Dopamine actions on the dendritic spines for reward and aversive learning in the nucleus accumbens

[Speaker] Haruo Kasai:1,2
[Co-author] Yusuke Iino:1,2, Ryosuke Nakazato:1,2, Kenji Yamaguchi:1,2, Takeshi Sawada:1,2, Sho Yagishita:1,2
1:Graduate School of Medicine, The University of Tokyo, Laboratory of Structural Physiology, Japan, 2:International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Japan

Behavioral conditioning depends on the firing of dopamine neurons innervating the striatum and cortex, while its synaptic and circuit basis has been elusive. We have reported that optogenetic stimulation of dopamine fibers strengthens spine enlargement induced by STDP in D1 neurons in the nucleus accumbens (NAc), selectively during a short period immediately following the STDP (Yagishita et a. Science 345, 2014). Spines in D1 neurons did not undergo enlargement by STDP even during a baseline firing level of dopamine neurons at 5 Hz unless phasic stimulation (>10 Hz) was applied. We further found that a similar narrow time window in a reward conditioning task when axons from BLA (basolateral amygdala) in NAc was optogenetically stimulated as CS, and followed by US (water). This behavioral result supports that the accumbal spines are responsible for the precisely timed reward learning. In contrast, a short pause of dopamine neuron firing has been proposed to act as a punishment signal, though its synaptic mechanisms have been unclear. We found that a short pause of dopamine neuron firing following STDP was necessary for spine enlargement in D2 neurons when dopamine axons were optogenetically stimulated at 5Hz. Even 0.3 s pause of dopamine neurons was sufficient to trigger spine enlargement in D2 neurons. We found that the enlargement in D2 neurons was induced only in the presence A2A receptor agonist, which stimulates Gs. Indeed, an A2A receptor antagonist blocked punishment learning in the accumbens. Taken together, spine structural plasticity in accumbal medium spine neurons are a very sensitive detector of dopamine firing frequency, and precisely acts as reward prediction error signals, and do so only in the presence of Gs-coupled receptors. Gs-coupled GPCRs in D2 neurons may be a target of psychiatric disorders, such as drug addiction.

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