Differential roles of nonsynaptic and synaptic plasticity in operant reward learning-induced compulsive behavior.
BACKGROUND
Rewarding stimuli in associative learning can transform the irregularly and infrequently generated motor patterns underlying motivated behaviors into output for accelerated and stereotyped repetitive action. This transition to compulsive behavioral expression is associated with modified synaptic and membrane properties of central neurons, but establishing the causal relationships between cellular plasticity and motor adaptation has remained a challenge.


RESULTS
We found previously that changes in the intrinsic excitability and electrical synapses of identified neurons in Aplysia's central pattern-generating network for feeding are correlated with a switch to compulsive-like motor output expression induced by in vivo operant conditioning. Here, we used specific computer-simulated ionic currents in vitro to selectively replicate or suppress the membrane and synaptic plasticity resulting from this learning. In naive in vitro preparations, such experimental manipulation of neuronal membrane properties alone increased the frequency but not the regularity of feeding motor output found in preparations from operantly trained animals. On the other hand, changes in synaptic strength alone switched the regularity but not the frequency of feeding output from naive to trained states. However, simultaneously imposed changes in both membrane and synaptic properties reproduced both major aspects of the motor plasticity. Conversely, in preparations from trained animals, experimental suppression of the membrane and synaptic plasticity abolished the increase in frequency and regularity of the learned motor output expression.


CONCLUSIONS
These data establish direct causality for the contributions of distinct synaptic and nonsynaptic adaptive processes to complementary facets of a compulsive behavior resulting from operant reward learning.
Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), Université de Bordeaux, UMR 5287, 33000 Bordeaux, France; CNRS, INCIA, UMR 5287, 33000 Bordeaux, France; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
Fred
F
Sieling
Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), Université de Bordeaux, UMR 5287, 33000 Bordeaux, France; CNRS, INCIA, UMR 5287, 33000 Bordeaux, France.
Alexis
A
Bédécarrats
Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), Université de Bordeaux, UMR 5287, 33000 Bordeaux, France; CNRS, INCIA, UMR 5287, 33000 Bordeaux, France.
John
J
Simmers
Department of Biology, Emory University, Atlanta, GA 30322, USA.
Astrid A
AA
Prinz
Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), Université de Bordeaux, UMR 5287, 33000 Bordeaux, France; CNRS, INCIA, UMR 5287, 33000 Bordeaux, France. Electronic address: romuald.nargeot@u-bordeaux2.fr.
Romuald
R
Nargeot
D000818:Animals; D001048:Aplysia; D003192:Compulsive Behavior; D003216:Conditioning, Operant; D004558:Electric Stimulation; D004594:Electrophysiology; D005247:Feeding Behavior / Q000502:physiology*; D017952:Ganglia, Invertebrate / Q000502:physiology; D007858:Learning; D008564:Membrane Potentials / Q000502:physiology; D009061:Mouth Mucosa / Q000294:innervation; D009473:Neuronal Plasticity / Q000502:physiology*; D012201:Reward