University of Vermont COBRE (P20 RR016435)
"Center for Neuroscience Excellence"

Pilot Project 3: "Hippocampal Activity During Blocking and Unblocking"
Investigator: John Green, Ph.D.

Decades of research have revealed that the hippocampus is a key brain structure required for many types of learning and memory. However, there is considerable disagreement about exactly when, how, and why the hippocampus is required. Eyeblink classical conditioning procedures using rats as subjects are particularly useful for addressing these questions because the brain substrates of the basic task are well understood. In basic, "delay" conditioning, a neutral stimulus, such as a tone, consistently precedes, and overlaps with, eyelid stimulation. Learning is revealed by responses made to the tone (in this case, eye blinks) in anticipation of the eyelid stimulation. Delay eyeblink conditioning requires only a brainstem-cerebellar circuit. In contrast, trace eyeblink conditioning, in which the neutral stimulus precedes, but does not overlap with, eyelid stimulation, requires the hippocampus, in addition to the brainstem-cerebellar circuit. It is unclear why the hippocampus is required for trace conditioning, and how it communicates with the cerebellum. The goal of this project is to compare activation patterns of hippocampal and cerebellar neurons during delay versus trace conditioning. Since delay conditioning does not require the hippocampus, and both delay and trace conditioning require the cerebellum, this study will provide new data on the unique hippocampal role during trace conditioning. Future studies will be directed towards understanding how the hippocampus interacts with the cerebellum during learning. A full understanding of hippocampal engagement during learning and memory is crucial, in order to understand how to ameliorate the many memory deficits associated with hippocampal dysfunction.