Each day we learn and remember a myriad of new information from the names of new people we meet to the best dish to order at a particular restaurant to the location of a new bike path. This novel information is first acquired, and if strengthened through a process called consolidation, is eventually stored in long-term memory. The structures of the medial temporal lobe are essential for this ability to acquire new long-term memories for facts and events. This form of memory is called declarative memory in humans and relational memory in animals. Convergent findings from neuropsychological studies in humans, together with experimental lesion studies and neuroanatomical studies in animals have shown that the key medial temporal lobe structures important for declarative/relational memory include the hippocampus together with the surrounding entorhinal, perirhinal and parahippocampal cortices. While it is clear that the structures of the medial temporal lobe are essential for the acquisition of new declarative/relational memories, we still have only a rudimentary understanding of the normal patterns of neural activity that underlie this ability. To start to address this question, my laboratory has recorded the activity of individual neurons in the hippocampus as monkeys perform various memory demanding tasks. We have focused on one particular form of declarative/relational memory, called associative memory, which is defined as the ability to learn and remember the relationship between unrelated items such as the name of someone we have just met or the aroma of a particular perfume. Specifically, we examined the patterns of activity in hippocampal neurons as monkeys are in the process of forming new associations in memory. We hypothesized that if the hippocampus is important for the early formation of the new associations, we should see changes in neural activity that parallel behavioral learning. Our long-term goal is to understand the evolution of learning-related signals throughout the medial temporal lobe as memories are initially established, strengthened and eventually stored in long-term memory.
A Task Requiring New Associative Leaning
To examine the patterns of neural activity during associative memory formation, we trained two monkeys to perform a location-scene association task. In this task, animals were required to learn new associations between particular complex visual "scenes" and particular rewarded target locations. We know that the medial temporal lobe participates importantly in the normal performance of this task since damage to this region in monkeys produces significant impairment in the ability to learn new location-scene associations (Brasted et al., 2003; Brasted et al., 2002; Murray et al., 2000; Wise and Murray, 1999; Murray and Wise, 1996; Rupniak and Gaffan, 1987). A schematic representation of the task is shown in Figure 1. On each trial, monkeys are first shown 4 identical target stimuli superimposed on a complex visual scene (typically a picture of a real outdoor scene). Following a delay interval, during which the scene disappears but the targets remain on the screen, the animal is cued to make a single eye movement to one of the four peripheral targets on the screen. For each visual scene, only one of the 4 targets is associated with a juice reward. Each day, the animals learned 2-4 new location-scene associations by trial and error. The new location-scene associations were randomly intermixed with well-learned "reference" associations that the animals had seen for many months before the recording experiments began. Each of the 4 reference scenes was associated with a different rewarded target location (i.e., north, south, east or west). Responses to the reference scenes were used to control for possible motor-related activity in hippocampal cells.