Nicotine control of dopamine signaling in the Ventral Tegmental Area

Michael Graupner (1) , Boris Gutkin (1)

1 Group for Neural Theory [Paris]

Midbrain dopaminergic (DA) neurons signal motivational properties of natural reinforces and addictive drugs. Nicotine, like other drugs of abuse, boosts DA output from the ventral tegmental area (VTA). This increase results from direct stimulation of nicotinic acetylcholine receptors (nAChRs) expressed in the VTA. However, how the DA signal is constructed in the VTA and how nicotine changes this signal remains controversial. In particular, {\it in vivo} and {\it in vitro} experimental paradigms reach contradictory conclusions about the key target of nicotine action: direct DA cell stimulation or indirect effects mediated through the GABAergic inter-neurons. We address these issues through computational modeling of the VTA circuitry and nAChR function, based on known activation and desensitization properties of the nAChR subtypes. We show that the apparent data mismatch between {\it in vitro} and {\it in vivo} recordings can be reconciled by differences in the afferent input activity. We find that the GABA cells are principle in causing nicotine dependent DA signals. We pin-point the specific contributions of various nAChRs to the DA signal. These results can help understand how the VTA mediates the rewarding properties of nicotine.

Mots clés: Reward systems; decision-making; Neural coding

Domaines: Neurosciences [q-bio.NC]; Neurosciences

Michael Graupner, Boris Gutkin. Nicotine control of dopamine signaling in the Ventral Tegmental Area. Deuxième conférence française de Neurosciences Computationnelles, "Neurocomp08", Oct 2008, Marseille, France. ⟨hal-00331608⟩