PT  - JOURNAL ARTICLE
AU  - Melissa Malvaez
AU  - Venuz Y. Greenfield
AU  - Dina P. Matheos
AU  - Nicolas A. Angelillis
AU  - Michael D. Murphy
AU  - Pamela J. Kennedy
AU  - Marcelo A. Wood
AU  - Kate. M. Wassum
TI  - Habits are negatively regulated by HDAC3 in the dorsal striatum
AID  - 10.1101/153734
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 153734
4099  - http://biorxiv.org/content/early/2017/06/21/153734.short
4100  - http://biorxiv.org/content/early/2017/06/21/153734.full
AB  - Optimal behavior results from a balance of control between two strategies, one cognitive/goal-directed and one habitual, which rely on the anatomically distinct dorsomedial (DMS) and dorsolateral (DLS) striatum, respectively. The transcriptional regulatory mechanisms required to learn and transition between these strategies are unknown. Here we identified a critical negative regulator of habit learning. Histone deacetylase (HDAC) inhibition following instrumental conditioning accelerated habitual control of behavior. HDAC3, a transcriptional repressor, was removed from the promoters of learning-related genes in the dorsal striatum as habits formed with overtraining and with post-training HDAC inhibition. Decreasing HDAC3 function in the DLS accelerated habit formation, while DLS HDAC3 overexpression prevented habit. HDAC3 activity in the DMS was also found to constrain habit formation. These results challenge the strict dissociation between DMS and DLS function in goal-directed v. habitual behavioral control and identify dorsal striatal HDAC3 as a critical molecular substrate of the transition to habit.