Vernon B. Mountcastle, Jr., was born on July 15, 1918 in Shelbyville, Kentucky into a family of farmers of Scottish descent on both sides. His father was a railroad contractor and his mother a teacher. No member of his family had attained a university education before his own generation. His mother treated him and his siblings as students asking them to repeat their school lessons to her. By the time he was 4 years of age, Mountcastle could read and write.

At 3 years of age Mountcastle moved with his family to Roanoke, Virginia where he attended primary and secondary school. His precocious reading and writing abilities enabled him to skip the first two grades of elementary school education. During childhood he started playing tennis, a sport he continued to play until he was 80 years. In 1935 Mountcastle enrolled in Roanoke College in Salem and in 3 years earned a B.S. in Chemistry with honors. During his college years Mountcastle lived at home and had to commute every single day to a different town. This was in the midst of the Great Depression and Mountcastle always felt lucky he had been able to attend college.

Primarily influenced by one of his chemistry professors, who studied at Johns Hopkins, Mountcastle applied and was accepted at Johns Hopkins Medical School. At that institution, Mountcastle is quoted as saying that he “…had the most fantastic experience. I felt that I was welcomed into a society of scholars. For example we never got any grades. I learned later that there was a very detailed grading of everything. But you were never told. And that produced a fantastic atmosphere. You never felt that you were competing with another student; you were competing with the subject” (Venere 1998).

Mountcastle earned his M.D. from Johns Hopkins in 1942 and interned in Surgery before serving in the U.S. Naval Amphibious Forces for 3 years with two campaigns in the European Theater: Anzio, Italy and Normandy, France. After the war ended, he married Nancy Clayton Pierpont in September, 1945. From his marriage he had three children: Vernon B. Mountcastle III in 1947, Anne Clayton Mountcastle in 1948, and George Earle Pierpont Mountcastle in 1949 (deceased in 1969). He enjoys having six grandchildren and one great grandchild. He considers the time raising his family as the happiest years of his life.

Scientists during the twentieth century assigned body functions to areas of the cortex from observations of region-specific deficits after brain injuries. The legacy of Broca, Wernicke, and Jackson was later on complemented by cytoarchitectural studies that used parameters for cell morphology, density and lamination in order to parcellate the cerebral cortex into an orderly arrangement. Despite the prominent reputation of its proponents the idea of “one” brain region having “one” brain function was never fully accepted and soon faced serious challenges. The British Army neurologist Gordon Holmes (1876–1963) performed experiments on the somatotopic mapping of brain injured patients during World War I that suggested how specific functions could occupy relatively large regions of the cortex. Furthermore, some complex perceptual functions such as spatial localization of an object were not based on a specific area of the brain. This idea received substantial support from the American psychologist and behaviorist Karl Spencer Lashley (1890–1958) whose ablation experiment in rats demonstrated that the amount of cortical tissue removed had a more significant effect on maze learning than the specific locus of a lesion. Lashley’s results lead to the promulgation of the well-known concepts of mass action and equipotentiality. In parallel to these early efforts on brain localization research was spurred by technological needs of World War I.

The signature injury of World War I (1914–1918) was shell shock. The steel helmet was introduced only at the beginning of 1916. Soldiers engaged in static trench warfare without adequate protection were subjected to a barrage of artillery and mortar attacks (Jones et al. 2007). Research into neurotrauma was the harbinger for improved electrical components that would allow mapping of activity within the cortex. Gerard, Marshall, and Saul were the first to apply microelectrodes to the sensory cortex of monkeys to measure the slow-wave potential evoked by the activation of peripheral somatosensory receptors. Sometime in the mid-nineteen-thirties the Physiology Department at the Johns Hopkins School of Medicine developed a program to explore the possibilities afforded by this technique. Under the guidance of Philip Bard (1898–1977), a cadre of dynamic young researchers, including Wade Marshall and Clinton Woolsey, systematically mapped the somatotopic representation of the body of a monkey onto its cortical surface. Although the concept of the homunculus derived from human experiments by Penfield and colleagues gained the attention of the public press the contemporaneous efforts of the Hopkins investigators led to the description of “animalculi” in numerous mammalian species. It thus seemed quite evident that somatotopic representations were an organizing principle for the central nervous system in general and not for the human primate brain alone.

The technique of recording electrical activity from single neurons with an extracellular electrode (single-unit recording) was popularized by Gilbert Ling at the University of Illinois. Ling had done his postdoc at Johns Hopkins Medical School but moved to join Professor Gerard when the latter founded a large research laboratory at the University of Illinois. Soon, studies were been done and published in both invertebrate and vertebrate species as well as in recordings of the brainstem nuclei and thalamus. At the end of World War II Stephen Kuffler (1913–1980) moved from Australia to Hopkins and used the single-unit recording technique to investigate the receptive fields of retinal ganglion cells in the cat. His famous discovery of their center-surround properties stands as one of the classics in neuroscience.

During World War II Mountcastle served 3 years as an officer in the U.S. Naval Medical Corp. After his military duties were over in 1946 he joined the Department of Physiology at the Johns Hopkins School Medicine as a postdoctoral fellow and he never left. He was a contemporary of Stephen Kuffler and to some of his fellows (Hubel and Wiesel). Mountcastle would eventually rise through the academic ranks to become a full professor and hold the position of Director of the Department of Physiology for 17 years (1964–1980).