The ultimate purpose of studying the cellular mechanisms and reviewing behavioral observations is to come up with a functional description of the architecture that supports memory. Unfortunately progress at this front is rather slow. The independent findings are yet to be combined with a model of how things work together. However, in this section, I will review the current findings about the architecture of memory.
Fuster and Jervey showed that temporal lobe structures that are involved in
encoding visual information during perception are also involved in storing that
information
[Fuster and Jervey, 1982]. This clearly suggests that different types of
information are stored differently. If perceptual structures also serve to
store information, properties of memory function must be understood within the
context of the perceptual function. Specifically they recorded single unit
activity with microelectrodes in macaque monkeys performing a visual delayed
matching-to-sample task. During the delay, a substantial contingent of cells
showed increased, sustained, and in some cases, color-dependent discharge.
Fuster and Jervey propose that these cells are engaged in temporary retention
of the sample stimulus.
Miyashita and Chang performed a similar study using complex visual stimuli
[Miyashita and Chang, 1988]. They found a group of shape-selective neurons in an
anterior ventral part of the temporal cortex of monkeys that exhibit sustained
activity during the delay period of a visual short term memory task. They
observed that the activity was highly selective for the pictorial information
to be memorized and was independent of the physical attributes such as size,
orientation, color, or position of the object. These observations suggest that
the delay activity represents the short-term memory of the categorized percept
of a picture. Another evidence for the storage of visual memory traces in the
temporal lobes is that electric stimulation of this area in humans result in
recall of imagery.
Gnadt and Andersen showed that memory representations used to guide eye movements are represented at least in part in posterior parietal cortical areas that are used in motor control [Gnadt and Andersen, 1988]. They performed studies in the rhesus monkey during tasks which required saccadic eye movements to remembered target locations in the dark. Neurons in the lateral bank of the intraparietal cortex were found which remained active during the time period for which the monkey had to withhold eye movements while remembering desired target locations. The activity of the cells was tuned for eye movements of specific direction and amplitude, and it was not necessary for a visual stimulus to fall within the response field. The study suggests that the activity of these neurons represent the intent to make eye movements of specific direction and magnitude.
Funahashi and colleagues showed that the dorsolateral prefrontal area (Area 46) contains a structure that codes the spatial locations of stimuli [Funahashi et al., 1989]. This area is very close to the frontal eye fields (Area 8), which play a critical role in planned sequences of eye movements. The area Funahashi studied is spatially organized and has precise connections to the regions of the parietal lobe studied by Gnadt and Andersen. These two studies might be uncovering a combined front-parietal system that codes the locations of the objects and directs eye movements to selected locations.
The studies mentioned so far all focus on the short term memory and stress the fact that the areas of the brain that do the processing also do the storing of information. The long term memory, however, is a different story. The data from disorders indicate several candidate regions of the brain as related to general memory processes. These are anterior temporal cortex, the medial temporal region, medial thalamus, mamillary bodies, and basal forebrain. The interactions between these regions are still speculative. However several models have started to emerge from animal and human studies.
Mishkin outlined the architecture of an entire memory system based on findings from animal studies [Mishkin, 1982]. He theorized about the possible role of the hippocampus and related structures in a model of interacting components. Mishkin postulates that coded representations of stimuli are stored in the higher-order sensory areas of the cortex whenever stimulus activation of these areas also triggers a cortico-limbo-thalamo-cortical circuit. He proposed that the role of this circuit could be either imprinting or rehearsal of the stimuli. The representation stored in the cortex is used for three distinct tasks: recognition, which occurs when the stored representation is reactivated via the original sensory pathway; recall, when it is reactivated via any other pathway; and association, when it activates other stored representations via the outputs of the higher order sensory areas to the relevant structures.
Squire revised Mishkin's model based on the more recent evidence that emphasizes the role of the entorhinal and related cortex and de-emphasizes the role of the amygdala [Squire, 1989]. The entorhinal cortex is the gateway to the hippocampus, and receives input from all of the perceptual systems. Many of its neurons respond selectively to stimuli in multiple sensory modalities. Thus architecturally it has a unique location that would support combining inputs from various sensory modalities. Studies have shown that removal of hippocampus and medial temporal cortex produced severe amnesia, even if the amygdala is preserved.
