Edgar Garcia-Rill - US grants

Stimulation of the mesencephalic locomotor region (MLR) is known to initiate and maintain walking in the brainstem-transected animal by modulating locomotion oscillators present in the spinal cord. Over the past several years we have applied clsssical neurophysiological and anatomical methods in the locomotion on a treadmill preparation. Our studies have demonstrated the presence of projections from the two main outputs of the basal ganglia, the pallidum and substantia nigra (SN), to the MLR Recent findings revealed the occurrence in MLR neurons, of rhythmic firing patterns related to locomotor movements. These studies established that the pedunculopontine necleus, a known termination sitse of basal ganglia outputs, forms part of the MLR. In addition, the overall anatomical organization of other afferents and of the efferents of the MLR were described in the walking preparation. Significantly, we reported that descending MLR efferents travel via Probst's tract and to the nucleus reticularis gigantocellularis (NRG), a source of reticulospinal projections. Our latest findings provide a significant advance in the application of this preparation, not only as a model for the study of locomotion, but also as a method for investigating chemotherapeutic strategies in the treatment of diseases involving locomotor movements, e.g. Parkinsonism, stroke, trauma. The limitations of stimulation-induced locomotion (fatigability, variability and low yield) now can readily be overcome with the use of chemical-induced locomotion. We have been able to induce locomotion by application of pharmacological substances within the MLR. Our preliminary findings suggest that chemical-induced locomotion is, 1) site specific, i.e. produces locomotion only when application is made within the MLR, 2) transmitter specific, and 3) provides lasting, reproducible walking. The proposed research will take advantage of this development in order to investigate, 1) the chronology and characteristics of rhythms present in MLR, NRG and SN neurons during chemical-induced locomotion, 2) the ability of NRG to induce, or modulate MLR-induced, locomotion, and 3) the ability of the SN to modulate MLR- or NRG-induced locomotion. These studies will provide comprehensive information which should enable the design of an appropriate chemotherapeutic and/or prosthetic control for locomotor events - the ultimate aim of this research.

The proposed research will employ the chronic, adult rat, complete spinal cord transection model of spinal cord injury. The model is clinically relevant, avoids problems posed by developmental (neonatal lesion) models and is well established in our laboratories. Various palliative strategies will be used to determine the possible responses of and changes in several anatomical and physiological measures following spinal cord injury. These strategies include, a) exercise training, b) fetal spinal cord implants into the transection cavity, c) peripheral nerve grafts bridging the transection, and d) neurotrophic factor-containing nitrocellulose strips implanted in conjunction with fetal tissue implants or nerve grafts. The anatomical measures to be carried out include, a) dorsal root axon regrowth, b) immunocytochemical detection of indoleaminergic fiber regrowth, c) fluorescent dye tracing of axonal regrowth via peripheral nerve grafts, and d) hindlimb muscle fiber size and number. These measures are expected to give an indication of the degree of survivability, tissue reconnection and salutary effects of the various strategies described above on neuronal and muscular tissue below the level of the lesion. The physiological measures to be used include, a) H-reflex monitoring, b) locomotion induced in the decerebrate preparation by stimulation of the mesencephalic locomotor region, and c) locomotion induced by stimulation of the lumbar enlargement in the same preparation. These measures are designed to reveal any gradual changes in reflex function as a result of the various palliative measures, and to determine if locomotion or modulation of spinal pattern generator function occurs following such procedures. this program of research is intended to provide a wide range of normative data in a relevant model of spinal cord injury, as well as probe various possibilities for surgical intervention which might lead to functional improvement following spinal cord trauma. Our preliminary findings provide exciting new indications that the proposed palliative strategies might provide a measure of functional restitution.

