Localisation of muscarinic (m1) and other neurotransmitter receptors on corticofugal-projecting pyramidal neurones.

Experimental lesions and quantitative autoradiography were used to investigate the cellular localisation of receptors. Lesions were produced by intrastriatal injections of either volkensin or ricin, only the former is retrogradely transported. Volkensin treatment caused significant losses in Fr1/Fr2 of neocortex in the number of infragranular pyramidal neurones and binding to deep cortical layers of both [3H]pirenzepine (muscarinic cholinergic m1 receptors) and [3H]kainate (kainate sensitive glutamate receptors). In common with previous findings, which also showed sparing of interneurones, supragranular pyramidal neurones were not reduced in number and the binding to deep cortical layers of [3H]8-hydroxy-2-(n-dipropylamino)tetralin (serotonin 1A receptors) was reduced. Significant increases in [3H]prazosin binding to both total alpha adrenoceptors and the alpha 1b subtype were observed in superficial layers. Adrenoceptors were not decreased in any layer. The binding of [3H] GABA to GABAA receptors was not affected at all. Muscarinic receptors and pyramidal neurones were also reduced in deep cortical layers of Par1/Par2 in common with serotonin 1A (5-HT1A) receptors and total alpha receptors were significantly decreased in the middle layers. Overall m1 and kainate receptors were less affected than 5-HT1A receptors. The results are discussed in terms of the biology of cortical pyramidal neurones, drugs for Alzheimer's disease and novel ligands for improving human brain in vivo scanning techniques.