Disclosed are methods and systems and methods for methods for neuromodulation of deep-brain and other neural targets in mammals using optogenetics to treat clinical conditions or achievement of a physiological state. The neuromodulation can produce acute or long-term effects. The latter occur through Long-Term Depression (LTD) and Long-Term Potentiation (LTP) via training. Included is control of optical intensity/amplitude, pulse width, pulse shape, pulse rate, burst frequency, pulse pattern, burst rate, burst width, and optical-fiber configuration including through the stimulation of incorporated opsins in the target neural membranes accomplishing up-regulation and/or down-regulation.