AAV-mediated hippocampal expression of short and long Homer 1 proteins differentially affect cognition and seizure activity in adult rats.
Homer proteins mediate molecular rearrangements leading to changes in spine morphology. This points to a role of Homer in learning and memory. Homer 1c features both the ligand binding domain and a coiled-coiled domain for self-multimerization. Homer 1a lacks the coiled-coiled domain. Here, we report a new isoform which we termed 1g, lacking the Homer ligand binding domain. We dissected the functional roles of the individual Homer 1 domains, encoded by Homer 1a, 1c, and 1g, in vivo. Recombinant adeno-associated virus (AAV)-mediated overexpression of these forms in the hippocampus of adult rats has opposing effects on learning behavior. Increased levels of Homer 1a impaired hippocampal-dependent memory, while Homer 1g and 1c slightly enhanced memory performance. Homer 1g induced anxiety. Moreover, AAV-Homer 1a animals showed attenuation of electrographic seizures in a model of status epilepticus. These results suggest that Homer 1 proteins play an active role in behavioral plasticity.
Klugmann
Matthias
M
Department of Molecular Medicine and Pathology, Functional Genomics and Translational Neuroscience Laboratory, University of Auckland, Auckland, New Zealand. m.klugmann@auckland.ac.nz
Symes
C Wymond
CW
Leichtlein
Claudia B
CB
Klaussner
Bettina K
BK
Dunning
Jane
J
Fong
Dahna
D
Young
Deborah
D
During
Matthew J
MJ
D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D003071:Cognition / Q000502:physiology; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D000072233:Homer Scaffolding Proteins; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins