Revisiting and Revising Memory Consolidation: Personal Reflections on the Research Legacy of Ivan Izquierdo

Two important themes in Ivan Izquierdo's research each offered both answers and questions about the topic of memory formation and maintenance. The first theme provided evidence supporting the view that short- and long-term memory were distinct processes and could be selectively modulated by several treatments, with some affecting only short-term, others only affecting long-term memory, and still others affecting both. Over many years, Izquierdo's laboratory documented molecular responses across time after training obtaining results that showed differences as well as similarities in the biochemical changes during the first 1-2 h and the next 4-6 h after training, i.e., during the transition from short- to long-term memory. This work clarified the biological underpinnings of the memory processes. The second theme described waves of susceptibility of memory to enhancing and impairing treatments after time, a biphasic profile that contrasted with earlier monotonic decreases in the efficacy of memory modulating treatments as a function of time between training and treatment. Remarkably, these waves of susceptibility to modification were accompanied by biphasic changes in molecular measures at similar times after training. Remarkably, some of the molecular players exhibited persistent changes after training, with increases in levels lasting days following the training experience. These persistent molecular changes may reveal a biological basis for the dynamic nature of memories seen long after the initial memory is consolidated.