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The Journal of Neuroscience, 2001, 21:RC186:1-6
RAPID COMMUNICATION
Leptin Enhances NMDA Receptor Function and Modulates Hippocampal
Synaptic Plasticity
Lynne J.
Shanley1, 2,
Andrew J.
Irving1, 2, and
Jenni
Harvey1, 2
1 Department of Pharmacology and Neuroscience,
Ninewells Hospital and Medical School, University of Dundee, Dundee DD1
9SY, United Kingdom, and 2 Department of Biomedical
Sciences, Institute of Medical Sciences, University of Aberdeen,
Foresterhill, Aberdeen AB25 2ZD, United Kingdom
The obese gene product leptin is an important signaling protein
that regulates food intake and body weight via activation of the
hypothalamic leptin receptor (Ob-Rb; Jacob et al., 1997). However,
there is growing evidence that Ob-Rb is also expressed in CNS regions,
not directly associated with energy homeostasis (Mercer et al., 1996;
Hakansson et al., 1998). In the hippocampus, an area of the brain
involved in learning and memory, we have found that leptin facilitates
the induction of synaptic plasticity. Leptin converts short-term
potentiation of synaptic transmission induced by primed
burst stimulation of the Schaffer collateral commissural pathway into
long-term potentiation. The mechanism underlying this effect
involves facilitation of NMDA receptor function because leptin
rapidly enhances NMDA-induced increases in intracellular
Ca2+ levels
([Ca2+]i) and facilitates NMDA,
but not AMPA, receptor-mediated synaptic transmission. The
signaling mechanism underlying these effects involves activation of
phosphoinositide 3-kinase, mitogen-activated protein kinase, and Src
tyrosine kinases. These data indicate that a novel action of leptin in
the CNS is to facilitate hippocampal synaptic plasticity via enhanced
NMDA receptor-mediated Ca2+ influx. Impairment of
this process may contribute to the cognitive deficits associated with
diabetes mellitus.
Key words:
leptin; NMDA; Ca2+ imaging; PI
3-kinase; MAPK; Src tyrosine kinase
Copyright © Society for Neuroscience 0270-6474//$05.00/0
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