The birth of the neuromolecular gaze

In order to determine whether spinothalamic neurons in the lumbar spinal cord of the rat process neurokinin-1 (substance P) receptors, we injected cholera toxin B subunit into the thalamus and carried out dual-labelling immunocytochemistry to search for neurons that were immunoreactive with antibodies to cholera toxin and neurokinin-1 receptor. We examined 356 spinothalamic neurons in transverse sections and found that 35% of these were neurokinin-1 receptor-immunoreactive. Double-labelled cells made up the majority of the spinothalamic population in lamina I and the lateral spinal nucleus, and were also present in laminae III-V and the area around the central canal. On the side contralateral to the injection site, 77% of spinothalamic neurons in lamina I also showed neurokinin-1 receptor immunoreactivity, while 33% of those in laminae III-V and 14% of the ventromedial group possessed the receptor. Several of the double-labelled neurons with cell bodies in laminae III and IV had dendrites which could be followed dorsally into the superficial dorsal horn. These results indicate that substance P released from nociceptive primary afferents into the superficial dorsal horn is likely to act on spinothalamic tract neurons in lamina I, and also on those with cells bodies in laminae III-IV and long dorsal dendrites.

One of the most significant developments in biology in the past half century was the emergence, in the late 1950s and early 1960s, of neuroscience as a distinct discipline. We review here factors that led to the convergence into a common discipline of the traditional fields of neurophysiology, neuroanatomy, neurochemistry, and behavior, and we emphasize the seminal roles played by David McKenzie Rioch, Francis O Schmitt, and especially Stephen W Kuffler in creating neuroscience as we now know it. The application of the techniques of molecular and cellular biology to the study of the nervous system has greatly accelerated our understanding of the mechanisms involved in neuronal signaling, neural development, and the function of the major sensory and motor systems of the brain. The elucidation of the underlying causes of most neurological and psychiatric disorders has proved to be more difficult; but striking progress is now being made in determining the genetic basis of such disorders as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and a number of ion channel and mitochondrial disorders, and a significant start has been made in identifying genetic factors in the etiology of such disorders as manic depressive illness and schizophrenia. These developments presage the emergence in the coming decades of a new nosology, certainly in neurology and perhaps also in psychiatry, based not on symptomatology but on the dysfunction of specific genes, molecules, neuronal organelles and particular neural systems.