Cortistatin overexpression in transgenic mice produces deficits in synaptic plasticity and learning.
Cortistatin-14 (CST) is a neuropeptide expressed in cortical and hippocampal interneurons that shares 11 of 14 residues with somatostatin. In contrast to somatostatin, infusion of CST decreases locomotor activity and selectively enhances slow wave sleep. Here, we show that transgenic mice that overexpress cortistatin under the control of neuron-specific enolase promoter do not express long-term potentiation in the dentate gyrus. This blockade of dentate LTP correlates with profound impairment of hippocampal-dependent spatial learning. Exogenously applied CST to slices of wild-type mice also blocked induction of LTP in the dentate gyrus. Our findings implicate cortistatin in the modulation of synaptic plasticity and cognitive function. Thus, increases in hippocampal cortistatin expression during aging could have an impact on age-related cognitive deficits.
Tallent
Melanie K
MK
Department of Pharmacology and Physiology, Drexel University, University College of Medicine, Philadelphia, PA 19102, USA.
Fabre
Véronique
V
Qiu
Cuie
C
Calbet
Marta
M
Lamp
Tyra
T
Baratta
Michael V
MV
Suzuki
Chisa
C
Levy
Coree L
CL
Siggins
George R
GR
Henriksen
Steven J
SJ
Criado
José R
JR
Roberts
Amanda
A
de Lecea
Luis
L
D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D007858:Learning / Q000502:physiology*; D007859:Learning Disabilities / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics*
D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C054598:corticostatin