Evidence for an enhancement of excitatory transmission in adult CNS by Wnt signaling pathway modulation.
The role for Wnt signaling modulation during synaptogenesis, neurogenesis and cell fate specification have been well characterized. In contrast, the roles for Wnt signaling pathways in the regulation of synaptic plasticity and adult physiology are only starting to be elucidated. Here, we have identified a novel series of Wnt pathway small molecule modulators, and report that these and other small molecules targeting the Wnt pathway acutely enhance excitatory transmission in adult hippocampal preparations. Our findings are consistent with a pre- and postsynaptic site of action, leading to both increased spontaneous and evoked neurotransmission that occurs in a transcription-independent fashion.
Beaumont
Vahri
V
The Neuroscience Research Centre, Merck Sharp and Dohme, Terlings Park, Harlow Essex CM20 2QR, UK. vahri@hotmail.com
Thompson
Sally-Anne
SA
Choudhry
Fahd
F
Nuthall
Hugh
H
Glantschnig
Helmut
H
Lipfert
Lorraine
L
David
Gabriela R
GR
Swain
Christopher J
CJ
McAllister
George
G
Munoz-Sanjuan
Ignacio
I
D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D017930:Genes, Reporter; D006146:Guanidines / Q000737:chemistry / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D006146:Guanidines; D051153:Wnt Proteins; C004479:pimagedine