Communication between the medial frontal cortex and mediodorsal thalamus is required for timing performance in rats

Predicting when future events will occur is critical for adaptive behavior, yet the brain networks underlying this ability remain unclear. The prefrontal cortex (PFC) and its rodent analogue, the prelimbic cortex (PL), are known to support the ability to track time and execute decisions in anticipation of upcoming events. Given this, we can expand our understanding of the circuits involved in time-based behavior by looking for regions that interact with the PFC during timing tasks. The mediodorsal nucleus of the thalamus (MD) is a strong candidate, as it shares dense reciprocal connections with the PFC and is widely implicated in higher-order cognition. However, data implicating the. MD itself in timing is still minimal, and to our knowledge, causal data directly implicating MD-PFC communication in timing is lacking entirely. To address this, we trained nineteen male Long Evans rats on a dual interval timing task requiring decision-making and tested the effects of reversibly inactivating the MD/PL individually or blocking communication between them using GABA-A receptor agonist, muscimol. All manipulations produced a similar deficit-flattening the characteristic Gaussian-shaped reponse curves while leaving overall response rates intact. Single-trial analyses revealed that this was not simply a broadening of temporally-controlled response bursts, but rather a fundatment breakedown in the canonical burst structure of timing behavior, with responses becoming more uniflormly distrubted across the trial. These findings further implicate the MD and PL in timing and, to our knowledge, provide the first causal evidence that communication between the MD and PFC is specifically required. More broadly, these findings add to growing evidence that MD-PFC interactions support higher-order cognition. Timing impairments are common in a variety of neuropsychiatric diseases including schizophrenia, Parkinson's disease, autism, and bipolar disorder so this work provides key implications for the involvement of a novel MD-PFC pathway.