Professor, Neuroscience University of Pittsburgh Phone: (412) 624-7330 Fax: (412) 624-9198 Email: german@bns.pitt.edu Individual Website: http://www.pitt.edu/~german/

M.D., University of Buenos Aires

Research Interests

Dr. Barrionuevo's laboratory investigates the properties of electrophysiological, biophysical, and use-dependent plasticity of glutamatergic synaptic transmission in two cortical regions: (1) the hippocampus, and (2) the prefrontal cortex. One focus of the research in the hippocampus is on the perforant path (PP) input to area CA3 in the in vitro preparation. The PP input provides a critical input to the hippocampal formation because it carries the information directly from the entorhinal cortex. Because propagation of PP synaptic responses is influenced strongly by the activation of voltage dependent channels (VDCs), we have begun to investigate the effect that modulation of VDCs in CA3 pyramidal cells may have on the properties of PP EPSPs and on synaptic integration. We hypothesize that VDCs are subject to both transient and long lasting modulation by changes in membrane voltage, by neuromodulators such as acetylcholine, and norepinepherine, as well as by elevation of intracellular calcium. Another focus of research in the hippocampus is on CA1 area in the intact anesthetized preparation. In collaboration with Drs. Edda Thiels and Eric Klann, we are investigating the biochemical mechanisms underlying the phenomenon of long-term depression (LTD) of synaptic strength at the Schaffer collateral to CA1 synapse, which is thougth to be involved in memory and learning. We hypothesize that one important biochemical event that contributes to the maintenance of LTD is decreased phosphorylation caused by a decrease in protein kinase activity and/or an increase protein phosphatase activity.

The line of research concerning the prefrontal (PrF) cortex seeks to determine the fundamental principles of synaptic transmission between neurons, in order to provide a basis for future understanding of neocortical pathology in schizophrenia. In collaboration with Dr. David Lewis, we are investigating two particular types of layer 3 pyramidal neuron axon collateral connectivity: 1) short range (shorter than 250 microns); and 2) long range (longer than 500 microns), which forms clusters of terminal fields regularly separated by gaps. In the tangential plane, this arrangement forms a pattern of a stripe_like connectivity or lattice. In addition, we are interested in exploring how glutamatergic synaptic transmission in this area is affected by dopamine, a neuromodulatory system that is thought to be compromised in schizophrenia. These studies provide data whose functional significance will be considered in computational modeling work.

Recent Publications

• González-Burgos G,Krimer LS, Urban NN, Barrionuevo G, Lewis D: Efficacy of sustained excitatory synaptic inputs in primate dorsolateral prefrontal Cortex. Cereb Cortex 14: 530-542, 2004.
• Calixto E, Thiels E, Klann E, Barrionuevo G: Early maintenance of hippocampal mossy fiber LTP depends on protein and RNA synthesis and presynapticgranule cell Integrity. J Neurosci 23: 4842-4849, 2003.
• González-Burgos G, Kröner S, Krimer LS, Seamans K, Urban, NN, Henze DA, Lewis DA, Barrionuevo G: Dopamine modulation of neuronal function in prefrontal cortex. Phys Behav 77: 537-543, 2002.
• Henze DA, McMahon D, Harris KM, Barrionuevo, G. Giant miniature EPSCs at the hippocampal mossy fiber to CA3 pyramidal cell synapse are monoquantal. J Neurophysiol 87: 15-29, 2002.
• McMahon D, Barrionuevo G: . Short and long-term plasticity of the perforant path synapse in hippocampal area CA3. J Neurophysiol 88: 528-533, 2002.
• Urban NN, Gonzalez-Burgos G, Henze DA, Lewis DA, Barrionuevo G: Selective reduction by dopamine of excitatory synaptic inputs to pyramidal neurons in primate prefrontal cortex. J Physiol (Lond)539.3: 707-712, 2002.