171 Ashley Ave.
Charleston, SC 29425
843-792-1414
|
 |
September 2005
Children's Research Institute News Brief
 |
Bernard L. Maria, MD, MBA
Executive Director
Darby Children's Research Inst. |
|
 |
Inderjit Singh, PhD
Scientific Director
Darby Children's Research Inst. |
|
The Children's Research Institute together with the Department of Neurosciences at MUSC is proud to announce the arrival
of their most recent recruit Dr. Prakash Kara, an outstanding developmental and systems neuroscientist from Harvard Medical
School. Dr. Kara has published seminal papers in outstanding journals including Nature, Science, Neuron, Proceedings of the
National Academy of Sciences, and the Journal of Neuroscience. The Children's Research Institute already has considerable
depth and breadth in pediatric neuroscience, including stellar programs in Developmental Neurological Disorders (Dr. Singh);
Pediatric Neuropsychiatry (Drs. Kalivas and Rammamorthy) and Neuro-oncology (Dr. Maria). As an integrative neuroscientist with
expertise in new in vivo function brain imaging and electrophysiological techniques, Dr. Kara complements these disciplines.
By bringing together such a diverse group of neuroscience experts, the Institute aims to comprehensively address pediatric
brain health with every available basic science tool. Our goal is to understand childhood disease of the brain, from the molecular
and cellular mechanisms through to a systems level analysis with cutting edge technology. The unique interdisciplinary structure
of the Children's Research Institute, together with the proven leadership of the Institute Directors and Dept of Neuroscience Chairs,
and the collegiality of the Neuroscience faculty is what convinced Dr. Kara to come to MUSC.
 |
| Dr. Prakash Kara |
Dr. Kara's interest in developmental and systems neuroscience began when he was an honors student at the University of Cape Town, South
Africa. His advisor then, Dr. Rodney Douglas (currently the co-director of the Institute for Neuroinformatics in Zurich,
Switzerland and inventor of the world's first artificial neuron in analog VLSI) suggested Dr. Kara read the developmental
neuroscience work of 1992 Nobel Prize winners Hubel and Wiesel. Monitoring the electrical
activity and mapping the receptive field one neuron at a time in the intact brain, Hubel and Wiesel were the first to demonstrate that
neurons in the visual cortex had exquisite sensitivity to specific features of a visual stimulus (its orientation, direction, velocity,
eye preference). Most importantly, they showed that these neurons in the cerebral cortex were highly susceptible to irreversible loss
of function upon any alteration in sensory experience during postnatal brain development. Hubel and Wiesel's work profoundly influenced
the therapies used when young children incur eye injuries.
Instead of pursuing basic science research that would contribute to further refinements
in purely preventative measures, Dr. Kara chose laboratory research that would eventually help clinicians restore
function in blind patients. After completing his MS thesis at the University of Cape Town, he went to work with pre-eminent
developmental neurobiologist Dr. Mike Friedlander at the University of Alabama at Birmingham. Dr. Friedlander is now the Chair of the
Department of Neuroscience at Baylor College of Medicine.
 |
| In this cartoon illustration of one of Dr. Kara's his experiments, receptive fields of representative neurons are shown in red (on) and blue (off). The retinal and thalamic receptive fields have on centers and off surrounds; the cortical simple cell has vertically oriented on and off subregions. Reliable responses of retinal, thalamic and cortical neurons are shown emerging from each stage. Background: drawing of the primary visual pathway, including projections from the retina (top left) to thalamus (bottom center) to cortex (bottom right). |
Working in Dr. Friedlander's lab, Dr. Kara's PhD thesis work provided the first data to show that nitric oxide, an endogenous gaseous
neurotransmitter, shaped the form and regularity of visual responses in the neonatal and adult cerebral cortex, improving the signal
detection quality by individual neurons. Furthermore, in subjects that experienced long-term sensory deprivation in one eye, nitric
oxide modified the degree of binocular interactions in cortical neurons. Even though Dr. Kara adopted ingenious and sophisticated
techniques to record neural activity and simultaneously manipulate the local microenvironment pharmacologically, the system was analyzed
one neuron at a time, making it difficult to fully understand the underlying contributions from feedforward vs. feedback network connections.
