The central hypothesis of the proposal is that interneurons localized in the stratum lacunosum moleculare (SLM Is) in hippocampal area CAS are capable of expressing mossy fiber long-term potentiation (MF LTP). The central hypothesis will be tested with whole-cell recordings from SLM Is, anatomical labeling, and electrical stimulation of MF and PP pathways. These investigations will address the following two Specific Aims.
Aim 1 : To identify the requirements for the induction and maintenance of LTP at MF to SLM I synapses in area CAS of the hippocampus. More specifically, we will test the following hypotheses: a) LTP at MF to SLM I synapses is mediated by postsynaptic Ca2+ via activation of group I mGluR receptors; b) LTP at MF to SLM I synapses is mediated by PKA and PKC activation; and c) The early maintenance phase of LTP at MF to SLM I synapses depends on protein synthesis.
Aim 2 : To examine the changes in efficacy of synaptic integration in SLM I produced by LTP induction at MF to SLM I synapses in area CAS of the hippocampus. More specifically, we will test the following hypotheses: a) MF to SLM I synapses is associated with an increase in supralinear summation between MF and PP synaptic inputs to SLM I; b) The increase in supralinear summation between MF and PP synaptic inputs to SLM I after LTP at MF to SLM I synapses is due to an increase in Ca 2+ currents mediated by the T/R channel subtype; and c) The increase in supralinear summation between MF and PP synaptic inputs to SLM I after LTP at MF to SLM I synapses is blocked by inhibition of protein kinases in the postsynaptic cell.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS024288-16A1
Application #
6868042
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Talley, Edmund M
Project Start
1986-04-01
Project End
2008-06-30
Budget Start
2004-09-20
Budget End
2005-06-30
Support Year
16
Fiscal Year
2004
Total Cost
$259,527
Indirect Cost
Name
University of Pittsburgh
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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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
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
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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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