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Mechanisms controlling expression and memory of emotions

開催日 2014/9/11
時間 14:00 - 16:00
会場 Room D(503)
Chairperson(s) 貝淵 弘三 / Kozo Kaibuchi (名古屋大学大学院医学系研究科 / Nagoya University Graduate School of Medicine, Japan)
南 雅文 / Masabumi Minami (北海道大学大学院薬学研究院薬理学研究室 / Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Japan)

A critical time window for dopamine actions on the dendritic spines of nucleus accumbens

  • S1-D-1-4
  • 河西 春郎 / Haruo Kasai:1 柳下 祥 / sho yagishita:1 
  • 1:東京大学 / The University of Tokyo, Japan 

Animal behaviours are only reinforced by rewards that closely follow the behaviours within a narrow time window. The reward is coded by the phasic activity of dopaminergic neurons in the ventral tegmental area (VTA) which densely innervates the medium spiny neurons (MSNs) in the nucleus accumbens of the striatum, a key brain area for reinforcement learning in mammals6. Glutamatergic synapses on dendritic spines of the MSNs also receive sensorimotor inputs that evoke action potentials (APs)7. These concurrent neuronal activities of synaptic inputs and APs can induce spike-timing-dependent plasticity (STDP), a major Hebbian learning mechanism. However, it was unknown whether dopamine reinforces the preceding, but not subsequent, STDP within a specific time window to account for the reward actions. Here, we selectively stimulated dopaminergic and glutamatergic inputs on MSNs by optogenetic stimulation of dopaminergic fibres and two-photon uncaging of caged-glutamates paired with APs (STDP)8,9 in MSNs in acute slices of mouse brain. We found that dopamine markedly potentiated spine enlargement, but this only occurred within a narrow time window (0.3-2 s) closely following STDP, which is consistent with behavioural conditioning findings. Imaging of Ca2+, Ca2+/calmodulin-dependent protein kinase II (CaMKII), and protein-kinase A (PKA) revealed that dopamine only activated PKA when preceded by APs, and then PKA activated CaMKII through the dopamine- and cAMP-regulated phosphoprotein 32 kDa (DARPP-32); thus dopamine regulated the degree of structural plasticity. In thin distal dendrites, where spines localize, the time window for PKA activation was narrow due to greater activity of phosphodiesterases (PDEs), which prevented accumulation of cAMP, unless dopamine was preceded by APs. Our results clarify the biological basis of reinforcement learning at the single spine level and reveal the interrelationship between Hebbian and reinforcement plasticity.

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