PT  - JOURNAL ARTICLE
AU  - Stephen C. Thornquist
AU  - Maximilian J. Pitsch
AU  - Charlotte S. Auth
AU  - Michael A. Crickmore
TI  - Biochemical computation underlying behavioral decision-making
AID  - 10.1101/2020.03.14.992057
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.14.992057
4099  - http://biorxiv.org/content/early/2020/03/15/2020.03.14.992057.short
4100  - http://biorxiv.org/content/early/2020/03/15/2020.03.14.992057.full
AB  - Computations in the brain are broadly assumed to emerge from patterns of fast electrical activity. Challenging this view, we show that a male fly’s decision to persist in mating, even through a potentially lethal threat, hinges on biochemical computations that enable processing over minutes to hours. Each neuron in a recurrent network measuring time into mating contains slightly different internal molecular estimates of elapsed time. Protein Kinase A (PKA) activity contrasts this internal measurement with input from the other neurons to represent evidence that the network’s goal has been achieved. When consensus is reached, PKA pushes the network toward a large-scale and synchronized burst of calcium influx, which we call an eruption. The eruption functions like an action potential at the level of the network, transforming deliberation within the network into an all-or-nothing output, after which the male will no longer sacrifice his life to continue mating. We detail the continuous transformation between interwoven molecular and electrical information over long timescales in this system, showing how biochemical activity, invisible to most large scale recording techniques, is the key computational currency directing a life-or-death decision.