Neurotransmitter receptors of rat cortical pyramidal neurones: implications for in vivo imaging and therapy

Pyramidal neurones of the neocortex have been implicated in a number of neuropsychiatric diseases, such as Alzheimer's disease. Markers that may identify these cells have been investigated using a novel technique. A subpopulation of corticifugal neocortical pyramidal neurones was destroyed by the unilateral striatal injection of volkensin, a toxin that undergoes retrograde suicide transport from the site of injection. Striatal volkensin injections produced significant reductions in the number of large pyramidal neurones of the infragranular cortical layer. The selectivity of the lesion was demonstrated by the preservation of cells containing glutamic acid decarboxylase mRNA, which are considered to be cortical interneurones. Ricin, another toxic lectin, but effective as a suicide transport agent exclusively in the PNS, produced local striatal damage but no cortical cell loss. In autoradiographic binding studies of animals treated with volkensin, binding in deep neocortical layers of [3H]8-hydroxy-2-(n-dipropylamino) tetralin ([3H]8-OH-DPAT) to 5-HT1A but not of [3H]ketanserin to 5-HT2 receptors was significantly reduced. The N-methyl-D-aspartate receptor complex was investigated using the novel glycine site antagonist [3H]L-689,560, and the muscarinic M1 receptor using [3H]pirenzepine. Significant reductions in binding of [3H]L-689,560 and [3H]pirenzepine were observed in the deep neocortical layers of the animals that had been injected with volkensin. The rank order of the ligands as effective markers for this subpopulation of pyramidal neurones was [3H]8-OH-DPAT >> [3H]pirenzepine > [3H]L-689,560 >> [3H]ketanserin. These findings are thought to have advanced the understanding of the biology of pyramidal neurones. Implications for in vivo imaging treatment of neuropsychiatric conditions such as Alzheimer's disease are discussed.