Lindley The University of Arkansas for Medical Sciences shares with its sister campus, the University of Arkansas at Fayetteville, a major responsibility for life sciences and university-based biotechnology research and development performed for the state of Arkansas. Built in 1957, the Shorey Building, a nine story structure, recently housed all the basic science departments and most of the research laboratories and support facilities. The research space is sub-standard for many aspects of modern cellular and molecular neurobiology, in spite of the fact that they represent essentially the only significant university-based capacity in the state for neurobiology research. Certain core facilities requisite to modern cellular molecular neurobiology, such as adequate darkrooms, tissue culture capabilities and space to house large equipment, are not available. Inadequate infrastructure is a hindrance for the application of contemporary cellular and molecular biology and biophysics to neurobiological problems. The laboratories are a critical success factor for continued development of Arkansas efforts in biotechnology. They also provide research training opportunities for graduate, undergraduate and high school students. ARI funds will be used to support various renovations including: asbestos abatement, upgrading HVAC and electrical power systems, installing new benches and lab islands, modernizing cell and tissue culture and darkroom facilities, and providing a central autoclave and glassware washing facility. Provisions for computer network access and data analysis space will also be included. Once completed, the basic biological research conducted in the renovated facilities will build on and be synergistic with the research program launched by the NSF EPSCoR Arkansas Neurobiology Center. Modernized facilities will enhance the research programs of investigators who contribute to biotechnology linkages and improved scientific training for undergraduates in partn ership with Arkansas institutions, including the historically black colleges, Philander Smith College and the University of Arkansas at Pine Bluff.

The objective of this Program Project is to study and develop multiple, new, synergistic strategies for intervention and rehabilitation after spinal cord injury. The research program is composed of two short-term and two long-term strategies which initially will be pursued independently, but ultimately will be combined to provide optimal synergistic effects. This powerful approach is based on recent advances in developing palliative strategies for spinal cord injury in several of our laboratories using state-of-the-art neurotransplantation, electrophysiological and molecular techniques. Herein, we combine a wealth of interdisciplinary experience focused on a series of interrelated projects, which promise to provide more effective, economical scientific contributions than if pursued separately. The short-term intervention section will address the issues of, 1) compensation of locomotor function using a novel prosthetic device, and 2) the reduction or prevention of muscle atrophy after spinal cord injury. The long-term intervention section will address the issues of, 3) optimizing functional integration of both fetal spinal cord implants and peripheral nerve grafts with the host tissue, and 4) designing intervention strategies based on the phenomenon of critical periods in development which allow functional recovery if damage occurs before, but not after, these specific time points. These four potent approaches have the potential not only for developing independent intervention methodologies, but also for designing a multifaceted approach to spinal cord injury. Therefore, studies are proposed to explore the effects of combining these strategies. We believe that the most desirable treatment strategies at some or all stages of intervention and rehabilitation after spinal cord injury ultimately may include electrical stimulation, neurotransplantation, exercise training and pharmacological modulation. Our team is in a unique and advanced position to lead the development of these strategies.

The objective of this Component is to determine if epidural stimulation of the spinal cord can be used for intervention and rehabilitation of posture and locomotion following spinal cord injury (SCI) in the cat. We have determined that epidural stimulation of the lumbar enlargement (LE) using low frequencies (1-5 Hz) will induce hindlimb stepping soon after complete spinal cord transection at thoracic levels. Higher frequency stimulation (>10Hz) was found to lead to rigidity (antagonist cocontraction) of the hindlimbs (i.e. standing). The proposed studies will determine if epidural LE stimulation can be used to induce locomotion or standing for prolonged periods (weeks or months) following SCI. The ability of pharmacological agents to reduce the electrical threshold, augment the electrical stimulation-induced effects or reinstate locomotion or standing if electrical stimulation is no longer effective, all will be tested. A treadmill training and standing training regimen will be instituted. Since the use of prostheses and/or rehabilitative interventions in the SCI patient may be delayed, we will test the effects of 30 and 90 day waiting periods on the efficacy of epidural LE stimulation-induced locomotion or standing. Finally, we will test the possible additional salutary effects which fetal spinal cord implants made into the injury site will have on electrically- and/or chemically-induced locomotion and standing. We will analyze the changes in the locomotor step cycle and electromyographic measures of standing induced by epidural electrical stimulation and/or pharmacological therapy. In terminal experiments, changes in spinal cord circuitry will be measured using the H-reflex. The force and fatigability of relevant hindlimb muscles in one hindlimb will be tested in order to determine the possible salutary effects of these interventions on muscle function. Muscles in the other hindlimb will be analyzed immunocytochemically for myofiber size changes and the expression of relevant myosin heavy chain isoforms. These results will reveal specific fiber size and type changes effected by the various palliative strategies described. In addition, immunocytochemical labeling of specific transmitter types will be used to detect changes induced by SCI and possible alterations of those changes induced by the interventions described. This comprehensive study will test a promising prosthetic device for its potential to be used exclusively or in combination with pharmacotherapeutic intervention, neurotransplantation and/or training regimens. We will test its ability to reduce the deficits and, perhaps, improve postural, locomotion, reflex and muscular function after SCI.

