Long-term potentiation (LTP) is a persistent enhancement in synaptic efficacy first discovered in the mammalian hippocampus, which can be induced by brief, tetanic stimulation of afferents to its principal neurons (granule cells of the dentate gyrus and pyramidal cells of the CAI and CA3 regions). I have recently demonstrated that the induction of LTP in the CA3 region of the in vitro hippocampal slice preparation results in the efficacy of heterosynaptic (nontetanized) inputs. Specifically, synaptic responses were recorded from CA3 neurons in pharmacologically disinhibited hippocampal slices using current- and voltage-clamp techniuqes. LTP was induced in one of three synaptic inputs converging onto the same CA3 pyramidal cell: the mossy fibers, the Schaffer collateral/co=issural fibers, and the fimbria to characterize changes in efficacy produced in the other two nontetanized inputs. The results indicate that induction of LTP in the mossy fiber input was accompanied by potentiation of Schaffer and fimbria responses, whereas induction of LTP in the Schaffer pathway was associated exclusively with potentiation of fimbria responses. LTP induced in the fimbria was input specific. Neither the intracellular injection of EGTA into CA3 pyramidal cells, or bathapplication of APV blocks the induction of homosynaptic mossy-fiber LTP and the cojoint heterosynaptic LTP expressed in the Schaffer and fimbrial input. In contrast, the induction of homosynaptic LTP in the same fimbrial input is APV sensitive. The present proposal has four interrelated objectives. i) to determine the causal relationship between homo- and heterosynaptic LTP; ii) to investigate some postsynaptic sequelae which could be responsible for the expression of the maintenance of heterosynaptic LTP; iii) to assess whether NE can enable heterosynaptic LTP; and iv) to determine the relationship between heterosynaptic and associative LTP.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024288-06
Application #
3408719
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1986-04-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Arts and Sciences
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Galván, E J; Pérez-Rosello, T; Gómez-Lira, G et al. (2015) Synapse-specific compartmentalization of signaling cascades for LTP induction in CA3 interneurons. Neuroscience 290:332-45
Perez-Rosello, Tamara; Baker, John L; Ferrante, Michele et al. (2011) Passive and active shaping of unitary responses from associational/commissural and perforant path synapses in hippocampal CA3 pyramidal cells. J Comput Neurosci 31:159-82
Cosgrove, Kathleen E; Meriney, Stephen D; Barrionuevo, Germán (2011) High affinity group III mGluRs regulate mossy fiber input to CA3 interneurons. Hippocampus 21:1302-17
Galvan, Emilio J; Cosgrove, Kathleen E; Barrionuevo, German (2011) Multiple forms of long-term synaptic plasticity at hippocampal mossy fiber synapses on interneurons. Neuropharmacology 60:740-7
Anderson, Warren D; Galván, Emilio J; Mauna, Jocelyn C et al. (2011) Properties and functional implications of I (h) in hippocampal area CA3 interneurons. Pflugers Arch 462:895-912
Galvan, Emilio J; Cosgrove, Kathleen E; Mauna, Jocelyn C et al. (2010) Critical involvement of postsynaptic protein kinase activation in long-term potentiation at hippocampal mossy fiber synapses on CA3 interneurons. J Neurosci 30:2844-55
Cosgrove, Kathleen E; Galvan, Emilio J; Meriney, Stephen D et al. (2010) Area CA3 interneurons receive two spatially segregated mossy fiber inputs. Hippocampus 20:1003-9
Ascoli, Giorgio A; Brown, Kerry M; Calixto, Eduardo et al. (2009) Quantitative morphometry of electrophysiologically identified CA3b interneurons reveals robust local geometry and distinct cell classes. J Comp Neurol 515:677-95
Galvan, Emilio J; Calixto, Eduardo; Barrionuevo, German (2008) Bidirectional Hebbian plasticity at hippocampal mossy fiber synapses on CA3 interneurons. J Neurosci 28:14042-55
Scorcioni, Ruggero; Wright, Susan N; Patrick Card, J et al. (2008) Point Analysis in Java applied to histological images of the perforant pathway: a user's account. Neuroinformatics 6:63-7

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