Hippocampal theta-dependent eyeblink classical conditioning: Coordination of a distributed learning system

Richard F. Thompson’s study of the neurobiological substrates of learning and memory has been a career-long endeavor, chosen early and pursued with uncompromising depth and breadth. His systematic mapping of the major brain systems and mechanisms involved in eyeblink classical conditioning (EBCC) established the essential role of the cerebellum. Investigations of the interactions between the hippocampus and cerebellum are critically important to this literature, given the essential involvement of these structures in trace EBCC as well as an important modulatory role of the hippocampus in delay EBCC. Hippocampal theta (3–7 Hz) oscillations are known to reflect a functional state that influences both the timing of unit firing and the potential for neural plasticity in the hippocampus and other structures. Herein we present a brief summary of research demonstrating the behavioral enhancement due to theta and the underlying neurobiological correlates in both hippocampus and cerebellum during EBCC. Hippocampal and cerebellar local field potentials (LFPs) show that these distantly interconnected brain structures become precisely synchronized when conditions favor rapid behavioral acquisition. Our results suggest a major role for theta in coordinating the widely distributed memory system for trace EBCC. These and other important findings reflect Thompson’s own work and his early-career mentoring of scientists whose contributions to the EBCC literature have ensured his major and lasting impact on the neurobiology of learning and memory.

Research highlights
► We review our research on hippocampal theta-contingent eyeblink conditioning.
► Training trials presented during hippocampal theta substantially increase learning rate.
► Theta modulates both delay and trace conditioning and improves age-related deficits.
► Pretrial theta leads to hippocampal–cerebellar synchronization at theta frequency.
► We celebrate R.F. Thompson’s unique contribution to the neurobiology of learning.