The purpose of the Image Analysis Core will be to provide centralized image analysis services to each of the Components of the Program Project. Three types of specialized measures will be carried out: muscle fiber size and distribution in Components I, II and IV, density of immunocytochemically labeled spinal cord fiber systems and morphometric reconstruction and analysis of labeled motoneurons in Components I, III and IV. The Core Facility consists of one room (300 sq. ft.) containing two Biographics Image Analysis Workstations. Each workstation consists of a microscope with fluorescence capability and a motorized stage and controller which feeds X,Y and Z coordinates to the computer. Each computer is a 486 with 135 MB hard disk and an external optical disk storage (650 MB each) device. A digitizing tablet with mouse allows inputting of the microscope Image through a drawing tube. Each workstation is capable of morphometric analyses (including area, volume, lengths, branching, etc.), three dimensional reconstruction (line drawings, solid and transparent objects), quantitative densitometry (including quantitative autoradiography, gel density, etc.), frame grabbing (video or photographed images), and various other functions. Data can be displayed on spreadsheet format, graphed format or in color images. Output formats are color photographs or slides, or laser printed images or data. The centralized measurement of muscle fiber size and distribution, immunocytochemically labeled afferent fiber density and reconstruction of labeled cells across Components will allow standardization of results across Components, permitting comparison across paradigms and species. This will free each Component to make the more complex individual analyses proposed.

acupuncture /acupressure; arousal; brain electronic stimulator; electrodes; evoked potentials; brain electrical activity; clinical research; human subject;

DESCRIPTION (provided by applicant): The pedunculopontine nucleus (PPN) helps control sleep-wake rhythms and modulates posture and locomotion. The proposed research will address three functional aspects (ascending, local and descending) of the PPN, the cholinergic arm of the Reticular Activating System (RAS). From 10-30 days postnatally there is a dramatic decrease in the percent of REM sleep in the rat. A hypothesis was proposed suggesting that disturbances in the developmental decrease in REM sleep, a return to a neonatal state of REM sleep drive, could lead to a number of disorders characterized by increased REM sleep drive. We tracked changes in ascending and descending projections from the PPN, along with developmental changes in neurochemical systems modulating the PPN. We found that certain neurotransmitters could be responsible for modulating the developmental decrease in REM sleep, reported new interactions between identified cell types, and proposed a push-pull model for PPN modulation of posture and locomotion. We also discovered the presence of electrical coupling in the PPN as well as in an ascending and a descending target of the PPN. Preliminary evidence suggests that changes in electrical coupling parallel the developmental decrease in REM sleep. This newly discovered mechanism will be explored using a) whole-cell patch clamp and intracellular sharp electrode recordings, b) pharmacological manipulation to induce and block electrical coupling, and c) measures of connexin-36 mRNA expression and protein levels before and during the developmental decrease in REM sleep (7-30 days), in 1) the parafascicular nucleus (Pf), an ascending target of the PPN, 2) the PPN itself, and 3) the SubCoeruleus (SubC) nucleus, a descending target of the PPN implicated in the generation of REM sleep. The discovery of electrical coupling in these RAS nuclei is critical given that recent findings suggest that the stimulant modafinil exercises its effects by increasing electrical coupling. Conversely, a number of anesthetics are known to decrease electrical coupling. The mechanistic characterization proposed represents a new paradigm for sleep-wake control and may revolutionize how we think about sleep-wake control, reveal how electrical coupling interacts with known transmitter inputs in the RAS to modulate sleep-wake states, and how we may develop new therapeutic strategies for the treatment of a number of devastating disorders that have as a common symptom the manifestation of increased REM sleep drive. In fact, by ignoring the role of electrical coupling we will fail to understand this system. We discovered the presence of electrical coupling, by which nerve cells can communicate directly through pores called gap junctions, in the part of the brain that controls sleep-wake cycles, the reticular activating system (RAS). We demonstrated the presence of electrical coupling using recordings from pairs of neurons. This finding helps explain the actions of some anesthetics, which are known to block gap junctions, and of a new stimulant, modafinil, which is now known to increase electrical coupling. This novel mechanism may promote ensemble activity in large numbers of neurons to promote rhythms during waking, and the absence of such activity may lead to sleep. We propose a series of detailed studies to investigate the organization (which cells are coupled, which are not), the control (which transmitter systems activate, which inhibit), and the modulation (which agents can increase vs decrease coupling) of this mechanism. The mechanistic characterization proposed represents a new paradigm for sleep-wake control and may revolutionize how we think about sleep-wake control, reveal how electrical coupling interacts with known transmitter inputs in the RAS to modulate sleep-wake states, and how we may develop new therapeutic strategies for the treatment of a number of devastating disorders that have as a common symptom the manifestation of increased REM sleep drive. In fact, by ignoring the role of electrical coupling we will fail to understand this system.

