Somatostatin receptor 2 knockout/lacZ knockin mice show impaired motor coordination and reveal sites of somatostatin action within the striatum.
The peptide somatostatin can modulate the functional output of the basal ganglia. The exact sites and mechanisms of this action, however, are poorly understood, and the physiological context in which somatostatin acts is unknown. Somatostatin acts as a neuromodulator via a family of five 7-transmembrane G protein-coupled receptors, SSTR1-5, one of which, SSTR2, is known to be functional in the striatum. We have investigated the role of SSTR2 in basal ganglia function using mice in which Sstr2 has been inactivated and replaced by the lacZ reporter gene. Analysis of Sstr2lacZ expression in the brain by beta-galactosidase histochemistry demonstrated a widespread pattern of expression. By comparison to previously published in situ hybridization and immunohistochemical data, Sstr2lacZ expression was shown to accurately recapitulate that of Sstr2 and thus provided a highly sensitive model to investigate cell-type-specific expression of Sstr2. In the striatum, Sstr2 expression was identified in medium spiny projection neurons restricted to the matrix compartment and in cholinergic interneurons. Sstr2 expression was not detected in any other nuclei of the basal ganglia except for a sparse number of nondopaminergic neurons in the substantia nigra. Microdialysis in the striatum showed Sstr2-null mice were selectively refractory to somatostatin-induced dopamine and glutamate release. In behavioural tests, Sstr2-null mice showed normal levels of locomotor activity and normal coordination in undemanding tasks. However, in beam-walking, a test of fine motor control, Sstr2-null mice were severely impaired. Together these data implicate an important neuromodulatory role for SSTR2 in the striatum.
Allen
Jeremy P
JP
Department of Neurobiology, The Babraham Institute, Babraham, Cambridge, CB2 AT, UK. jem.allen@bbsrc.ac.uk
Hathway
Gareth J
GJ
Clarke
Neil J
NJ
Jowett
Mike I
MI
Topps
Stephanie
S
Kendrick
Keith M
KM
Humphrey
Patrick P A
PP
Wilkinson
Lawrence S
LS
Emson
Piers C
PC
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007763:Lac Operon / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019957:Motor Skills Disorders / Q000235:genetics* / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D013004:Somatostatin / Q000502:physiology*
D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2