NIMH Instrumentation Core Facility

Dold, George

Abstract

This past year, our Section had the unique opportunity to support the research of various Labs & Sections within NIMH, NINDS, NICHD, and NCCIH. During the past twelve months, investigators from these labs and branches requested 467 formal projects from our staff. Each of these requests was documented and the time recorded to complete the job. In addition to the formal requests we are available daily for numerous walk-in, phone call or e-mail requests for assistance. In general, our technical support this past year can be divided into the following research areas: Electrophysiology The Section on Instrumentation (SI) staff continuously strives to improve the utility of various components that comprise electrophysiology. We have continued to improve the engineering and fabrication of multiple-hole grid arrays that allow precise, repeatable placement of a single or multiple electrodes over a wide area. We have also continued to develop small single-electrode microdrives. Novel methods using 3D printing now allow for the production low-component count yet accurate and smooth microdrives. In FY2018, SI supported a project that will allow the placement of 120 electrodes in each of four anatomically interconnected deep brain areas. This requires developing tiny electrode manipulators that will be permanently mounted on a custom platform fixed to the skull. It requires developing methods to use MRI-guided positioning at the four deep targets by custom fitting the platform to an individual using a combination of MRI, CAT scan, and 3D mechanical models. It requires a superstructure to support 480 connections in 15 high-density connectors. The platform, microdrives and superstructure must be MRI compatible. The final design will use a mixture of 3D printing of plastics, including biocompatible plastic, a mix of brass and stainless-steel hardware and 3D printing of a titanium superstructure. fMRI SI provides a wide range of support for fMRI-related research. Fabrication of devices for use in MRI environments is a specialized area of expertise, with great attention given to design without ferrous metals and minimization of all metal components. In addition, commercial industrial fiber optic components and systems are evaluated and integrated into many designs and devices we fabricate. The Section on Instrumentation supports the installation of new equipment in MRI suites, including custom mirror and projection assemblies used for stimulus presentation, and custom RF-shielded penetration panels used to route cabling. Non-Human Primate (NHP) SI is responsible for providing a wide range of engineering and fabrication services to support non-human primate research. Many of the mechanical assemblies that are necessary for this type of research are engineered and fabricated in-house. Our group provides a diverse array of custom systems and components to many different investigators, such as custom primate chairs, high-strength restraints, MRI positioning systems, custom head coils, reward systems, data acquisition, analysis and optical response systems, plus a wide range of small mechanical components. To facilitate the social housing and welfare of animals, caging systems have been modified by SI to permit larger social groups and further enrich the environment. In addition, unique nesting and transfer boxes have been designed and constructed to attach to the caging systems to facilitate animal transfers and normal nesting behavior. Human Human research requires the creation of many novel devices that are compatible with the high-magnetic field environment. When a new magnet is installed, we are consulted with and provide the necessary components for presenting visual stimuli in the bore of the magnet, including image periscopes, screens, and mirrors. These devices are designed and manufactured with specific space and material constraints. Behavioral Several different types of mazes are used to study spatial learning and memory in rodents. These studies have been used to help understand general principles about learning that can be applied to humans, and to determine how different treatments affect learning and memory. We continue to produce a variety of custom T and Y mazes for behavioral testing. One particular task is known as the delayed non-match-to-sample task. Each trial in this task consists of three periods the sample, delay and choice periods. Trials begin by the mouse sampling a maze arm. Mice must then maintain a memory of the sampled maze arm across a delay period, and use this memory in the choice period to correctly choose the opposite maze arm to receive a reward. The sample arm location is randomized every trial so that correct performance is only guided by information encoded in the most recent sample period, hence why this task is a measure of working memory. T-mazes are used to assess the neural circuits that support normal working memory function, and how these circuits fail in mouse models of predisposition to psychiatric disease. Imaging Two-photon excitation microscopy is a fluorescence imaging technique that allows imaging of living tissue up to about one millimeter in depth. Two-photon excitation can be a superior alternative to confocal microscopy due to its deeper tissue penetration, efficient light detection, and reduced phototoxicity. SI produces a variety of equipment that supports two-photon microscopy, such as faraday cages for electronic and light shielding and custom mirror mounts, behavioral testing equipment such as low-inertia running wheels, and custom titanium headposts. SI fabricated a laser path enclosing box and microscope path light blocking box that allowed the combining of two-photon imaging of GCaMP6f and local field potential recordings in behaving mice. In order to decipher circuit mechanisms for corticocortical communication, we produced a custom multi-amplitude and variable frequency whisker stimulator. Clinical Our Section also supports a number of clinical based research requests under the broad areas of surgical, therapeutic and basic research. SI continued its development on the Gustometer system for obesity studies. The purpose of this study is to investigate the areas of the brain using fMRI that respond to gustatory stimuli. We developed an MRI compatible system that delivers specified small volumes of a variety of tastants into a patients mouth while being scanned in the MRI. The tastants are released in a pre-programmed fashion under computer control, and the delivery of the tastants is synchronized with the scan pulse from the MRI unit. The entire fluid delivery system is pneumatically controlled powered by house medical air that has been precisely regulated to either operate the control valves or pressurize the syringes containing the tastants. The control valves are operated automatically by a computer running LabVIEW (National Instruments) software with the requisite input/output electronics. Technology Technology By using the latest technology in advanced fabrication machinery, we are able to increase productivity and effectiveness while at the same time decreasing the amount of time needed to engineer and machine the components. Our waterjet cutter continues to increase our cutting and fabricating capabilities, especially with the multiple fiberglass parts we produce. With this system, we were able to fabricate miniature titanium headposts that would have been very difficult to machine with conventional tooling.