The proposed research will test the novel hypothesis that enhanced blood supply to a local brain region impacts neural processing. A key feature of neural circuits is their flexibility, their ability to respond differently (for example, to a sensory stimulus) depending on context. This flexibility allows organisms in general and humans in particular to perform crucial tasks for survival, such as shifting attention. This flexibility is also crucial to brain health: Failures in normal mechanisms of neural dynamics?in the normal ability to shift sensitivity?have been implicated in diseases ranging from epilepsy to schizophrenia.
In this project the PIs will test the prediction that changes in blood supply to cortical sensory neurons can modulate their responses to sensory inputs. To test this hypothesis, they will integrate four techniques, bringing together expertise from two laboratories: whole animal electrophysiological and imaging studies to define the effect of changes in blood flow on neural activity and electrophysiological and imaging studies in brain slices to begin to investigate the mechanisms underlying this phenomenon. A key feature of the proposed research is development of a novel means of bidirectional blood flow regulation, the viral transfection of light-activated channels into smooth muscle. By constricting or relaxing smooth muscles using directed light, they will expand or contract local cerebral arterioles, regulating blood supply. This method provides an approach independent of the potential confounds of pharmacological intervention.
A second key feature of the proposed research is a summer research initiative for Queens College students at MIT. This program will provide a unique opportunity for Queens College students to experience the MIT environment, systematic training in research proposal development, execution of this plan, training in research ethics, and writing a summary for publication.
We have achieved our scientific aim which was to create an in vitro model for regulating blood vessel diameter. We validated a pharmacological method and a physical method which allowed us to control cerebral vessel diameter while simultaneously recording from nearby neurons and glia. We secondarily determined the predilection of certain classes of interneurons location relative to the blood vessels. Future research will bell targeted at these interneurons to see if their relative proximity impacts their responsiveness to changes in blood vessel diameter. Via participation in this project five Queens College undergraduates were supported over the summer months to study hemo-neural interactions in the Moore and Brumberg laboratories. The results of their research have been presented by them at local (Queens College, Sigma Xi Science Fair), regional (Northeast Undergraduate Research on Neuroscience, Urban Universities Conference) and national (Society for Neuroscience) meetings. Additionally, undergraduates have worked on this project during the school year. It is expected that the final stages of the analysis will wrap up shortly and lead to the submission of a high quality publication with several undergraduate co-authors. Additionally, an article published in the Journal of Undergraduate Neuroscience Education provided the educational/scientific community with low cost options about how to teach about the cerebral vasculature in undergraduate science classes.
