Towards a functional organization of episodic memory in the medial temporal lobe

Abstract

Here we describe a model of medial temporal lobe organization in which parallel "what" and "where" processing streams converge within the hippocampus to represent events in the spatio-temporal context in which they occurred; this circuitry also mediates the retrieval of context from event cues and vice versa, which are prototypes of episodic recall. Evidence from studies in animals are reviewed in support of this model, including experiments that distinguish characteristics of episodic recollection from familiarity, neuropsychological and recording studies that have identified a key role for the hippocampus in recollection and in associating events with the context in which they occurred, and distinct roles for parahippocampal region areas in separate "what" and "where" information processing that contributes to recollective and episodic memory.

Figure 1

Ideal ROC functions for human recognition memory predicted by Dual Process Signal Detection (DPSD) theory (see Yonelinas, 2001) and observed ROC functions for recognition memory in rats. a–c. Humans. a. Item recognition. The ROC curve is typically asymmetrical and curvilinear. Quantitiative measurements of the contributions of recollection (R) and familiarity (F) are calculated as probability estimates shown in the inset of this and other figures (see Yonelinas et al., 2002). b. ROC function observed when performance is based only on recollection. c. ROC function observed when performance is based only on familiarity. d–f. Rats. d. Item recognition (data from Fortin et al., 2004). Recollection and familiarity components are both robust, similar to the ideal item recognition ROC in humans (Panel a.). e. Associative recognition (data from Sauvage et al., 2008). The ROC becomes linear, similar to the ideal ROC of humans when performance is based on recollection only (panel b). f. Item recognition with a speeded response deadline demand (data from Sauvage et al., 2010a). The ROC becomes symmetrical and curvilinear, similar to the ideal ROC of humans when performance is based on familiarity only (Panel c).

Figure 2

Schematic diagram of the medial temporal lobe memory system in mammals. The “where” stream of the neocortex projects differentially to the perirhinal cortex (PRC) and lateral entorhinal area (LEA), whereas the “what” stream of the neocortex projects differentially to the parahippocampal cortex (PHC) and medial entorhinal area (MEA). In those parahippocampal regions, the PRC-LEA represents individual objects (items), whereas the PHC-MEA represents contextual information. Those streams converge in the hippocampus where items are represented in the context in which they were experienced. Outputs of the hippocampus are directed back to the parahippocampal areas, and then the neocortical areas, that were the origins of the “what” and “where” stream inputs.

Figure 3

The hippocampus and “what,” “where,” “when” memory. a. Behavioral protocol. b. Control rats make an initial good guess about which item occurred first (“when”) based on location information (“where”) and then they confirmed or disconfirmed their choice based on the odor in the cup (“what”). c. Rats with hippocampal damage perform at chance level on the final choice and below chance in their first visit.

Figure 4

Hippocampal neurons develop item-place representations in parallel with learning what happens where. a. Object-context association task. The two contexts (represented by different shadings) differed in their flooring and wallpaper. The stimulus items (X or Y) differed in odor and in the medium that filled the pots. Items with a plus contained reward, whereas those with a minus did not, each depending upon the spatial context. b. Changes in proportions of Item-Position and Position cells in learning vs. c. overtraining sessions.

Figure 5

Spatial firing rate plots for example neurons in CA1 and MEC in rats performing a T-maze alternation task. Left panels show firing rate plots for right-to-left trials and right panels show firing rates plots for left-to-right trials. Each trial begins when the rat leaves the reward site (small light-blue circles) on the left or right side of the T-maze (outlined in white), then the rat runs down the start arm, turns into and traverses the central stem, then turns in the direction opposite to the start arm to receive a reward. Note the animal occupies only the central stem on all trials, such that comparisons of firing patterns between left-to-right and right-to-left trials focus on that area alone. Red = highest normalize firing rate; blue = zero firing rate.