The Bilateral Prefronto-striatal Pathway Is Necessary for Learning New Goal-Directed Actions

Curr Biol. 2018 Jul 23;28(14):2218-2229.e7. doi: 10.1016/j.cub.2018.05.028. Epub 2018 Jun 28.


The acquisition of new goal-directed actions requires the encoding of action-outcome associations. At a neural level, this encoding has been hypothesized to involve a prefronto-striatal circuit extending between the prelimbic cortex (PL) and the posterior dorsomedial striatum (pDMS); however, no research identifying this pathway with any precision has been reported. We started by mapping the prelimbic input to the dorsal and ventral striatum using a combination of retrograde and anterograde tracing with CLARITY and established that PL-pDMS projections share some overlap with projections to the nucleus accumbens core (NAc) in rats. We then tested whether each of these pathways were functionally required for goal-directed learning; we used a pathway-specific dual-virus chemogenetic approach to selectively silence pDMS-projecting or NAc-projecting PL neurons during instrumental training and tested rats for goal-directed action. We found that silencing PL-pDMS projections abolished goal-directed learning, whereas silencing PL-NAc projections left goal-directed learning intact. Finally, we used a three-virus approach to silence bilateral and contralateral pDMS-projecting PL neurons and again blocked goal-directed learning. These results establish that the acquisition of new goal-directed actions depends on the bilateral PL-pDMS pathway driven by intratelencephalic cortical neurons.

Keywords: CLARITY; dorsomedial striatum; goal-directed action; goal-directed learning; instrumental conditioning; intratelencephalic neurons; outcome devaluation; prelimbic cortex; pyramidal tract neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conditioning, Operant*
  • Corpus Striatum / physiology*
  • Learning / physiology*
  • Male
  • Neural Pathways / physiology*
  • Prefrontal Cortex / physiology*
  • Pyramidal Tracts / physiology
  • Rats
  • Rats, Long-Evans
  • Rats, Wistar
  • Telencephalon / physiology