Neurobiology of spatial memory

Hippocampus
The hippocampus provides animals with a spatial map of their environment. It stores information regarding non-egocentric space (egocentric means in reference to one's body position in space) and therefore supports viewpoint independence in spatial memory. This means that it allows for viewpoint manipulation from memory. It is however, important for long-term spatial memory of allocentric space (reference to external cues in space). Maintenance and retrieval of memories are thus relational or context dependent. The hippocampus makes use of reference and working memory and has the important role of processing information about spatial locations.

Blocking plasticity in this region results in problems in goal-directed navigation and impairs the ability to remember precise locations. Amnesic patients with damage to the hippocampus cannot learn or remember spatial layouts and patients having undergone hippocampal removal are severely impaired in spatial navigation. Monkeys with leisons to this area cannot not learn object-place associations and rats also display spatial deficits by not reacting to spatial change. In addition, rats with hippocampal lesions were shown to have temporally ungraded (time-independent) retrograde amnesia that is only resistant to recognition of a learned platform task when the entire hippocampus is lesioned but not when it is partially lesioned. Deficits in spatial memory are also found in spatial discrimination tasks.

Large differences in spatial impairment are found among the dorsal and ventral hippocampus. Lesions to the ventral hippocampus have no effect on spatial memory, while the dorsal hippocampus is required for retrieval, processing short-term memory and transferring memory from the short term to longer delay periods. Infusion of amphetamine into the dorsal hippocampus has also been shown to enhance memory for spatial locations learned previously. These findings indicate that there is a functional dissociation between the dorsal and ventral hippocampus.

Hemispheric differences within the hippocampus are also observed. A study on London taxi drivers, asked drivers to recall complex routes around the city as well as famous landmarks for which the drivers had no knowledge of their spatial location. This resulted in an activation of the right hippocampus solely during recall of the complex routes which indicates that the right hippocampus is used for navigation in large scale spatial environments.

The hippocampus is known to contain two separate memory circuits. One circuit is used for recollection-based place recognition memory and includes the entorhinal-CA1 system while the other system is used for place recall memory and makes use of the CA3-CA1 system.

Place cells are also found in the hippocampus.

Posterior parietal cortex
The parietal cortex encodes spatial information using an egocentric frame of reference. It is therefore involved in the transformation of sensory information coordinates into action or effector coordinates by updating the spatial representation of the body within the environment. As a result, lesions to the parietal cortex produce deficits in the acquisition and retention of egocentric tasks, whereas minor impairment is seen among allocentric tasks.

Rats with lesions to the anterior region of the posterior parietal cortex reexplore displaced objects, while rats with lesions to the posterior region of the posterior parietal cortex displayed no reaction to spatial change.

Parietal cortex lesions are also known to produce temporally ungraded retrograde amnesia.

Entorhinal cortex
The dorsalcaudal medial entorhinal cortex (dMEC) contains a topographically organized map of the spatial environment made up of grid cells. This brain region thus transforms sensory input from the environment and stores it as a durable allocentric representation in the brain to be used for path integration.

The entorhinal cortex contributes to the processing and integration of geometric properties and information in the environment. Lesions to this region impair the use of distal but not proximal landmarks during navigation and produces a delay-dependent deficit in spatial memory that is proportional to the length of the delay. Lesions to this region are also known to create retention deficits for tasks learned up to 4 weeks but not 6 weeks prior to the lesions.

Memory consolidation in the entorhinal cortex is achieved through extracellular signal-regulated kinase activity.

Prefrontal cortex
The medial prefrontal cortex processes egocentric spatial information. It participates in the processing of short-term spatial memory used to guide planned search behavior and is believed to join spatial information with its motivational significance. The identification of neurons that anticipate expected rewards in a spatial task support this hypothesis. The medial prefrontal cortex is also implicated in the temporal organization of information.

Hemisphere specialization is found in this brain region. The left prefrontal cortex preferentially processes categorical spatial memory including source memory (reference to spatial relationships between a place or event), while the right prefrontal cortex preferentially processes coordinate spatial memory including item memory (reference to spatial relationships between features of an item).

Leisons to the medial prefrontal cortex impair the performance of rats on a previously trained radial arm maze, however, rats can gradually improve to the level of the controls as a function of experience. Lesions to this area also cause deficits on delayed nonmatching-to-positions tasks and impairments in the acquisition of spatial memory tasks during training trials.

Retrosplenial cortex
The retrosplenial cortex is involved in the processing of allocentric memory and geometric properties in the environment. Inactivation of this region accounts for impaired navigation in the dark and thus it is implicated to be involved in the process of path integration.

Lesions to the retrosplenial cortex consistently impair tests of allocentric memory, while sparing egocentric memory. Animals with lesions to the caudal retrosplenial cortex show impaired performance on a radial arm maze only when the maze is rotated to remove their reliance on intramaze cues. In humans, damage to the retrosplenial cortex results in topographical disorientation. Most cases involve damage to the right retrosplenial cortex and include Broadmann’s area 30. Patients are often impaired at learning new routes and at navigating through familiar environments. However, most patients usually recover within 8 weeks.

The retrosplenial cortex preferentially processes spatial information in the right hemisphere.

Perirhinal cortex
The perirhinal cortex is associated with both spatial reference and spatial working memory. It processes relational information of environmental cues and locations.

Lesions in the perirhinal cortex account for deficits in reference memory and working memory, and increase the rate of forgetting of information during training trials of the Morris water maze. This accounts for the impairment in the initial acquisition of the task. Lesions also cause impairment on an object location task and reduce habituation to a novel environment.

Plasticity
Spatial memories are formed after an animal gathers and processes sensory information about its surroundings (especially vision and proprioception). In general, mammals require a functioning hippocampus (particularly area CA1) in order to form and process memories about space. There is some evidence that human spatial memory is strongly tied to the right hemisphere of the brain.

Spatial learning requires both NMDA and AMPA receptors, consolidation requires NMDA receptors, and the retrieval of spatial memories requires AMPA receptors. In rodents, spatial memory has been shown to covary with the size of a part of the hippocampal mossy fiber projection.

The function of NMDA receptors varies according to the subregion of the hippocampus. NMDA receptors are required in the CA3 of the hippocampus when spatial information needs to be reorganized, while NMDA receptors in the CA1 are required in the acquisition and retrieval of memory after a delay, as well as in the formation of CA1 place fields. Blockade of the NMDA receptors prevents induction of long-term potentiation and impairs spatial learning.

The CA3 of the hippocampus plays an especially important role in the encoding and retrieval of spatial memories. The CA3 is innervated by two afferent paths known as the perforant path (PPCA3) and the dentate gyrus (DG)-mediated mossy fibers (MFs). The first path is regarded as the retrieval index path while the second is concerned with encoding.