Neurochemical heterogeneity among corticofugal and callosal projections

Abstract

Biochemical, physiological, and anatomical studies over the past 30 years have firmly established glutamate (Glu) as the major neurotransmitter of those cortical neurons which give rise to corticofugal pathways. In the present study we utilized immunohistochemistry, with an antibody directed against Glu, in conjunction with wheat germ agglutinin-horseradish peroxidase (WGA-HRP) histochemistry to examine the Glu-containing neurons which give rise to corticofugal and callosal projections of the rat. Injections of WGA-HRP into the pons labeled cells in layer V of both visual and somatosensory cortices. WGA-HRP-labeled cells which also stained for Glu were large pyramids and in the visual cortex constituted approximately 42% of the total number of neurons which had effectively transported WGA-HRP, while the percentage was 56% in the somatosensory cortex. Following caudate/putamen injections, WGA-HRP-labeled cells were confined to layer V of the somatosensory and motor cortices. Of these cells, 40% in the somatosensory cortex and 53% in the motor cortex were also stained for Glu. Finally, after WGA-HRP injections in the visual cortex numerous WGA-HRP-positive neurons were found throughout layers II–VI around the boundaries between area 17 and areas 18 and 18a of the contralateral hemisphere. Here, 38% of these cells were also labeled for Glu, but this percentage was higher (49%) when layers II—III were considered alone. These findings show that Glu is not the neurotransmitter used overwhelmingly in corticofugal and callosal projections and that different proportions of neurons are Glu-immunoreactive in the systems examined. This suggests a neurochemical heterogeneity of cortical projection neurons and may explain the reported differential involvement of these neurons in neurodegenerative disorders such as Huntington's disease and Alzheimer's dementia.