Another problem with Mishkin's model is that it does not have a clear explanation of how the consolidation process works. Thus it is vague on the question of retrograde amnesia. In an experiment by Sutherland and Arnold, rats were trained to find a hidden location in the Morris Water Task [Sutherland and Arnold, 1987]. The animals were then kept in their cages for 1, 4, 8 or 12 weeks before producing hippocampal damage in different groups. All groups were tested two weeks after the surgery. The finding was that the longer the period between learning and hippocampal damage, the better the performance. This experiment suggests that hippocampus is transiently involved in the memory storage process and that other structures maintain the permanent memories.
Recent work by Wilson and McNaughton hints at interesting possibilities for the role of the hippocampus in consolidation [Wilson and McNaughton, 1994]. They developed a technique by which they can record simultaneously from about a hundred neurons in a rat hippocampus. Their recordings as the rat traversed a new environment confirmed the existence of cells in the hippocampus that are sensitive to particular locations in the environment regardless of orientation or other sensory stimuli. The more interesting observation was the recordings made during the slow-wave sleep preceding and following the behavior. Cells that fired together when the animal occupied particular locations in the environment exhibited an increased tendency to fire together during subsequent sleep, in comparison to sleep episodes preceding the behavioral tasks. Cells that were inactive during behavior, or that were active but had non-overlapping spatial firing, did not show this increase. This suggests that information acquired during active behavior may be re-expressed in hippocampal circuits during sleep, possibly supporting memory consolidation.
It is interesting to note the rapid evolution of the role assigned to the hippocampus in the last half a century [Swanson, 1983]. The first hypothesis was the notion that the hippocampus has a primarily olfactory function. It was called the rhinencephalon or ``smell brain''. In 1947 Brodal demolished this view by pointing out that conditioned olfactory behavior was not effected by hippocampal ablations, and several anosmotic mammals the hippocampus is well developed. In 1937 Papez proposed based on anatomical evidence that the circuit interrelating the hippocampus, the mammillary body, the anterior thalamic nuclei and the cingulate gyrus could be the basis for emotional behavior. In 1952, MacLean proposed the term ``limbic system'' to refer to this complex of structures and the related circuitry. He later elaborated by suggesting that there is a basic dichotomy between the ``old'' (limbic) and the ``new'' cortex, the former supporting emotional (what we feel) and the latter supporting the cognitive (what we know) functions. The third major hypothesis was prompted by Scoville and Milner's description of patient H. M. in 1957. A large body of animal research since then showed that hippocampal ablations interfere with a variety of learning and memory tasks, that hippocampus contains place units (Hebb's cognitive map of the external world), and it was involved primarily in learning tasks that rely heavily on spatial cues. [O'Keefe and Nadel, 1978].
A more recent review by Eichenbaum and colleagues [Eichenbaum et al., 1992], addresses four questions about the hippocampus: What is the fundamental nature of memory supported by the hippocampal system, what is the contribution of the hippocampus itself among closely related structures to memory, how is information encoded by the activity of hippocampal neurons, and does hippocampus actually store memories. It is pointed out that across species and across learning materials the hippocampal system is critical to declarative memory. This kind of memory differs from hippocampal-independent type by its relational representation and representational flexibility. It is evident that hippocampus itself is one component in a large circuit that includes Ammon's horn, the dentate gyrus, the subiculum, and other areas. Hippocampus receives inputs from several functionally distinct brain areas. Thus the neural activity in the hippocampus presumably reflects all types of sensory and behavioral events, and in particular the relationship between those events. They seem to process properties of stimulus events related to their functional significance, in particular, neuronal activity does not depend on the presence of any particular component of the items they represent. It is also known that hippocampal neurons act as members of a distributed network, and their ensemble activity supports the memories. The hippocampus itself does not store memories permanently, although it keeps them for some variable time after the learning event. It probably functions as an enabler of memory storage in neocortical storage sites.