UC San Diego

Neuromodulatory neurons release neurotransmitters extrasynaptically to modulate large groups of neurons. Although much work has been done to understand neuromodulation, this has been primarily measured indirectly via action potentials recorded electrically from neuromodulatory somata. In this work, we use genetically modified CNiFER cells, a technique developed in the Kleinfeld lab, to directly measure changes in neuromodulator concentration in real-time. We focus our investigation primarily on cortical noradrenaline, dopamine and acetylcholine, for which CNiFER cells have already been developed. We ask whether spontaneous neuromodulator release occurs in cortex of mice. We find that, indeed, spontaneous dopamine, noradrenaline, and acetylcholine transients occur in cortex of mice. Furthermore, we use real-time feedback of cortical neuromodulation and reinforcement to show that mice can volitionally increase cortical dopamine and noradrenaline levels. We show that mice are able to volitionally link spontaneous dopamine transients to future reward.