RT Journal Article
SR Electronic
T1 Quantitative autoradiography reveals selective changes in cerebellar GABA receptors of the rat mutant dystonic
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1874
OP 1885
DO 10.1523/JNEUROSCI.10-06-01874.1990
VO 10
IS 6
A1 M Beales
A1 JF Lorden
A1 E Walz
A1 GA Oltmans
YR 1990
UL http://www.jneurosci.org/content/10/6/1874.abstract
AB In the rat mutant dystonic (dt), glutamic acid decarboxylase (GAD) activity in the deep cerebellar nuclei (DCN) is elevated compared to normal littermates. The distribution of this increase within the DCN, and the effect upon GABA receptor density, was assessed in 25-d-old animals. GAD activity was increased 45, 41, and 74% in the medial, interpositus, and lateral divisions of the DCN, respectively. Autoradiographic analysis of GABAA receptor density, using the ligand 3H-muscimol (MUSC), revealed a significant decrease in MUSC binding in the DCN of the mutant. No changes in the binding of the benzodiazepine ligand 3H-flunitrazepam (FLU) were found in the DCN. At 18 other sites, including motor areas in the brain stem, midbrain, and forebrain, no significant changes were found in either MUSC or FLU binding. There also was a failure to find any significant changes in dt animals in the binding of ligands which label the muscarinic cholinergic receptor, dopamine D2 receptor, or serotonin 5-HT2 receptor. The results support earlier findings that GABAergic activity is increased in Purkinje cell terminals of the dt mutant and suggest that in response to this enhanced activity, GABA receptors in the DCN are down-regulated. At other levels of the neuraxis no consistent changes were found in any of the variables studied, suggesting that cerebellar dysfunction may be a primary component of the dystonic syndrome.