It has long been supposed that the mammillary bodies contribute to learning and memory, although the importance of these nuclei and the nature of their contributions have remained poorly understood. Recent electrophysiological data, combined with an appreciation of the anatomical connections of this region, provide a new framework within which to examine this diencephalic region.
The mammillary bodies can be divided on cytoarchitectonic and connectional grounds into a lateral and a medial division. The lateral and medial mammillary nuclei are connected with the same regions (anterior thalamic nuclei, Gudden's tegmental nuclei, the hippocampal formation), but with different subfields or nuclei within these regions. This pattern suggests the presence of two parallel systems, which might have different functions but nevertheless contribute to the same classes of learning.
The lateral mammillary nucleus contains head direction cells that signal the horizontal orientation of an animal. The activity of these cells is necessary for the anterior thalamic head direction signal, which is in turn crucial for head direction signals in the hippocampal formation. The medial mammillary nucleus contains theta-related cells that are thought to reflect hippocampal activity, and are assumed to relay to the anterior thalamic nuclei. Theta is assumed to act as a 'significance signal', so that information arriving with theta activity is more likely to be stored.
The effects of selective mammillary body lesions in animals consistently point to the involvement of this region in the encoding of spatial information. It is argued that the medial and lateral nuclei contribute in different ways so that they complement each other. Although this assumption remains to be tested directly, it is known that the effects of selective lesions in the anterior thalamic nuclei, to which the mammillary bodies project, are additive. These data support the notion of two distinct, but related, functions.
Clinical studies into the effects of mammillary body damage indicate that this region is necessary for the normal recall of episodic information. This conclusion is reinforced by recent studies revealing the importance for memory of the mammillothalamic tract, the main output route from the mammillary bodies. The severity of the memory loss associated with mammillary body damage depends upon the extent of damage to other diencephalic regions, key amongst these being the anterior thalamic nuclei.
It is proposed that the mammillary bodies permit the integration of orientation information and theta, so enable the storing of scene information. These twin roles aid episodic recall.
Although the mammillary bodies have been implicated in amnesia perhaps for longer than any other single brain region, their role has remained elusive. It is now emerging that the difficulties in understanding the importance of the mammillary bodies for memory might stem from the tradition of treating the mammillary bodies as a single structure with a single function. This review will dissect the mammillary bodies and show how their component nuclei might have multiple functions that, nevertheless, are coordinated to give the impression of a unitary function.
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The authors declare no competing financial interests.
- EPISODIC MEMORY
The recollection of events in an autobiographical context.
- THETA RHYTHM
Rhythmic neural activity with a frequency of 4–8 Hz.
- MORRIS WATER MAZE
A learning task in which an animal is placed in a pool filled with opaque water and has to learn to escape to a hidden platform that is placed at a constant position. The animal must learn to use distal cues, and the spatial relationship between them and the platform. Learning in this task involves the hippocampus.
Distal cues that provide geometric reference to current location.
- LONG-TERM POTENTIATION
(LTP). An enduring increase in the amplitude of excitatory postsynaptic potentials as a result of high-frequency (tetanic) stimulation of afferent pathways. It is measured both as the amplitude of excitatory postsynaptic potentials and as the magnitude of the postsynaptic cell population spike. LTP is most often studied in the hippocampus and is often considered to be the cellular basis of learning and memory in vertebrates.
- DIENCEPHALIC ANTEROGRADE AMNESIA
Impaired learning of new declarative information following pathology in the medial thalamic or hypothalamic regions.
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Vann, S., Aggleton, J. The mammillary bodies: two memory systems in one?. Nat Rev Neurosci 5, 35–44 (2004). https://doi.org/10.1038/nrn1299
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