Expression of nerve growth factor, p75, and trk in the somatosensory and motor cortices of mature rats: evidence for local trophic support circuits.

Neurotrophins such as nerve growth factor (NGF) are critical for the maintenance of CNS neurons. We determined the expression of NGF and the neurotrophin receptors p75 and trk in the somatosensory and motor cortices of mature rats with immunohistochemical techniques. Sections of mature rat cortex were processed immunohistochemically with primary antibodies directed against NGF, p75, or trk. The distribution of immunoreactive elements was examined, and stereological techniques were used to determine the density and size of immunoreactive cell bodies. Some sections processed for trk immunoreactivity were examined with an electron microscope. From the size and morphology of the labeled cells, it appeared that only neurons in the gray matter were NGF-positive. NGF was detected in one-third of the neurons in layers II-III, V, and VI of both somatosensory cortex and motor cortex; however, fewer than 1 in 12 of the layer IV neurons was NGF-positive. With the notable exception of layer V, few cell bodies (2-10% of the total population) were p75- or trk-immunoreactive. Layer Vb was replete with receptor-positive cell bodies; more than one-third of the layer Vb neurons were p75- or trk-positive. All labeled cells appeared to be pyramidal neurons. The distribution of p75 labeling with the two anti-p75 antibodies was indistinguishable. In addition, the neuropil in the supragranular laminae was p75- or trk-positive. Electron microscopy showed that trk immunoreactivity was also expressed by dendrites. Only rarely were immunoreactive axons detected. In summary, NGF is expressed by cortical neurons throughout cortex, and neurotrophin receptors are widely produced by postsynaptic targets. Thus, NGF appears to participate in an intracortical autoregulatory system. The strong expression of neurotrophin receptors by pyramidal neurons in layer Vb (the origin of brainstem and spinal cord projections) suggests that the neurotrophins are especially critical for the regulation of corticofugal projection systems.