The neuromodulatory endocannabinoid system is a promising target for therapeutic interventions. One of well-known behavioral effects of cannabinoid CB1 receptor activation with exogenous ligands such as THC is the inhibition of locomotor activity. However, the behavioral effects of endogenous cannabinoids have not been extensively studied. Despite broad medicinal and recreational use of cannabinoids, little is known about their effects on fine movements, critical for therapeutic applications. Such fine motor function is only resolvable with the precision of marker-based motion capture, which so far has not been available in freely moving mice. Therefore, we have adapted a high-speed, high-resolution marker-based 3D motion capture system to track movement (3D trajectories and speed of markers) during voluntary locomotor tasks in mice. Here we show that enhancing endocannabinoid signaling produces bidirectional effects on locomotor behavior that differ from those caused by exogenous cannabinoid receptor agonist, in unrestricted mice. Given our expectation of subtle rather than dramatic changes with the low and potentially therapeutic doses, we employed a sensitive and accurate marker-based 3D motion capture system to resolve the finest differences in full-body kinematic signatures of mice exploring horizontal and vertical environments. We found that selective upregulation of either of the two main endocannabinoids 2-arachidonoylglycerol (2-AG) or anandamide (AEA) with selective inhibitors of their degradation (MJN110 and PF3845, respectively), produced opposite effects: PF3845 suppressed locomotor activity whereas MJN110 enhanced it. Furthermore, while low doses of the synthetic cannabinoid agonist CP55,940 decreased locomotion in a an open field exploration task as expected, it surprisingly did not affect performance in a vertical climbing task. The results show that the effects of cannabinoid signaling on behavior are not predominantly inhibitory as commonly assumed. Furthermore, we found that the invariant microstructure of locomotory behavior remains unchanged under all treatments, pointing towards motivational rather than motor-related mechanisms of action.

Inferior olive (IO), a nucleus in the ventral medulla, is the only source of climbing fibers that form one of the two input pathways entering the cerebellum. IO has long been proposed to be crucial for motor control and its activity is currently considered to be at the center of many hypotheses of both motor and cognitive functions of the cerebellum.While its physiology and function have been relatively well studied on single-cell level in vitro, presently there are no reports on the organization of the IO network activity in living animals. This is largely due to the extremely challenging anatomical location of the IO, making it difficult to subject to conventional fluorescent imaging methods, where an optic path must be created through the entire brain located dorsally to the region of interest.Here we describe an alternative method for obtaining state-of-the-art -level calcium imaging data from the IO network. The method takes advantage of the extreme ventral location of the IO and involves a surgical procedure for inserting a gradientrefractive index (GRIN) lens through the neck viscera to come into contact with the ventral surface of the calcium sensor GCaMP6s-expressing IO in anesthetized mice.A representative calcium imaging recording is shown to demonstrate the feasibility to record IO neuron activity after the surgery. While this is a non-survival surgery and the recordings must be conducted under anesthesia, it avoids damage to life-critical brainstem nuclei and allows conducting large variety of experiments investigating spatiotemporal activity patterns and input integration in the IO. This procedure with modifications could be used for recordings in other, adjacent regions of the ventral brainstem.

The main purpose of this study is to establish radiation-safe scanning of passersby at high security areas, such as airports and customs. The stomach was selected as the organ to be analyzed. In order to determine whether a substance found inside a human body as wrapped in a plastic bag is filled narcotics or not, many substances in white powder form including morphine-HCL were inspected. Inspection was carried out with on-ionizing radiation by irradiating stomach tissue with laser light. Optical transmittance of lamb stomach tissue was analyzed at different wavelengths. We showed that detection by 650-nm diode laser irradiation would be suitable for such a radiation-safe scan. Different materials were also investigated for absorptive properties, and closed system Raman studies were performed. The spectrum of a molecule found inside white powder placed behind the lamb stomach tissue was detected as a fingerprint. This allowed the detection of target substances without any physical contact or damage to the biological tissue.

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