By this time (mid-to-late-90s), Dr. Clay Reid at Harvard Medical School began recording from two areas of the visual system simultaneously
(in adults) to examine the synaptic rules that governed how receptive fields were being transformed from one level to the next in the visual
hierarchy, e.g. thalamus to visual cortex. Dr. Kara joined Dr. Reid's lab in 1998 with the long-term goal of applying some of these
simultaneous recording techniques to examine the developmental mechanisms that drive cortical circuits to acquire their exquisite selectivity
to specific features of the visual stimuli via sensory experience.
Dr. Kara was the first to simultaneously record neural activity from three levels of the visual hierarchy (Neuron, 2000). This work revised
our understanding of the circuit mechanisms that are responsible for maintaining reliable and reproducible neural activation through
successive stages of the brain's visual processing centers, even though the individual synaptic connections in these regions are highly
variable. Although the general wiring of the visual system has been known in outline for some time, in another study, Drs. Kara and Reid
took on the heroic task of testing the effect a single retinal cell had on the firing of an individual neuron in the primary visual cortex,
in vivo. They found that special patterns of retinal activity are required to effectively drive cortical cells to respond to a visual
stimulus. Clinicians who are implanting blind patients with neural-prosthetic devices are paying very close attention to Dr. Kara's research,
as his is the only data available that sheds insight into the patterns of artificial electrical stimulation that would be required to
appropriately activate cortical neurons in blind subjects.
While these multi-electrode electrophysiological techniques proved to be very rewarding for studying feedforward transformations of function
from the periphery (retina) through to the central processing stations in the visual cortex, researchers needed new techniques for the complete
examination of the function of all neurons (thousands) in a local network within the cerebral cortex. Crucial was a high-resolution functional imaging
method, two-photon microscopy and calcium imaging in vivo. Using this new imaging technology in 2005, Dr. Kara was among
collaborators (Ohki, Chung, Ch'ng, and Reid) reporting in Nature a major advance in understanding the microstructure of cortical columns,
showing that the functional architecture of visual cortex is organized with single-neuron or micron-level precision.
 |
| Dr. Kara's lab also takes high-resolution images of the brain in neonates and adults. They look not only at the anatomy -- for example, different cell types (panel A, B)-- but also watch what kinds of sensory (environmental) stimuli these neurons respond to (panels C) - their specific functions in the intact working brain. This imaging technique can show hundreds of neurons light up to specific features of visual stimuli (e.g. at 180, 225 deg in panels C) but remain silent (dark) when all other orientations of visual stimuli are presented. |
The techniques that Dr. Kara helped develop in Dr. Clay Reid's lab at Harvard for studying visual processing in adults now sets the stage for
him to revisit and resolve several problems in mammalian development and plasticity, which he first became interested in over a decade earlier.
The overall goal of Dr. Kara's lab in the Charles P. Darby Children's Research Institute will be to examine how neural connections from the eye to the
brain are refined and remodeled during the critical periods of postnatal development. Dr. Kara will begin his program by examining how signals
from the two eyes are integrated and processed in large networks of cortical neurons, and so study cardinal features of the cortical
architecture, such as the development and plasticity of ocular dominance columns. He will then extend this work to explore the developmental
programs that drive binocular disparity detection (stereo vision). Dr. Kara will collaborate with many of the outstanding neuroscientists in
the Institute and the Department of Neurosciences who work on other aspects of signal processing in the intact brain that mediate addiction,
motivation, and reward.
Dr. Kara will continue to consider the translational applications of how his basic science research can be applied to restoring vision in the
blind. As described above, the pediatric visual system is sensitive to a variety of congenital and acquired diseases or
deprivation of sensory experience through injury. Vision loss in the pediatric population often goes unrecognized, because children are highly
adaptive to visual loss and may not have the same visual demands as adults. The impact of Dr. Kara's research led the head of the Boston Retinal
Implant Project, Dr. Joe Rizzo, to invite Dr. Kara as a collaborator on a NSF grant. This grant proposes to develop new technologies to improve the
design of visual prosthetic devices that will be implanted in the retina of blind human subjects who have lost photoreceptor function. In the
long term, Dr. Kara will work closely with eye specialists in the Children's Hospital and ophthalmology department, with the overarching goal of
making a difference in the lives of children with visual system dysfunction. We are very pleased to welcome Dr. Kara.
Postdoc fellows, residents, students, and technicians who wish to work with Dr. Kara are encouraged to contact him.
|
|
Print Version