Open AccessRegulation of motor performance and striatal function by synaptic scaffolding proteins of the Homer1 family
Author(s) -
Anke Tappe,
Rohini Kuner
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0505900103
Subject(s) - metabotropic glutamate receptor , metabotropic glutamate receptor 1 , neuroscience , biology , medium spiny neuron , metabotropic glutamate receptor 6 , striatum , microbiology and biotechnology , scaffold protein , metabotropic glutamate receptor 5 , glutamate receptor , metabotropic glutamate receptor 7 , receptor , signal transduction , biochemistry , dopamine
Intracellular calcium mobilization and signaling mechanisms triggered by activation of synaptic glutamate receptors in the striatum are important modulators of neurotransmission in striatal circuits. However, the expression and functions of scaffolding proteins anchoring glutamate receptors at striatal synapses have not been addressed so far. The long-form Homer1 proteins, Homer1b/c, assemble group I metabotropic glutamate receptors (mGluR1/5) in large macromolecular complexes with sources of calcium influx and release at synapses as well as with components of the NMDA receptor complex at the neuronal cell membrane. Homer1a, the short, activity-dependent splice variant of Homer1b/c, lacks the ability of linking mGluR1/5 to synaptic proteins and functions as an endogenous negative modulator of the mGluR1/5 inositol 1,4,5-trisphosphate receptor signaling complex. We have generated transgenic mice, which overexpress Homer1a in striatal medium spiny neurons either homogenously throughout the extrastriosomal matrix (Homer1a-matrix line) or predominantly in striosomal patches (Homer1a-striosome line). Homer1a-expressing mice demonstrated normal development of striatal structure and afferent–efferent connectivity. However, motor performance in behavioral tasks and striatal responses to the psychomotor stimulant amphetamine were significantly altered in the Homer1a-striosome line. Thus, glutamate receptor scaffolding proteins of the Homer1 family critically regulate the functions of striatal medium spiny neurons in complex motor tasks and its modulation by psychomotor stimulant drugs.