TY - JOUR
T1 - Interference with reelin signaling in the lateral entorhinal cortex impairs spatial memory
AU - Stranahan, Alexis M.
AU - Salas-Vega, Sebastian
AU - Jiam, Nicole T.
AU - Gallagher, Michela
N1 - Funding Information:
Over the course of this project, A.M.S. was funded by a Ford Foundation/National Research Council postdoctoral fellowship and by a National Institutes of Health National Research Service Award fellowship (F32 AG03481801) and work was supported by a program project Grant (P01AG009973-18) to M.G. We are grateful to Dr. Andre Goffinet for the antibody against total DAB1.
PY - 2011/9
Y1 - 2011/9
N2 - Entorhinal neurons receive extensive intracortical projections, and form the primary input to the hippocampus via the perforant pathway. The glutamatergic cells of origin for the perforant pathway are distinguished by their expression of reelin, a glycoprotein involved in learning and synaptic plasticity. The functional significance of reelin signaling within the entorhinal cortex, however, remains unexplored. To determine whether interrupting entorhinal reelin signaling might have consequences for learning and memory, we administered recombinant receptor-associated protein (RAP) into the lateral entorhinal cortex (LEC) of young Long-Evans rats. RAP prevents reelin from binding to its receptors, and we verified the knockdown of reelin signaling by quantifying the phosphorylation state of reelin's intracellular signaling target, disabled-1 (DAB1). Effective knockdown of reelin signaling was associated with impaired performance in the hippocampus-dependent version of the water maze. Moreover, inhibition of reelin signaling induced a localized loss of synaptic marker expression in the LEC. These observations support a role for entorhinal reelin signaling in spatial learning, and suggest that an intact reelin signaling pathway is essential for synaptic integrity in the adult entorhinal cortex.
AB - Entorhinal neurons receive extensive intracortical projections, and form the primary input to the hippocampus via the perforant pathway. The glutamatergic cells of origin for the perforant pathway are distinguished by their expression of reelin, a glycoprotein involved in learning and synaptic plasticity. The functional significance of reelin signaling within the entorhinal cortex, however, remains unexplored. To determine whether interrupting entorhinal reelin signaling might have consequences for learning and memory, we administered recombinant receptor-associated protein (RAP) into the lateral entorhinal cortex (LEC) of young Long-Evans rats. RAP prevents reelin from binding to its receptors, and we verified the knockdown of reelin signaling by quantifying the phosphorylation state of reelin's intracellular signaling target, disabled-1 (DAB1). Effective knockdown of reelin signaling was associated with impaired performance in the hippocampus-dependent version of the water maze. Moreover, inhibition of reelin signaling induced a localized loss of synaptic marker expression in the LEC. These observations support a role for entorhinal reelin signaling in spatial learning, and suggest that an intact reelin signaling pathway is essential for synaptic integrity in the adult entorhinal cortex.
KW - Disabled-1
KW - Learning
KW - Receptor-associated protein
KW - Synaptophysin
UR - http://www.scopus.com/inward/record.url?scp=79960841054&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960841054&partnerID=8YFLogxK
U2 - 10.1016/j.nlm.2011.03.009
DO - 10.1016/j.nlm.2011.03.009
M3 - Article
C2 - 21492744
AN - SCOPUS:79960841054
SN - 1074-7427
VL - 96
SP - 150
EP - 155
JO - Neurobiology of Learning and Memory
JF - Neurobiology of Learning and Memory
IS - 2
ER -