主催: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
会議名: WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
開催地: Kyoto
開催日: 2018/07/01 - 2018/07/06
Background
Animals decide what kind of behavior they should take based on the balance between positive motivation to promote behavior and negative motivation to prevent behavior. However, neuronal circuit mechanism underlying motivated behaviors in a conflicting context is not fully understood.
Methods
We used a conflict behavioral task in which mice were presented appetitive stimuli (sucrose) and aversive stimuli (electric foot-shocks) in the same context. The context was composed of white smooth floor and grid floor. Under food restriction, mice were exposed to a start area on the smooth floor and given sucrose when they reach to a sucrose plate on the grid floor. Once they learned association between the context and sucrose, electric foot-shocks were given to the mice when they step on the grid floor. Their behavior was monitored by a camera and the latency to reach to the sucrose plate was calculated. Brains were removed 90 minutes after the behavioral task and a neuronal activity marker, c-Fos, was immunostained. For pharmacological inactivation of the medial prefrontal cortex (mPFC), GABAA receptor agonist, muscimol (0.05 µg/side), was locally injected into the mPFC 30 minutes before the behavioral task.
Results
The latency to reach to the sucrose plate became shorter with context-sucrose association. After foot shock presentation, however, mice hesitated to step on the grid floor, and as a result, the latency became longer. c-Fos immunostaining revealed that mPFC, nucleus accumbens, amygdala and periaqueductal gray were activated in the conflicting context. Pharmacological inactivation of mPFC shortened the latency to reach to the sucrose plate. To further investigate the role of mPFC, we monitored neuronal circuit activities from free-behaving mice using fiber photometry. Using a retrograde variant of recombinant adeno-associated virus (rAAV2-retro), calcium indicator GCaMP6 was expressed in the mPFC neurons projecting to the specific target brain regions. GCaMP6 fluorescence was monitored through optic fibers implanted into the brain.
Conclusions
These results show the involvement of mPFC in motivated behavior in a conflicting context. Neural projection dynamics during the motivated behavior will be discussed at the conference.
