Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 21, Pages 6718-6723Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1507121112
Keywords
in vivo FRET imaging; microendoscope; dorsal striatum; action selection; mating behavior
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [22220005, 24111552, 22300136, 26560470, 22113002]
- Grants-in-Aid for Scientific Research [26113720, 13J04607, 26560470, 24111552, 22113002, 26830070, 22113001, 22220005, 22300136] Funding Source: KAKEN
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The selection of reward-seeking and aversive behaviors is controlled by two distinct D1 and D2 receptor-expressing striatal medium spiny neurons, namely the direct pathway MSNs (dMSNs) and the indirect pathway MSNs (iMSNs), but the dynamic modulation of signaling cascades of dMSNs and iMSNs in behaving animals remains largely elusive. We developed an in vivo methodology to monitor Forster resonance energy transfer (FRET) of the activities of PKA and ERK in either dMSNs or iMSNs by microendoscopy in freely moving mice. PKA and ERK were coordinately but oppositely regulated between dMSNs and iMSNs by rewarding cocaine administration and aversive electric shocks. Notably, the activities of PKA and ERK rapidly shifted when male mice became active or indifferent toward female mice during mating behavior. Importantly, manipulation of PKA cascades by the Designer Receptor recapitulated active and indifferent mating behaviors, indicating a causal linkage of a dynamic activity shift of PKA and ERK between dMSNs and iMSNs in action selection.
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