[Abstract Title]. - Society for Neuroscience

phenotype.
This study confirms our previous finding that molecular pathways coupled to the gating of
NMDA receptors are altered in the Ts65Dn mouse and brings us a step closer to understanding
the role of NMDA receptors in the pathogenesis of the cognitive deficits associated with Down
syndrome.
Disclosures: J.J. Scott-McKean, None; K.E. Smith, None; M.L. Dell'Acqua, None; A.C.S.
Costa, Forest Pharmaceuticals, B. Research Grant (principal investigator, collaborator or
consultant and pending grants as well as grants already received).
Poster
238. LTD: Hippocampus and Cortex
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 238.12/D57
Topic: B.08.f. Long-term depression ( LTD )
Support: partly sponsored by Neurosearch A/S
Title: Identification of a small molecule inhibitor of the PICK1 PDZ domain that attenuates LTD
in CA1 neurons
Authors: *T. S. THORSEN 1 , K. MADSEN 1 , N. REBOLA 2 , A. BACH 3 , T. BEUMING 4 , I.
MOREIRA 4 , N. STUHR-HANSEN 3 , D. PETERS 5 , T. DYHRING 5 , H. WEINSTEIN 4 , K.
STRØMGAARD 3 , C. MULLE 2 , L. RØNN 5 , U. GETHER 1 ;
1 Univ. Copenhagen, Copenhagen N, Denmark; 2 Inst. des Neurosciences de Bordeaux, Univ.
Bordeaux, Bordeaux, France; 3 Dept. of Medicinal Chem., Univ. of Copenhagen, Copenhagen Ø,
Denmark; 4 Dept. of Physiol. and Biophysics,, Weill Med. Col. of Cornell Univ., New York, NY;
5 Neurosearch A/S, Ballerup, Denmark
Abstract: PICK1 (Protein Interacting with C Kinase 1) contains an N-terminal PDZ domain
known to mediate interaction with the C-termini of the GluR2 subunit of the AMPA receptor,
with the dopamine transporter (DAT) as well as with several G protein coupled receptors, ion
channels and kinases including protein kinase Cα. PICK1 is necessary for AMPA receptorrelated
neuroplasticity associated with sensitization processes underlying e.g. neuropathic pain
and cocaine addiction. Specifically, PICK1 is believed to be responsible for intracellular
accumulation of the AMPA receptor, a process necessary for expression of Long Term
Depression (LTD). Inhibitors of the PICK1 PDZ domain may accordingly prove useful for
treatment of diseases involving abnormal synaptic plasticity. To identify such inhibitors, we
screened a library of 44,000 random compounds using a previously described fluorescence