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Dr. Barrionuevo is Professor in the Department of Neuroscience at the University of Pittsburgh. People working in this laboratory study synaptic plasticity and biophysical properties of neurons in the hippocampus and prefrontal cortex.
The hippocampus and prefrontal cortex are two cortical structures that are known to play important roles in the formation and tempory storage of declarative memories. Research in my lab focuses on understanding the the physiological, biophysical and anatomical properties of neurons in these two areas using the in vitro brain slice preparation, as well as in vivo recording from the hippocampus of anaesthetized animals. Our working hypothesis is that knowledge of the cellular and circuit properties of these two cortical structures will allow us to better understand how these brain regions function as parts of the brain's memory systems
Damage to the hippocampal formation in humans and animal subjects results in deficits to form long-term episodic memories. While the mechanisms allowing the hippocampus to support the formation of such memories are still unknown, one key assumption underlying many computational models of the hippocampus is that area CA3 is capable of robust "pattern separation". Pattern separation refers to the ability of the CA3 neuronal network to represent cortical activity while minimizing overlap of cortical representations. Computer simulations indicate that pattern separation can be achieved by coordinated activation of a weak and diffuse input to convey the memory representation from the entorhinal cortex (EC), and a strong but sparse input to select the subpopulations of CA3 pyramidal cells that establish non-overlapping memory representations via their recurrent collaterals. Indeed, one unique feature of hippocampal CA3 pyramidal cells is that they receive two converging excitatory inputs from EC. One input is conveyed monosynaptically via the perforant path (PP), and is relatively weak and diffuse. The second input from EC is conveyed disynaptically via the mossy fiber (MF) axons of dentate gyrus granule cells, and is sparse and strong. An important issue is whether the sparseness and strength of the mossy fiber synaptic input are the only features at play during pattern separation. For example, MF axons innervate more interneurons than pyramidal cells; thus, granule cell discharge exerts a strong inhibitory control over pyramidal cell firing, which could further "sharpen" the focus of the MF excitatory drive onto the CA3 neuronal network.
One long-standing hypothesis in the study of the biological mechanisms of memory storage is that the formation of new memories requires long-lasting synaptic modification. In the hippocampus, long-term potentiation (LTP) and depression (LTD) of synaptic strength has been widely studied as a possible mechanism of memory storage. LTP is a persistent increase in synaptic efficacy that can be induced by brief repetitive (tetanic) stimulation of a glutamatergic input to a neuron. Classical LTP (cLTP) is NMDA receptor-dependent and synapse specific, i.e., confined to the tetanized input. In contrast, mossy fiber LTP (MFLTP) in the CA3 region of the hippocampus is NMDA receptor-independent. Recently we have characterized the induction requirements for Hebbian and non-Hebbian forms of mossy fiber LTP in both the rat and the monkey.
A second area of research in my lab centers around the understanding
of the role played by the perforant path input to pyramidal neurons in
area CA3 of the hippocampus. Specifically, we are trying to determine whether
postsynaptic voltage-dependent conductances are involved in amplifying
the propagation of perforant path synaptic responses to the soma. If perforant
path synaptic input does activate voltage-dependent conductances, then
this will have very interesting implications for how CA3 cells integrate
the converging signals that they receive from the entorhinal cortex.
Recently my lab has begun to study the functional circuitry of the prefrontal cortex and the role that dopamine may play in the function and dysfunction of this functional circuitry.
Fleck, M. W., Henze, D. A., Barrionuevo, G., and Palmer, A. M. (1993). Aspartate and glutamate mediate excitatory synaptic transmission in area CA1 of the hippocampus. Journal of Neuroscience 13: 3944-3955.
Langdon, R. B., Johnson, J. W., and Barrionuevo, G. (1993). Asynchrony of mossy fiber inputs and excitatory postsynaptic currents in rat hippocampus. Journal of Neurophysiology (London) 472: 157-176.
Thiels, E., Barrionuevo, G., and Berger, T. W. (1995). Excitatory stimulation during postsynaptic inhibition induces long-term depression in hippocampus in vivo. Journal of Neurophysiology 72: 3009-3016.
Langdon, R. B., Johnson, J. W., and Barrionuevo, G. (1995). Posttetanic potentiation and presynaptically induced long-term potentiation at the mossy fiber synapse in rat hippocampus. Journal of Neurobiology.
Thiels, E., Xie, X., Yeckel, M.F., Barrionuevo, G., and Berger, T.W. (1996) NMDA receptor- dependent LTD in different fields of the hipppcampus in vivo and in vitro. Hippocampus 6: 43-51.
Henze, D.A., Cameron, W.E., and Barrionuevo, G. (1996) Dendritic morphology and its effects on the amplitude and rise time of synaptic signals in hippocampal CA3 pyramidal cells. Journal of Comparative Neurology 369: 331-344.
Urban, N.N. and Barrionuevo, G. (1996) Induction of Hebbian and non-Hebbian LTP at the hippocampal mossy fiber synapse by distinct patterns of high frequency stimulation. Journal of Neuroscience 16(13): 4293-4299.
Urban, N.N., Henze, D.A., Lewis, D.A., and Barrionuevo, G. (1996) Properties of LTP induction in area CA3 of the primate hippocampus. Learning and Memory 3: 86-95.
Xie, ,X., Barrionuevo, G. and Berger, T.W. (1996) Differential expression of short-term potentiation by AMPA and NMDA receptors in the dentate gyrus. Learning and Memory 3: 115-123.
Henze, D.A., Card, J.P., Barrionuevo, G., and Ben-Ari, Y. (1997) Large amplitude miniature excitatory postsynaptic currents in hippocampal CA3 neurons are of mossy fiber origin. Journal of Neurophysiology 77: 1075-1086.
Henze, D.A., Urban, N.N., and Barrionuevo, G, (1997) Origin of the apparent asynchronous activity of hippocampal mossy fibers. Journal of Neurophysiology 78: 24-30.
Berzhanskaya, J., Urban, N.N., and Barrionuevo, G. (1998) Pharmacological characterization of the Monosynaptic Perforant Path Input to CA3 Pyramidal Neurons. J. Neurophysiol., 79: 2111-2118.
Thiels, E., Norman, E.D., Barrionuevo, G., and Klann, E. (1998) Transient and Persistent Increases in Protein Phosphatase Activity During Long-term Depression in Adult Hippocampus In Vivo. Neuroscience. 86(4):1023-1029.
Urban, N.N., Henze, D.A., Barrionuevo, G. (1998) Amplification of PErforant path EPSPs in CA3 pyramidal cells by LVA Caclium and Sodium Channels. J. Neurophysiology. In Press
Urban, N.N., and Barrionuevo, G. (1998) Active Summation of EPSPs in CA3 Pyramidal Neurons. PNAS. In Press.
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Last updated on 22 March 2004.