Edward J. Green - US grants

Dr. Edward Green is studying the intricate electrophysiology of a brain structure, the hippocampus, which is known to be involved in learning and memory. His work should provide important information regarding the nature of the information processing which takes place in the dentate gyrus, a special region of the hippocampus, during exploratory behavior. Furthermore, this work is designed to evaluate functional alterations in the hippocampus associated with behavioral exploration. The proposed studies will utilize electrophysiological recordings of field potentials and single unit responses of granule cells in the dentate gyrus of freely moving rats. The specific goals of the work include: a) an evaluation of the interaction between the transient alterations in synaptic transmission related to behavioral state, and moderately persistent changes in synaptic efficacy that are associated with exploratory behavior; b) an assessment of the role of adrenal hormones in naturally occurring, synaptic efficacy changes in the dentate gyrus that accompany exploratory behavior; c) a determination of whether the locus coeruleus is necessary for producing environmentally-modulated alterations in granule cell excitability; d) an evaluation of whether naturally- occurring alterations in synaptic efficacy and electrically - induced long-term potentiation share a common synaptic mechanism; and e) a comparison of granule cell unit activity during specific behaviors in the home environment to unit activity during the same behaviors following exploration. Findings from these studies will provide us with detailed information about how a specific area of the brain processes information and retains that information for the purpose of memory storage.

We propose to investigate the mechanisms underlying brain dysfunction following traumatic brain injury (TBI) and to clarify recovery processes that may be targeted for therapeutic intervention. In Part 1 of this project, we propose to combine in vitro neurophysiological techniques with cognitive neurobehavioral assessment to evaluate the temporal course of alterations in hippocampal inhibitory circuitry after trauma and to document evidence for aberrant spatial and movement selective hippocampal cellular discharge. The strength of the relationship between cognitive behavior and these indices of hippocampal circuit dysfunction will clarify the role of the hippocampus in generating the functional deficits associated with TBI and whether hippocampal reorganization contributes to functional recovery. In Part 2, we will investigate the effects of TBI on hippocampal long-term potentiation (LTP) and long-term depression (LTD), using the hippocampal slice preparation. Experiments are proposed that will determine whether TBI-induced over activation of NMDA receptors in hippocampus mediates the suppression of LTP and whether NMDA receptor overactivation in vitro will mimic TBI-induced LTP suppression. In Part 3, we will use a newly developed three-dimensional autoradiographic imaging averaging method of expressing local glucose utilization combined with somatosensory circuit activation to quantitatively pinpoint areas of circuit reorganization after TBI. These functional data will be complemented by immunocytochemical and in situ hybridization studies to assess local alterations in pre- and postsynaptic markers and gene expression associated with circuit remodeling. Finally, slowly developing thalamic retrograde degeneration will be targeted for treatment using basic fibroblast growth factor in an attempt to protect somatosensory circuit structure and function. Together, these studies should contribute new information concerning the response of the nervous system to TBI as well as clarifying recovery mechanisms that may be targeted for therapeutic intervention.

behavior test; brain injury; biomedical facility; psychomotor function; neurophysiology; disease /disorder model; behavioral /social science research tag; laboratory rat;

The purpose of the behavioral core is to evaluate the functional status of neural circuitry following traumatic brain injury in rats and mice, by quantitatively assessing sensorimotor and cognitive behavioral endpoints. Paradigms are designed to assess neurobehavioral deficits associated with fluid percussive TBI in rats, and controlled cortical impact in mice, and to evaluate, when possible, the relation between neurobehavioral endpoints and neuropathological, neurophysiological, and molecular markers. The tests of sensorimotor integration and cognition used in the core have been demonstrated to be sensitive to insults produced by these TBI models, which, at moderate to severe levels of injury severity, produce overt pathology in the pariototemporal cortex, hippocampus and thalamus, and white matter.

The purpose of the behavioral Core is to evaluate the functional status of neural circuitry following traumatic brain injury in rats and mice, by quantitatively assessing sensorimotor and cognitive behavioral endpoints including seizures. Paradigms are designed to assess neurobehavioral deficits associated with fluid percussive TBI in rats, and controlled cortical impact in mice, and to evaluate, when possible, the relation between neurobehavioral endpoints and neuropathological, and neurophysiological markers. The tests of sensorimotor integration and cognition used in the core are have been demonstrated to be sensitive to insults produced by these TBI models, which, at moderate to severe levels of injury severity, produce overt pathology in the parietotemporal cortex, hippocampus, thalamus, and white matter.