David Rossi, Ph.D.
firstname.lastname@example.org; Phone: 503-418-2685; Lab Phone: 503-418-2687; Fax: 503-418-2501; Office: NSI building on West Campus; Mail Code: NSI
Synaptic physiology, glutamate, gaba, transporter, brain, ischemia, calcium, plasticity, stroke, neurodegeneration, epsc, epilepsy, excitotoxicity, cerebellum, hippocampus, patch-clamp, imaging, fluorescence, dendrite, development, perinatal, asphyxia, receptor, transmitter, alcohol, nicotine
Preceptor Rotation Availability
Dr. Rossi might be available for preceptor rotations. Please contact him directly to inquire.
Dr. Rossi might be available for mentorship. Please contact him directly to inquire.
Summary of Current Research
1) Abnormal cell signaling in stroke
The first interest is in the mechanisms of brain damage caused by loss of the blood or oxygen supply to the brain, as occurs in cardiac arrest, stroke, head trauma or perinatal asphyxia. The brain is particularly sensitive to an interruption of its blood supply (ischemia) and even brief episodes of ischemia can cause serious brain damage. Glutamate (the main excitatory transmitter in the brain) is a primary trigger of cell death during brain ischemia. Glutamate induced cell death (excitotoxicity) results from the ionic fluxes generated by glutamate receptors, particularly the calcium influx through NMDA receptor channels. GABA, the main inhibitory transmitter in the brain, may also play an important role during ischemia, but its role is less well characterized. We use electrophysiology, pharmacology and fluorescence imaging in brain slices and dissociated cells to try to understand what goes wrong during the early stages of brain ischemia. Specifically, we study how the handling of glutamate and GABA is altered during simulated brain ischemia: what happens to enzymatic processing of these transmitters inside cells, what happens to their transporters, what happens to vesicular release, and what ionic currents do they generate in neurons? How do cells respond to ischemia-evoked changes in glutamate or GABA release and how does this influence cell death? Are these processes the same in neurons and glia, and what kind of intervention during or after an ischemic episode can prevent cell death and brain damage? A major result of this work has been the demonstration that the main cause of glutamate release at the start of a stroke is the reversal of the normal direction of operation of glutamate transporters (See references below).
2) Cell signaling underlying normal information processing in the brain
The second interest is in understanding how cells normally communicate with each other in both the developing and mature brain. We are interested in how a single neurotransmitter, such as glutamate or GABA, can mediate fast signaling with properties dependent on cell type and brain region, but can also influence such diverse processes as cell migration, neurite growth and retraction, and synapse formation and elimination. How do different transmitter receptor subtypes, the subcellular distribution of receptors, different mechanisms of transmitter release and differences in subcellular structure interact to influence signal processing and generate the vast diversity of functions described above. Major results of this work have been the discoveries that, firstly, inhibition of granule cells in the cerebellum is mediated almost entirely by high affinity extrasynaptic receptors, which are activated tonically by the resting GABA concentration in the extracellular space, and are also activated by transmitter spillover from synapses releasing GABA, and, secondly, that during cerebellar development, tonic activation of granule cell NMDA receptors causes a calcium influx that helps the cells migrate to their final position (See references below).
3) Drug and environmental toxin influence on brain signaling and development
As a bridge between the two other topics, we are interested in how environmental toxins and recreational drugs, such as nicotine and alcohol, affect brain development, normal brain signaling, and may interact with malfunction and damage during brain ischemia. Numerous toxins and recreational drugs act on the glutamatergic or GABAergic system, but the specific molecular mechanisms of their actions, and the consequences of their activity are not well understood. We use the methodology described above to determine the specific molecular targets of various environmental compounds, and we are investigating how their activity affects brain signaling acutely or after chronic exposure.
Techniques and collaborations
The main approaches used in my laboratory are electrophysiology, pharmacology and fluorescence imaging applied to brain slices and dissociated cells. Through collaborations with other laboratories we can also employ in vivo brain recording and molecular biological approaches.
Brady J.D., Mohr C. and Rossi D.J. (2010) Vesicular GABA release delays the onset of the Purkinje cell terminal depolarization without affecting tissue swelling in cerebellar slices during simulated ischemia. Neurosci. In Press.
Siegward-M. Elsas, David J. Rossi, Jacob Raber, Garrett White, Carole-Anne Seeley, William L. Gregory, Claudia Mohr, Timothy Pfankuch, and Amala Soumyanath. (2010) Passiflora incarnata L. (Passionflower) extracts elicit GABA currents in hippocampal neurons in vitro, and show anxiogenic and anticonvulsant effects in vivo, varying with extraction method. Phytomedecine. In Press.
Andrade, A.L. and Rossi D.J. (2010) Simulated ischemia induces Ca2+-independent glutamatergic vesicle release through actin filament depolymerization in area CA1 of the hippocampus. J. Physiol. In press.
Mohr C., Brady J.D. and Rossi D.J. (2010) Young age and low temperature, but not female gender delay ATP loss and glutamate release, and protect Purkinje cells during simulated ischemia in cerebellar slices. Neuropharmacol. 58:392-403.
Furness D.N., Dehnes Y., Akhtar A.Q., Rossi D.J., Hamann M., Grutle N.J., Gundersen V., Ullensvang K., Holmseth S., Lehre K.P., Wojewodzic M., Attwell D., Danbolt N.C. (2008) A quantitative assessment of glutamate uptake into hippocampal synaptic terminals and astrocytes: new insights into a neuronal role for EAAT2. Neurosci. 157:80-94.
Rossi, D.J., Brady, J.D., Mohr, C., (2007) Astrocyte metabolism and signaling during brain ischemia. Nature Neurosci. 10:1377-1386.
Hamann, M., Rossi, D.J., Mohr, C., Andrade, A.L., Attwell, D. (2005) The electrical response of cerebellar Purkinje neurons to simulated ischaemia. Brain 128:2408-2420.
Cavelier, P., Hamann, M., Rossi, D., Mobbs, P., Attwell, D., (2005) Tonic excitation and inhibition of neurona: ambient transmitter sources and computational consequences. Prog. Biophys. Mol. Biol. 87:3-16.
Allen, N.J., Rossi, D.J., and Attwell, D. (2004) Sequential release of GABA by exocytosis and reversed uptake leads to neuronal swelling in simulated ischaemia of hippocampal slices. J. Neurosci. 24:3837-3849.
Rossi, D.J., Hamann, M., and Attwell, D. (2003) Multiple modes of GABAergic inhibition of rat cerebellar granule cells. J. Physiol. 548.1:97-110.
Hamann M., Rossi, D.J., and Attwell, D. (2002) Knocking out the glial glutamate transporter GLT-1 reduces glutamate uptake but does not affect hippocampal glutamate dynamics in early simulated ischaemia. Eur. J. Nuerosci. 15:1-8.
Hamann M., Rossi, D.J., and Attwell, D. (2002) Tonic and spillover inhibition of granule cells control information flow through cerbellar cortex. Neuron 33:1-20.
Rossi, D.J., Oshima, T., and Attwell, D. (2000) Reversed uptake is the major mechanism of glutamate release in severe brain ischaemia. Nature 403:316-321.
Rossi, D.J. and Hamann, H (1998) Spillover-mediated transmission at inhibitory synapses promoted by high affinity α6 subunit GABAA receptors and glomerular geometry. Neuron 20:783-795.
Also see Dr. Rossi's PubMed Listing
Ph.D., 1995, Northwestern University
Assistant Scientist, Neurological Sciences Institute, OHSU
Yoga, photography, gardening, hiking & camping, skiing, music