Medial Auditory Thalamus Is Necessary for Expression of Auditory Trace Eyelid Conditioning.

Transforming a brief sensory event into a persistent neural response represents a mechanism for linking temporally disparate stimuli together to support learning. The cerebellum requires this type of persistent input during trace conditioning to engage associative plasticity and acquire adaptively timed conditioned responses (CRs). An initial step toward identifying the sites and mechanisms generating and transmitting persistent signals to the cerebellum is to identify the input pathway. The medial auditory thalamic nuclei (MATN) are the necessary and sufficient source of auditory input to the cerebellum for delay conditioning in rodents and a possible input to forebrain sites generating persistent signals. Using pharmacological and computational approaches, we test (1) whether the necessity of MATN during auditory eyelid conditioning is conserved across species, (2) whether the MATN are necessary for the expression of trace eyelid CRs, and if so, (3)whether this relates to the generation of persistent signals. We find that contralateral inactivation of MATN with muscimol largely abolished trace and delay CRs in male rabbits. Residual CRs were decreased in amplitude, but CR timing was unaffected. Results from large-scale cerebellar simulations are consistent with previous experimental demonstrations that silencing only CS-duration inputs does not abolish trace CRs, and instead affects their timing. Together, these results suggest that the MATN are a necessary component of both the direct auditory stimulus pathway to the cerebellum and the pathway generating task-essential persistent signals.SIGNIFICANCE STATEMENT Persistent activity is required for working memory-dependent tasks, such as trace conditioning, and represents a mechanism by which sensory information can be used over time for learning and cognition. This neuronal response entails the transformation of a discrete sensory-evoked response into a signal that extends beyond the stimulus event. Understanding the generation and transmission of this stimulus transformation requires identifying the input sources necessary for task-essential persistent signals. We report that the medial auditory thalamic nuclei are required for the expression of auditory trace conditioning and suggest that these nuclei are a component of the pathway-generating persistent signals. Our study provides a foundation for testing circuit-level mechanisms underlying persistent activity in a cerebellar learning model with identified inputs and well defined behavioral outputs.