Yuste's interest in neuroscience arose early, inspired by books like Santiago Ramón y Cajal's Los Tónicos de la Voluntad: Reglas y consejos sobre investigación científica ) (The Tonics of the Will: Rules and Advice on Scientific Research) and supported by his parents.

[5] He worked for two summers (1985/86) in the laboratory of the Nobel Prize laureate Sydney Brenner at the University of Cambridge, but the budget cuts of Margaret Thatcher's government made him look for PhD opportunities in the United States.

[8] In 2013 Yuste received the NIH Director's Pioneer Award with a grant of US$2.5 million to fund research to test the hypothesis of the cortex as a random circuit using novel two-photon imaging methods in a large-scale study of the mouse cortical microcircuit.

[18][19][4] Yuste has warned against spreading the funds of the initiative too thin and argued that a focused effort is required to develop the technologies needed for large-scale, real-time brain imaging with single-neuron resolution that would be made available at observatory-like centers to the scientific community.

[22] This prize, which is "awarded annually to outstanding leaders who demonstrate the willingness and capacity to address the complexity of 21st-century challenges in innovative, risk-taking, and ethical ways, and whose work is global in aspiration or implication and is rooted in universal values"[23] is a substantial honor.