0000000000700865
AUTHOR
Karen K. Szumlinski
Targeting Homer genes using adeno-associated viral vector: lessons learned from behavioural and neurochemical studies.
Over a decade of in-vitro data support a critical role for members of the Homer family of postsynaptic scaffolding proteins in regulating the functional architecture of glutamate synapses. Earlier studies of Homer knockout mice indicated a necessary role for Homer gene products in normal mesocorticolimbic glutamate transmission and behaviours associated therewith. The advent of adeno-associated viral vectors carrying cDNA for, or short hairpin RNA against, specific Homer isoforms enabled the site-directed targeting of Homers to neurons in the brain. This approach has allowed our groups to address developmental issues associated with conventional knockout mice, to confirm active roles for di…
Binge drinking upregulates accumbens mGluR5-Homer2-PI3K signaling: functional implications for alcoholism.
The glutamate receptor-associated protein Homer2 regulates alcohol-induced neuroplasticity within the nucleus accumbens (NAC), but the precise intracellular signaling cascades involved are not known. This study examined the role for NAC metabotropic glutamate receptor (mGluR)-Homer2-phosphatidylinositol 3-kinase (PI3K) signaling in regulating excessive alcohol consumption within the context of the scheduled high alcohol consumption (SHAC) model of binge alcohol drinking. Repeated bouts of binge drinking ( approximately 1.5 g/kg per 30 min) elevated NAC Homer2a/b expression and increased PI3K activity in this region. Virus-mediated knockdown of NAC Homer2b expression attenuated alcohol intak…