Eric Klann
Molecular mechanisms of learning and memory
Our research is focused on the molecular mechanisms involved in
long-term changes in neuronal function and understanding how these
mechanisms might be involved in learning and memory. Hippocampal
long-term potentiation (LTP) and long-term depression (LTD) are two
forms of synpatic plasticity that have been proposed to be cellular
substrates for learning and memory formation in mammals. LTP is a
use-dependent, long-lasting increase in synaptic efficacy, whereas LTD
is a use-dependent decrease in synaptic efficacy. Under the
appropriate conditions, these robust forms of plasticity can be
elicited in either hippocampal slices in vitro or the intact
hippocampus in vivo.
One area of emphasis in my laboratory is the investigation of the role
of reactive oxygen species (ROS) such as superoxide as signaling
molecules during the induction and/or expression of LTP. These studies
include experiments designed to determine which ROS are necessary for
LTP, how ROS are produced in the hippocampus, what types of
modifications ROS induce on their target proteins, and which protein
kinases and protein phosphatases are modified by ROS in the
hippocampus. More recently, we have begun electrophysiological,
biochemical, and behavioral studies with various knockout and
transgenic mice to determine how alterations in the regulation of
superoxide metabolism impact hippocampal LTP and hippocampus-dependent
learning and memory. A closely related line of research concerns
investigations of the aberrant role of ROS in aging-related memory
decline and in mouse models of diseases of memory such as
Alzheimer’s disease.

A second, area of emphasis in my laboratory is the
investigation of the signal transduction pathways involved in the
regulation of protein translation initation factors during LTP and
LTD. These studies include experiments designed to identify the
signaling cascades that link NMDA and metabotropic glutamate receptor
activation to alterations in the phosphorylation of eIF2alpha, eIF4E,
Mnk1, and 4E-BP during various forms of LTP and LTD and whether
alterations in the phosphorylation of these factors occurs during
hippocampus-dependent memory. We also have begun studies with various
knockout and transgenic mice to determine how alterations in the
regulation of protein translation initiation factors impact various
forms of LTP and LTD, as well as hippocampus-dependent learning and
memory. A closely related line of research concerns investigations of
the regulation of protein translation signaling pathways in mouse
models of fragile X mental retardation syndrome.
We employ a multidisciplinary experimental approach to gain a
greater understanding of the molecular mechanisms necessary for
maintaining long-lasting changes in synaptic strength and how these
mechanisms are altered in mouse models of diseases associated with
memory loss. Direct enzymatic assays, immunocytochemistry, and Western
blots with phospho-specific antibodies are coupled with
electrophysiological studies to determine the activity and
phosphorylation state of kinases, phosphatases, and numerous
phosphoproteins during LTP and LTD. Similar biochemical approaches
also are conducted in conjunction with hippocampus-dependent memory
tasks to determine whether molecular changes associated with either
LTP or LTD also are associated with memory formation in the mouse, and
whether these changes are altered in genetically-modified mice that
model diseases of memory and mental retardation.
E-mail: eklann [AT] cns [DOT] nyu [DOT] edu
Representative Publications
L. Hou and E. Klann (2004)
Activation of the phosphoinositide 3-kinase - Akt - mammalian target
of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression.
J. Neurosci. 24: 6352-6361.
E. Klann, M.D. Antion, J.L. Banko, and L. Hou (2004)
Synaptic plasticity and translation initiation.
Learn. Mem. 11: 365-372.
J.L. Banko, L. Hou, and E. Klann (2004)
NMDA receptor activation results in PKA- and ERK-dependent Mnk1 activation and
increased eIF4E phosphorylation in hippocampal area CA1.
J. Neurochem. 91: 462-470.
E. Klann, and T.E. Dever (2004)
Biochemical mechanisms for translational regulation in synaptic
plasticity.
Nat. Rev. Neurosci. 5: 931-942.
M.V. Tejada-Simon, F. Serrano, L.E. Villasana, B.I. Kanterewicz, G.Y. Wu,
M.T. Quinn and E. Klann (2005)
Synaptic localization of a functional NADPH oxidase in the mouse hippocampus.
Mol. Cell. Neurosci. 29: 97-106.
K.T. Kishida, M. Pao, S.M. Holland and E. Klann (2005)
NADPH oxidase is required for NMDA receptor-dependent activation of
ERK in hippocampal area CA1.
J. Neurochem. 94:299-306.
J.L. Banko, F. Poulin, L. Hou, C.T. DeMaria, N. Sonenberg and E. Klann (2005)
The translation repressor 4E-BP2 is a critical regulator of
eIF4F complex formation, synaptic plasticity, and
memory in the hippocampus.
J. Neurosci. 25: 9581-9590.
J.L. Banko, L. Hou, F. Poulin, N. Sonenberg and E. Klann (2006)
Regulation of eukaryotic initiation factor 4E by converging signaling
pathways during metabotropic glutamate receptor-
dependent long-term depression.
J. Neurosci. 26: 2167-2173.
D. Hu, F. Serrano, T.D. Oury, and E. Klann (2006)
Aging-dependent alterations in synaptic
plasticity and memory in mice that
overexpress extracellular superoxide dismutase.
J. Neurosci.
26: 3933-3941.
K.T. Kishida, C.A. Hoeffer, D. Hu, M. Pao, S.M. Holland and E. Klann (2006)
Synaptic plasticity
deficits and mild memory impairments in mouse models of chronic granulomatous disease.
Mol. Cell. Biol. 26: 5908-5920.
L. Hou, M.D. Antion, D. Hu, C.M. Spencer, R.E. Paylor and E. Klann (2006)
Dynamic translational and proteasomal regulation of fragile X mental
retardation protein controls
mGluR-dependent long-term depression.
Neuron 51: 441-454.
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