Although our movements seem smooth and continuous to us, they are not. They are generated by the brain in small steps. This pulsing signal from the brain is reflected in our muscles as what is known as physiological tremor; it occurs at about 10 pulses per second, and it occurs both during movement and rest. This pulsing signal is thought to save time and computational load in the brain, and serves to bring all parts of the motor system into step. The proposed studies will explore the possibility that a crucial part of the brain, the reticular activating system, which helps control sleep-wake cycles and arousal as well as posture and movement, generates this necessary background of activity, all at the same rate of about 10 pulses per second. Such a background of activity could participate in higher processes such as attention as well as lower motor processes such as changes in posture or locomotion. This widespread rhythm might be involved in such complex functions as fight-or-flight responses in which attention (perceiving a threat) and locomotion (fighting or escaping) are coordinated. In this project, higher brain regions involved in attention as well as lower brain regions controlling posture and movement will be studied, in order to determine if the reticular activating system talks to both higher and lower centers in the same fashion. This would explain how we can smoothly carry out complex fight-or-flight responses, and how we can change states, such as from sleeping to waking, and shift our motor system accordingly.

DESCRIPTION (provided by applicant): We will implement a Career Development Program for five Project Principal Investigators (PIs) who are close to nationally competitive levels using grant support and mentoring activities undertaken by established investigators. Each Project involves unique, innovative state-of-the-art research. The goal is to help these PIs secure mentored grants or R01 funding within 1-3 years, replacing them with other investigators close to nationally competitive levels, and helping those investigators secure extramural support. By the end of the award period, our goals are 1) to generate mentored grants and R01 funding for at least seven new investigators, and 2) to secure two additional multi-investigator awards. The Projects chosen have significant synergy, which will facilitate the third goal, 3) the submission of a Program Project application (P01) linking at least three of the new R01 awardees with other established investigators. We will also establish a multi-disciplinary Center for Translational Neuroscience (CTN) that will take advantage of the existing faculty strengths and expand the neuroscience research infrastructure, becoming a hub for campuswide collaborations. The CTN will also benefit from the recruitment of two tenure-track, mid- to senior-level, funded investigators who will also become mentors to Project PIs. In addition, three other faculty of junior rank will be recruited during the life of the award, adding to the critical mass of investigators. Additional potential future PIs will be recruited through a Pilot Study award program. The significant institutional commitment for this effort, will be parlayed into independent extramural support for the Center (P50 award) by the end of the award period. The Director of the CTN has experience with large-scale development programs, Program Project grants and has been Federally funded for over 20 years. We will establish a Core Facility and an Experimental Core, to provide an efficient means of ensuring that sophisticated and expensive instrumentation is fully utilized, maintained and operated by trained professionals. We will ensure that Project PIs have access to state-of-the-art services and facilities (through yearly purchases of new equipment), providing the basic underpinnings of the translational neuroscience research efforts at UAMS.

sensory feedback; arousal; Alzheimer's disease; clinical research; human subject;

