Beyond responsible conduct: taking responsibility for the responsible conduct of others.

A unique Responsible Conduct of Research (RCR) course was created for Ph.D., M.D., and M.D./Ph.D. postdoctoral fellows and junior faculty at Northwestern University, some of whom had prior RCR training and some of whom did not. The unique feature of the course is its dual focus on learning the core elements of RCR and preparing participants for being responsible for guiding and monitoring RCR behaviors of others. These more advanced but still junior scientists are at a key junction where they are beginning to mentor and supervise others. A second unique element is a required conversation on at least two RCR topics with their current mentors, with a short written report, modeling explicit conversations about RCR prospectively. Overall response has been very positive with a high level of engagement. Formal and informal evaluation feedback reveals how participants see the value of the course and how it has shaped how they intend to guide others in the future. An important goal of the course is to also position high quality RCR and RCR training within the research environment, not just the classroom.

Translational neural engineering: multiple perspectives on bringing benchtop research into the clinical domain.

A half-day forum to address a wide range of issues related to translational neural engineering was conducted at the annual meeting of the Biomedical Engineering Society. Successful practitioners of translational neural engineering from academics, clinical medicine and industry were invited to share a diversity of perspectives and experiences on the translational process. The forum was targeted towards traditional academic researchers who may be interested in the expanded funding opportunities available for translational research that emphasizes product commercialization and clinical implementation. The seminar was funded by the NIH with support from the Rehabilitation Institute of Chicago. We report here a summary of the speaker viewpoints with particular focus on extracting successful strategies for engaging in or conducting translational neural engineering research. Daryl Kipke, PhD, (Department of Biomedical Engineering at the University of Michigan) and Molly Shoichet, PhD, (Department of Chemical Engineering at the University of Toronto) gave details of their extensive experience with product commercialization while holding primary appointments in academic departments. They both encouraged strong clinical input at very early stages of research. Neurosurgeon Fady Charbel, MD, (Department of Neurosurgery at the University of Illinois at Chicago) discussed his role in product commercialization as a clinician. Todd Kuiken, MD, PhD, (Director of the Neural Engineering for Artificial Limbs at the Rehabilitation Institute of Chicago, affiliated with Northwestern University) also a clinician, described a model of translational engineering that emphasized the development of clinically relevant technology, without a strong commercialization imperative. The clinicians emphasized the importance of communicating effectively with engineers. Representing commercial neural engineering was Doug Sheffield, PhD, (Director of New Technology at Vertis Neuroscience, Inc.) who strongly encouraged open industrial-academic partnerships as an efficient path forward in the translational process. Joe Pancrazio, PhD, a Program Director at NIH's National Institute of Neurological Disorders and Stroke, emphasized that NIH funding for translational research was aimed at breaking down scientific barriers to clinic entrance. Vivian Weil, PhD, (Director of Center for the Study of Ethics in the Professions at the Illinois Institute of Technology) a specialist on ethics in science and engineering, spoke of the usefulness of developing a code of ethics for addressing ethical aspects of translation from the bench to clinical implementation and of translation across disciplines in multi-disciplinary projects. Finally, the patient perspective was represented by Mr Jesse Sullivan. A double-arm amputee and patient of Dr Kuiken's, Mr Sullivan demonstrated the critically important role of the patient in successful translational neural engineering research.

Functionally intact glutamate-mediated signaling in bipolar cells of the TRKB knockout mouse retina.

In the juvenile trkB knockout (trkB-/-) mouse, retina synaptic communication from rods to bipolar cells is severely compromised as evidenced by a complete absence of electroretinogram (ERG) b-wave, even though the inner retina appears anatomically normal (Rohrer et al., 1999). Since it is well known that the b-wave reflects light-dependent synaptic activation of ON bipolar cells via their metabotropic glutamate receptor, mGluR6, we sought to analyze the anatomical and functional integrity of the glutamatergic synapses at these and other bipolar cells in the trkB(-/-) mouse. Although rod bipolar cells from wild-type juvenile mice were determined to be immunopositive for trkB, postsynaptic metabotropic and ionotropic glutamate receptor-mediated pathways in ON and OFF bipolar cells were found to be functionally intact, based on patch electrode recordings, using brief applications ("puffs") of glutamate or its analog, 2-amino-4-phosphonobutyric acid (APB), a selective agonist for mGluR6 receptors. Ionotropic glutamate receptor function was assayed in OFF-cone bipolar and horizontal cells by applying exogenous glutamatergic agonists in the presence of the channel-permeant guanidinium analogue, 1-amino-4-guanidobutane (AGB). Electron-microscopic analysis revealed that the ribbon synapses between rods and postsynaptic rod bipolar and horizontal cells were formed at the appropriate age and appear to be structurally intact, and immunohistochemical analysis did not detect profound defects in the expression of excitatory amino acid transporters involved in glutamate clearance from the synaptic cleft. These data indicate that there does not appear to be evidence for postsynaptic deficits in glutamatergic signaling in the ON and OFF bipolar cells of mice lacking trkB.