NMDA receptors assessed by autoradiography with [3H]L-689,560 are present but not enriched on corticofugal-projecting pyramidal neurones.
Experimental lesions followed by binding of [3H]4-trans-2-carboxy-5,7-dichloro-4-phenylamino-carbonylamino-1,2 ,3,4- tetrahydroquinoline ([3H]L-689,560, a novel ligand that binds to the glycine modulatory site), [3H]glycine and [3H]glutamate (N-methyl-D-aspartate (NMDA) sensitive) to cryostat sections and quantitative autoradiography were used to investigate the cellular localization of the NMDA receptor complex in the neocortex of the rat. The lesions were produced by intrastriatal injections of either volkensin (2 and 6 ng) or ricin (10 ng): both are suicide transport agents but only the former is retrogradely transported in the CNS. The binding of [3H]L-689,560 was significantly reduced in rats receiving 2 or 6 ng volkensin in deep cortical layers of Fr1/Fr2 ipsilateral to the striatal lesion. Similar reductions were also seen in [3H]glycine and [3H]glutamate binding, but only in rats receiving 6 ng volkensin. Quantitative histological analysis had previously revealed a loss of large infragranular pyramidal neurones with sparing of both interneurones and supragranular pyramidal neurones. There were no significant reductions in binding of any ligand in the superficial layers. In cortical areas Par1/Par2, [3H]L-689,560 was also significantly reduced in deep layers but only in rats receiving 6 ng volkensin. Binding was also reduced in the superficial layers by contrast to Fr1/Fr2. [3H]Glycine and [3H]glutamate binding were unaffected in this area. Binding of [3H]L-689,560 was unaffected in any area following intrastriatal ricin injection. The present study indicates that the NMDA receptor complex is present on pyramidal cells forming the corticofugal pathways. This is discussed in terms of the 5-HT1A receptor which is enriched on these cells.
Miriam Marks Department of Neurochemistry, Institute of Neurology, London, UK.
M N
MN
Pangalos
P T
PT
Francis
A C
AC
Foster
R C
RC
Pearson
D N
DN
Middlemiss
D M
DM
Bowen
D000634:Aminoquinolines / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D002540:Cerebral Cortex / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005998:Glycine / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009434:Neural Pathways / Q000378:metabolism; D009476:Neurons, Efferent / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013331:Strychnine / Q000494:pharmacology; D014316:Tritium
D000634:Aminoquinolines; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; C074617:4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline; D018698:Glutamic Acid; D016202:N-Methylaspartate; D013331:Strychnine; D005998:Glycine