This project combines two fundamentally new approaches toward a model for changing the characteristic behavior of drug abuse. It exploits the decision-making neural circuitry of foraging behavior, which is subverted in addictive behavior. The experimental targets are specific neural elements that switch expression of approach and avoidance behaviors. The first approach, by locating and describing neural switches for appetence vs. avoidance in a simple system, provides descriptors to facilitate discovery of similar elements in mammalian brain. The second tests utility of focal switch control for regulating behavioral expression that could markedly alter addiction treatment strategies. Applied to human drug abusers, such methods could lessen the influence of hedonic impulse and enhance effectiveness of conventional treatment. We will utilize the predatory gastropod Pleurobranchaea californica, a simple model system for which neural circuitry of decision is well studied by microelectrode and computational simulation. Our initial specific aim is to characterize the switch neurons that toggle the motor network for directional turning between orienting and avoidance, under the control of appetitive state. We will elucidate effects of altering appetitive state on the switch neurons and consequent motor output of the turns stimulated by appetent and noxious stimuli. Our second specific aim is to achieve an exemplar paradigm in which appetitive stimuli induce involuntary avoidance behavior. We will elucidate biasing of the switch via external intervention. Regulation of the switch will be probed by direct electrical control at the elements themselves via intracellular current injection, by directly modifying the state of the feeding network, and by focal application of neuromodulators to the switch elements. Towards developing and testing a model of neural intervention in drug abuse, we will assess effects of gel beads impregnated with neuromodulators to focally affect switch neuron activity and promote bias in behavioral choice. This project seeks to develop a model for treating addictive behavior through characterizing and regulating neural elements that switch behavior between approach and avoidance. ? ? ?
| Brown, Jeffrey W; Caetano-Anollés, Derek; Catanho, Marianne et al. (2018) Implementing Goal-Directed Foraging Decisions of a Simpler Nervous System in Simulation. eNeuro 5: |
| Gillette, Rhanor; Brown, Jeffrey W (2015) The Sea Slug, Pleurobranchaea californica: A Signpost Species in the Evolution of Complex Nervous Systems and Behavior. Integr Comp Biol 55:1058-69 |
| Hirayama, Keiko; Moroz, Leonid L; Hatcher, Nathan G et al. (2014) Neuromodulatory control of a goal-directed decision. PLoS One 9:e102240 |
| Hirayama, Keiko; Gillette, Rhanor (2012) A neuronal network switch for approach/avoidance toggled by appetitive state. Curr Biol 22:118-23 |
| Yafremava, Liudmila S; Gillette, Rhanor (2011) Putative lateral inhibition in sensory processing for directional turns. J Neurophysiol 105:2885-90 |