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We propose to implement a Career Development Program, a Leadership Program, a multidisciplinary team Project Program with significant synergy, similar Performance Milestones, and will continue our Recruitment Program, and expand our Core Facilities. A. Career Development Program: The approach has been through formal facilitation with structure and accountability rather than natural or situational mentoring. We will continue all five elements of the current Career Development Program that we have found to succeed, and will add two aspects that we believe will improve the program. The new aims include: New Specific Aim 1: Self-assessment. We will test a tool for Mentoring Self-Assessment, with the view towards identifying and adopting the best mentoring practices. This self-assessment tool is included in Appendix #4 and was developed by the University of Pittsburgh. We will perform the self-assessment every six months to track progress. New Specific Aim 2: Mentoring for collaborative research. Our collaborative research mentoring sessions will emphasize, on the one hand, how to establish fruitful collaborations (discuss the usual types of collaborations, samples of collaborative situations, types of agreements, NIH and other agency regulations regarding collaborative research), and, on the other hand, how to design fruitful collaborations (discuss the design of multi-disciplinary research, minimizing barriers to collaborative research, identifying potentially successful or undesirable collaborations). Specific Aim 3: Established Mentor Program: We have had great success in matching established Mentors with research background and expertise appropriate to their respective Mentees. Specific Aim 4: External Speaker Program: Four to six nationally prominent speakers per year, each an expert (and potential advisor or reviewer) in the area of research of each Individual Project will be invited by the Project investigators. Specific Aim 5: Biostatistics and Experimental Design: This program will help the Project investigators with experimental design in the proposed studies and in future applications. It will provide individualized instruction and advice in order to optimize access by the investigators. Specific Aim 6: Grant writing and reviews: The CTN will support the costs of grant writing through the Office of Grants and Scientific Publications at UAMS in order to optimize style and organization. Implicit in our Career Development Plan is our Mentoring Plan, which, in addition to those issues discussed above under Aim 3, involves the choice of compatible Mentors and Mentees to facilitate academic development at the faculty level. In addition, the CTN will institute a Leadership Program that will be a yearlong process designed to go beyond that program specifically with the future of translational neuroscience in mind. Its primary goal is to provide the tools and resources to develop creative leaders who will guide and transform academic services for translational research and higher education in the twenty-first century.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The Experimental Core now has five Core Facilities. The Human Electrophysiology Core Facility undertakes studies related to human midlatency uditory evoked responses as arousal (pre-attentional) measures, attentional measures as exhibited by performance of a Psychomotor Vigilance Task (PVT) reaction time test, cognitive functions as exhibited in the performance of an Operant Test Battery (OTB), and relative frontal lobe blood flow as measured using Near Infrared Spectroscopy (NIRS). The Image Analysis Core was developed during Year 1 of the award and consists of a confocal microscope with fluorescence and image analysis software, along with a high speed camera for visualizing voltage-dependent and calcium dyes in the in vitro recording rig. The Animal Electrophysiology Core has P13 potential and TMS facilities for rats. The Molecular Core has bRT-PCR, Luminex and other assays. The TMS Core has facilities for TMS in humans for a number of disorders.

The CTN Pilot Study Program will duplicate all ofthe proven methods previously used in Phases I and II to determine which investigators are most likely to become independently funded following CTN support. The aims of this program are: Specific Aim 1: Facilitating the generation of preliminary data for submission of novel grant applications by early stage and established investigators. While early stage investigators are targeted for selective development, some awards may be used to support particularly novel research by established individuals, as long as cutting-edge scientific criteria are met. The applications, as was the case for the first set of pilot studies selected (see below), will be reviewed and scored independently by the EAC. Specific Aim 2: Develop novel treatments and improved outcomes for neurological disorders. Given the translational mission ofthe CTN, we are interested in advancing the field of novel therapeutic interventions and improving outcomes, especially of underserved populations, and will target upgrading or expansion of Core Facilities to further this aim. Specific Aim 3: Implement the strategic plan (see Overview) to secure awards clustered around the missions of selected NIH institutes, e.g. NICHD, NINDS, in order to facilitate future P30 support. In order to develop a competitive application for future P30 support, a major requirement by most institutes is the required inclusion of a number of awards, usually at least five from the same institute that will be served by the P30. We have considerable strength in NICHD funding and may soon have a critical mass of awards in order to be competitive for a P30 award from that institute. However, we plan to guide our research by targeting another institute in whose area we some strengths, NINDS. The selection ofthe Pilot Study awards has already been undertaken by the EAC and these projects center on movement disorders. Given a few new awards, we should be competitive for support for a P30 from NINDS as well. The long-term plan, therefore, is to begin gathering the critical mass of awards for at least two P30 applications during the next 3-4 years. Specific Aim 4: Carry out a Program Evaluation of four major portions ofthe CTN, the Mentoring Plan, Leadership Program, Pilot Study Program, and Core Utilization. Data collection forms, interviews, meeting minutes, website database, conference evaluation forms, and satisfaction surveys will be used to evaluate program implementation and outcomes. Responses to evaluations will be drafted for the progress reports to the EAC and lAC. This process will optimize the effectiveness of each of the major elementis of the CTN, with the long-term goals of providing sufficient and convincing information, a) on substantive deviations from the outlined objectives, expected activities, time frames, or outcomes so that corrective actions promptly implemented, and b) facilitating the adoption ofthe program on an institution-wide basis. These aims will cement a foundation for a self-sustaining and successful center that can compete successfully for P30 support.

