CNUP Training Faculty

German Barrionuevo, M.D.

Professor, Neuroscience, Center for Neuroscience

M.D. University of Buenos Aires (1971)

Office: 467 Crawford Hall

Synaptic integration and plasticity in hippocampal area CA3.

Research Summary:

Area CA3 is critically involved in the rapid encoding of new contextual memories, spatial working memory, and in spatial pattern separation. Pattern separation refers to the ability of the CA3 neuronal network to represent cortical activity while minimizing overlap of cortical representations. The implementation of rapid encoding and pattern separation is probably related to two unique connectivity features. One unique connectivity feature is that area CA3 receives two external excitatory inputs from the entorhinal cortex (EC). The most important input is conveyed monosynaptically via the perforant path (PP), the axons of stellate cells in EC layer II. The second input from EC is conveyed disynaptically via the mossy fiber (MF) axons of dentate gyrus (DG) granule cells, which in turn receive input from the same layer II cells in EC. Another unique connectivity feature is that CA3 pyramidal cells receive less than one-third of their excitatory drive from other cell populations, and are predominantly connected among themselves via their recurrent collaterals (RC). In addition, the neuronal network in area CA3 is composed of numerous subtypes of inhibitory interneurons which also receive excitatory drive from the EC and RC inputs

Current studies in the laboratory investigate: 1) the isolated AMPAR- and NMDAR-mediated excitatory unitary responses (uAMPA/uNMDA) from RC and PP inputs to CA3 pyramidal cells. The amplitude and kinetic distributions of uAMPA and uNMDA are particularly useful to constrain the corresponding local synaptic parameters in computational models of area CA3. Those local synaptic parameters on the dendrites are not directly measurable due to technical limitations; 2) the types of long term synaptic plasticity (LTP/LTD) that can be expressed at MF and RC inputs to CA3 interneurons; 3) localization of presynaptic calcium channels and metabotropic receptors in MF and RC presynaptic terminals as well as postsynaptic glutamate receptors on CA3 interneurons; and 4) to elucidate the coordination of information transfer from DG and EC to CA3 pyramidal cells. Specifically, this work seeks to understand (a) how biophysical properties of CA3 interneurons controls synaptic integration in pyramidal cells, (b) how these integrative properties are adjusted by activity and neuromodulation, (c) the oscillatory dynamics of these interneurons, and (d) performing statistical analyses to gain information regarding potential classification of interneurons based on functional characteristics.

Selected Publications:

Galván E.J., Pérez-Rosello T., Gómez-Lira G., Lara E., Gutiérrez R. and Barrionuevo, G. Synapse-specific compartmentalization of signaling cascades for LTP induction in CA3 interneurons, Neuroscience, 290: 332-345 (2015).

Perez-Rosello T., Baker, J. L., Ferrante M., Iyengar S. Ascoli G.A., and Barrionuevo, G. Passive and Active Shaping of Unitary Responses from Associational/Commissural and Perforant Path Synapses in Hippocampal CA3 Pyramidal Cells. J. Comput. Neurosci., doi: 10.1007/s10827-010-0303-y

Galván E.J., Cosgrove K.E., and Barrionuevo, G. Multiple Forms of Long-Term Synaptic Plasticity at Hippocampal Mossy Fibers Synapses on Interneurons. Neuropharmacology, doi:10.1016/2010.11.008.

Cosgrove, K.E., Meriney, S.D., and Barrionuevo, G. High Affinity group III mGluRs regulate mossy fiber input to CA3 interneurons. Hippocampus, 2010 (in press).

Galván, E.J., Cosgrove, K.E., Meriney, S.D., Mauna, J.C., Card, J.P., Thiels, E., and Barrionuevo, G. Critical involvement of postsynaptic protein kinase activation in LTP at hippocampal mossy fiber synapses on CA3 interneurons. J. Neuroscience, 30:2844-2855, 2010.

Cosgrove, K.E., Galván, E.J., Meriney, S.D., and Barrionuevo, G. Area CA3 interneurons receive two spatially segregated mossy fiber inputs. Hippocampus, DOI 10.1002/hipo.20713, 2009.

Ascoli, G.A., Brown, K.A., Calixto, E., Card, J.P., Galván, E.J., Perez-Rosello, P., and Barrionuevo, G. Quantitative morphometry of electrophysiologically identified CA3b interneurons reveals robust local geometry and distinct cell classes. J. Comparative. Neurol, 515:677–695, 2009

Galván, E.J, Calixto, E. and Barrionuevo, G. Bidirectional Hebbian Plasticity at Mossy Fiber Synapses on CA3 interneurons. Journal of Neuroscience, 28:14042-14055. 2008.

Calixto, E., Galván E.J., Card, J.P. and Barrionuevo, G. Coincidence Detection of Convergent Perforant Path and Mossy Fibre Inputs by CA3 Interneurons. Journal of Physiology, 586: 2695- 2712, 2008.