of ommatidial distributions in these eyes suggests that their patterning follows similar rules.

The increase of oligomeric amyloid-beta (oAβ) has been related to synaptic dysfunction, thought to be the earliest event in Alzheimer's disease pathophysiology. Conversely, the suppression of endogenous Aβ impaired synaptic plasticity and memory, suggesting that the peptide is needed in the healthy brain. However, different species, aggregation forms and concentrations of Aβ might differently influence synaptic function/dysfunction. Here, we have tested the contribution of monomeric and oligomeric Aβ42 and Aβ40 at 200 nM and 200 pM concentrations on hippocampal long-term potentiation and spatial memory. We found that, when at 200 nM, oAβ40, oAβ42, and monomeric Aβ42 impaired long-term potentiation and memory, whereas only oAβ42 200 pM enhanced synaptic plasticity and memory and rescued the detrimental effect due to depletion of endogenous Aβ. Interestingly, quantification of monomer-like and oligomer-like species carried out by transmission electron microscopy revealed an increase of the monomer/oligomer ratio in the oAβ42 200 pM preparation, suggesting that the content of monomers and oligomers depends on the final concentration of the solution.

PURPOSE/OBJECTIVE:profiles in the longitudinal (z) direction and allow for next-nearest neighbor decoupling. METHODS:Two cylindrical 8-channel arrays having the same length and diameter, 1 of triangular coils and the other of rectangular coils, were constructed and compared in phantom imaging experiments using measures of excitation distribution for a variety of RF shim settings and geometry factor maps for different accelerations on different planes. RESULTS:Coupling between elements was -20 dB or better for all triangular coil pairs, but worse than -12 dB for several of the rectangular coil pairs. Both coils could produce adequate shims on a central transverse plane, but the same shim produced worse results off center for the triangular coil array than for the rectangular coil array. Compared to the rectangular coil array, the maximum geometry factor for the triangular coil array was reduced by a factor of 13.1 when using a 2-fold acceleration in the z-direction. CONCLUSION/CONCLUSIONS:profiles along the z-direction, although this also means that individual slices must be shimmed separately. This design is well suited for parallel transmit applications while also having high receive sensitivity.

OBJECTIVES/OBJECTIVE:To determine whether use of a stylus user input device (UID) would be superior to a mouse for CMR segmentation. METHODS:Twenty-five consecutive clinical cardiac magnetic resonance (CMR) examinations were selected. Image analysis was independently performed by four observers. Manual tracing of left (LV) and right (RV) ventricular endocardial contours was performed twice in 10 randomly assigned sessions, each session using only one UID. Segmentation time and the ventricular function variables were recorded. The mean segmentation time and time reduction were calculated for each method. Intraclass correlation coefficients (ICC) and Bland-Altman plots of function variables were used to assess intra- and interobserver variability and agreement between methods. Observers completed a Likert-type questionnaire. RESULTS:The mean segmentation time (in seconds) was significantly less with the stylus compared to the mouse, averaging 206±108 versus 308±125 (p<0.001) and 225±140 versus 353±162 (p<0.001) for LV and RV segmentation, respectively. The intra- and interobserver agreement rates were excellent (ICC≥0.75) regardless of the UID. There was an excellent agreement between measurements derived from manual segmentation using different UIDs (ICC≥0.75), with few exceptions. Observers preferred the stylus. CONCLUSION/CONCLUSIONS:The study shows a significant reduction in segmentation time using the stylus, a subjective preference, and excellent agreement between the methods. KEY POINTS/CONCLUSIONS:• Using a stylus for MRI ventricular segmentation is faster compared to mouse • A stylus is easier to use and results in less fatigue • There is excellent agreement between stylus and mouse UIDs.

OBJECTIVE:In the context of the current opioid epidemic, there has been a renewed interest in the use of ketamine as an analgesic agent. METHODS:We have reviewed ketamine analgesia. RESULTS:Ketamine is well-known as an antagonist for N-methyl-D-aspartate receptors. In addition, it can regulate the function of opioid receptors and sodium channels. Ketamine also increases signaling through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. These myriad of molecular and cellular mechanisms are responsible for a number of pharmacological functions including pain relief and mood regulation. Clinically, a number of studies have investigated the role of ketamine in the setting of acute and chronic pain, and there is evidence that ketamine can provide analgesia in a variety of pain syndromes. DISCUSSION/CONCLUSIONS:In this review, we have examined basic mechanisms of ketamine and its current clinical use as well as potential novel use in pain management.