Memory on time

Abstract

Considerable recent work has shown that the hippocampus is critical for remembering the order of events in distinct experiences, a defining feature of episodic memory. Correspondingly, hippocampal neuronal activity can 'replay' sequential events in memories and hippocampal neuronal ensembles represent a gradually changing temporal context signal. Most strikingly, single hippocampal neurons - called time cells - encode moments in temporally structured experiences much as the well-known place cells encode locations in spatially structured experiences. These observations bridge largely disconnected literatures on the role of the hippocampus in episodic memory and spatial mapping, and suggest that the fundamental function of the hippocampus is to establish spatio-temporal frameworks for organizing memories.

Figure 1

Involvement of the hippocampus in the temporal organization of memory in humans and rats. (a) Left: memory for serial order in lists. Middle: activation of the hippocampus in humans remembering the order of scenes in a movie. Reproduced, with permission, from [9]. Right: performance of normal rats and rats with selective hippocampal damage on memory for the order of odors versus recognition of odors from a list (p = 0.009). Reproduced, with permission, from [13]. (b) Left: disambiguation of overlapping sequences. Red and blue arrows indicate the two sequences. Middle: activation of the hippocampus during learning of overlapping face sequences. Reproduced, with permission, from [23]. Right: firing patterns of a hippocampal neuron as a rat traverses the maze stem on left-turn (blue dots represent spikes) and right-turn (red dots) trials. Gray lines are paths through the maze on both types of trials. Reproduced, with permission, from [41].

Figure 2

Models of temporal representation in the hippocampus. (a) Firing chain model of Mehta et al.[33]. As a rat moves consistently from left to right (arrow), CA3 place cells that fire in order (orange dots) activate a CA1 cell, and the strength of each synapse is proportional to the thickness of the red lines. After repeated directional activation, LTP of the CA3-to-CA1 synapses results in a synaptic matrix that is asymmetric (blue lines and blue curve). Reproduced, with permission, from [33]. (b) Temporal context model of Wallenstein et al. [35]. At the top are spiking patterns of different neurons representing 13 items that occur sequentially; at the bottom are longer firing context neurons that bridge across items within the sequence. Reproduced, with permission, from [35].

Figure 3

Time cells in the hippocampus. Above: in the object-delay-odor sequence task, rats are initially presented with one of two objects and then, following a 10 sec delay, must respond to one of two odors to receive reward. Below: during the delay, hippocampal neurons fire sequentially; the normalized firing rate of each neuron is shown in successive rows. Reproduced, with permission, from [50].