The Animal Electrophysiology and Imaging Core Facility is the most used of the CTN Cores. It supports several funded projects by CTN investigators, including current ESIs, new recruits, established mentors, and investigators from other state institutions. This Core Facility will be absolutely essential for expanding collaborations throughout the state because it contains state-of-the-art equipment that is unavailable at these state institutions. We expect that a number of Exploratory Research projects will require the facility. The Animal Electrophysiology and Imaging Core Facility is not a standard capability entity, but has always been characterized by the development of innovative technologies and advances in the area. We have developed several novel technologies that allow users to ask much more sophisticated questions than would otherwise be possible, all at lower cost. The one Core allows access to sophisticated electrophysiological methods in vivo and in vitro, as well as visualization of cells and cellular processes that would be difficult to find in a single Core Facility. For example, we helped develop the new standard for patch-clamp recordings using an upright microscope, that has superior optics arid a platform that facilitates patching of up to 4 cells simultaneously. We developed the first system, using an upright microscope that allows visual patching of identified cells as well as recording population responses. This rig uses an interface chamber, which has been used by others for blind patching, but we custom designed a system with epiillumination and epifluorescence that allows an interface chamber to be attached to the platform (instead of a superfusion chamber), along with an industrial 50X objective (used for microchip design and construction), in order to visualize and patch a single cell and record population responses simultaneously. This interface chamber patch-clamp rig has a CMOS (complementary metal-oxide semiconductor) and an EMCCD (charge-coupled device) camera that allows high-speed voltage-sensitive dye imaging as well. We have also applied event related spectral perturbation (ERSP) analysis using MatLab and a high capacity, 4 processor computer to analyze population responses with great success. Our modified immunocytochemical labeling methods of single cells recorded in slices allow us to label the entire 400 um slice instead of needing to cut it into thin sections. This improves the yield and retains the cell within the slice, allowing visualization and three-dimensional reconstruction of the cell within the population at large. Perhaps most significant is our development of calcium imaging technology. By using two high-speed cameras, we can perform ratiometric sampling as fast as 2 KHz. This permits the visualization, for example, of single channel calcium oscillations in the gamma band range. An additional advantage of this Gore is a freely-moving animal evoked potential rig for startle response and evoked potentials, especially PI 3 potential recordings, the rodent equivalent of the human P50 potential, allowing parallel animal and human studies. For example, we have ongoing projects using TMS and P50 potential recordings in humans in the Human Electrophysiology Core, and parallel studies using TMS and the PI 3 potential in rodents in vivo. This Core has a fully equipped surgical suite for survival surgeries and implantation of electrodes and pumps. A separate electrophysiology rig measures cutaneous and H-reflexes, and contains 2 treadmills and 8 motorized bicycle exercise trainers for recovery from injury or disease. These are used in ongoing studies on spinal cord injury arid Amyotrophic Lateral Sclerosis.

Advisory Committees; Biometry; career; career development; Core Facility; Department chair; design; experience; Grant; Human; Individual; Leadership; Mentors; Modeling; Neurosciences Research; operation; Performance; Pilot Projects; Program Development; programs; Research; Research Personnel; Self Assessment; Series; Teacher Professional Development; translational neuroscience; United States National Institutes of Health; Writing;