Acquisition of Response Thresholds for Timed Performance is Regulated by a Calcium-Responsive Transcription Factor, CaRF

AGOSTINO P.V.; R.-K. CHENG; C.L. WILLIAMS; A.E. WEST; MECK W.H.

GENES BRAIN AND BEHAVIOR

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2013 vol. 12 p. 633 - 644

1601-1848

Interval timing within the seconds-to-minutes range involves the interaction of the prefrontal cortex and basal ganglia via dopaminergic-glutamatergic pathways. Because the secreted protein BDNF is able to modulate dopamine release as well as glutamatergic activity, we hypothesized that BDNF may be important for these timing mechanisms. Recently the transcription factor CaRF was identified as an important modulator of BDNF expression in the cerebral cortex. In the present study, a strain of Carf knockout mice were evaluated for their ability to acquire the "Start" and "Stop" response thresholds under sequential and simultaneous training conditions, using multiple (15-s and 45-s) or single (30-s) target durations using the peak-interval procedure. Both Carf+/- and Carf-/- mice were impaired in their ability to acquire timed response thresholds relative to Carf+/+ mice. These results suggest that the inhibitory processes required to set response thresholds and exert temporal control of behavior may be dependent on CaRF regulation of genes including Bdnf in cortico-striatal circuits.