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Front. Integr. Neurosci. | doi: 10.3389/fnint.2018.00020

Inactivation of the medial-prefrontal cortex impairs interval timing precision, but not timing accuracy or scalar timing in a peak-interval procedure in rats

 Catalin V. Buhusi1, 2*, Marcelo Reyes2, Cody A. Gathers2,  Sorinel A. Oprisan3 and  Mona Buhusi1, 2
  • 1Dept. Psychology, Utah State University, United States
  • 2Dept. Neurosciences, Medical University of South Carolina, United States
  • 3Department of Physics and Astronomy, College of Charleston, United States

Motor sequence learning, planning and execution of goal-directed behaviors, and decision making rely on accurate time estimation and production of durations in the seconds-to-minutes range. The pathways involved in planning and execution of goal-directed behaviors include cortico-striato-thalamo-cortical circuitry modulated by dopaminergic inputs. A critical feature of interval timing is its scalar property, by which the precision of timing is proportional to the timed duration. We examined the role of medial prefrontal cortex (mPFC) in timing by evaluating the effect of its reversible inactivation on timing accuracy, timing precision, and scalar timing. Rats were trained to time two durations in a peak-interval procedure. Reversible mPFC inactivation using GABA agonist muscimol resulted in decreased timing precision, with no effect on timing accuracy and scalar timing. These results are partly at odds with studies suggesting that ramping prefrontal activity is crucial to timing, but are closely match simulations with the Striatal Beat Frequency (SBF) model proposing that timing is coded by the coincidental activation of striatal neurons by cortical inputs. Computer simulations indicate that in SBF, gradual inactivation of cortical inputs results in a gradual decrease in timing precision with preservation of timing accuracy and scalar timing. Further studies are needed to differentiate between timing models based on coincidence detection and timing models based on ramping mPFC activity, and clarify whether mPFC is specifically involved in timing, or more generally involved in attention, working memory, or response selection/inhibition.

Keywords: interval timing, medial prefrontal cortex (mPFC), Pharmacology, Muscimol, computational modeling, Rats, Sprague-Dawley, Striatal beat frequency model

Received: 16 Feb 2018; Accepted: 09 May 2018.

Edited by:

Hugo Merchant, Universidad Nacional Autónoma de México, Mexico

Reviewed by:

Pavel E. Rueda-Orozco, Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Mexico
Yves Boubenec, École Normale Supérieure, France  

Copyright: © 2018 Buhusi, Reyes, Gathers, Oprisan and Buhusi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Catalin V. Buhusi, Utah State University, Dept. Psychology, 2810 Old Main Hill, Logan, 84322-2810, UT, United States,