[6][7] The theory states that brain computation is organized by a power-of-two-based permutation logic in constructing cell assemblies - the basic building blocks of neural circuits.
In addition, Tsien has also postulated the Neural Self-Information Theory to describe how the brain encodes the moment-to-moment perceptions, memories, spatial navigation, decision-making and conscious action executions.
In 1997, Tsien became a faculty member in the Department of Molecular Biology at Princeton University, where he genetically engineered and created Doogie, a smart mouse.
[2] This transformative technique has led to NIH Blueprint for Neuroscience Research in launching several Cre-driver Mouse Resource projects.
Over the past 20 years, Cre-lox recombination-mediated neurogenetics has emerged as one of the most powerful and versatile technology platforms for cell-specific gene knockouts, transgenic overexpression, neural circuit tracing, Brainbow, optogenetics, CLARITY, voltage imaging and chemical genetics.
[13] While as a faculty at Princeton University, Tsien has speculated that one of the NMDA receptor's subunits may hold the key for superior learning and memory at young ages.
[32][33] However, Dr. Joe Tsien cautions that artificial general intelligence based on the brain's principles can come with great benefits and, potentially, even greater risks.
[34] Moreover, Tsien lab has focused on the cracking of real-time neural code—the rule under which information is signaled to generate the moment-to-moment cognitions including seeing a car, recalling a memory or being consciously aware of time and location.
However, it is obvious the rate code is not how the brain actually uses to represent real-time cognitions due to the enormous firing variabiity from one moment to another.
These surprisals serve as the quanta of information to construct temporally coordinated cell-assembly ternary codes representing real-time cognitions.
[35] Accordingly, Tsien devised a general decoding method and unbiasedly uncovered 15 cell assemblies underlying different sleep cycles, fear-memory experiences, spatial navigation, and 5-choice serial-reaction time (5CSRT) visual-discrimination behaviors.
These results demonstrate that real-time neural codes arise from the temporal assembly of neural-clique members via ISI variability-based self-information principle.