The mammillary bodies and memory: more than a hippocampal relay

doi:10.1016/bs.pbr.2015.03.006

Progress in Brain Research

Volume 219, 2015, Pages 163-185

https://doi.org/10.1016/bs.pbr.2015.03.006 Get rights and content

Abstract

Although the mammillary bodies were one of the first neural structures to be implicated in memory, it has long been assumed that their main function was to act primarily as a hippocampal relay, passing information on to the anterior thalamic nuclei and from there to the cingulate cortex. This view not only afforded the mammillary bodies no independent role in memory, it also neglected the potential significance of other, nonhippocampal, inputs to the mammillary bodies. Recent advances have transformed the picture, revealing that projections from the tegmental nuclei of Gudden, and not the hippocampal formation, are critical for sustaining mammillary body function. By uncovering a role for the mammillary bodies that is independent of its subicular inputs, this work signals the need to consider a wider network of structures that form the neural bases of episodic memory.

Introduction

The hippocampal-mammillary body projections hold a noteworthy position in history; they were the arguably the first hippocampal projections to undergo experimental analysis and, until the mid-twentieth century, were the principal focus of attention in terms of hippocampal outputs (Gudden, 1881, MacLean, 1990). Both the medial temporal lobe and medial diencephalon, comprising the hippocampus and mammillary bodies, respectively, have been implicated in event memory for over a hundred years, but there remains much uncertainty about how these brain regions interact to support this function. Since Papez proposed his model of emotion in 1937, most accounts of mammillary body function have emphasized the importance of hippocampal inputs to this region, effectively relegating the mammillary bodies to the status of a relay within an “extended hippocampal system” (Aggleton and Brown, 1999, Papez, 1937). However, recent advances in our understanding challenge the prevalent hippocampal-centric view of mammillary body function. In contrast to traditional models, it appears that independent ascending projections from the mammillary bodies are key for some aspects of hippocampal function.

Section snippets

The Papez Circuit: Anatomy

In his proposed mechanism of emotion, Papez described a circuit that originated in the cortex, then “built up in the hippocampal formation and…transferred to the mammillary body and thence through the anterior thalamic nuclei to the cortex of the gyrus cinguli” (Papez, 1937, p. 728). In terms of hippocampal outputs, the projections to the mammillary bodies were seen as key. The mammillary bodies are remarkable for a number of reasons. They are clearly discernable as two spherical structures on

The Papez Circuit: Function

While we now know that structures within the Papez circuit are important for memory, it was not until the mid-twentieth century that this view became widely accepted. Up to this point, the hippocampus had been linked to a number of different functions including sensation, olfaction, and attention. Papez originally made the link with emotion as a result of his work on the rabies virus. The rabies virus principally affects the hippocampus, and Papez, therefore, attributed the emotive changes seen

Medial Diencephalic-Temporal Lobe Interactions

Traditional models emphasize the hippocampal inputs to the mammillary bodies within an extended memory system emanating from the hippocampus. If the mammillary bodies are more than a hippocampal relay and make a contribution to memory that is dependent on their inputs from the limbic midbrain rather than the hippocampus (Dillingham et al., 2014, Vann, 2013, Vann et al., 2011), then these models require revision. Evidence from cross-lesions studies would suggest that the hippocampus and anterior

Conclusions

Ever since Papez proposed his influential circuit, the mammillary bodies have been viewed principally in terms of their hippocampal inputs. However, for both the medial and lateral mammillary bodies, their ascending inputs from the tegmental nuclei appear to be, functionally, more important than those from the hippocampal formation (e.g., Dillingham et al., 2014, Goodridge and Taube, 1997, Stackman and Taube, 1997, Taube et al., 1996, Tonkiss and Rawlins, 1992, Vann, 2013). These findings are

Acknowledgments

S.D.V. is funded by a Wellcome Trust Senior Research Fellowship in Basic Biomedical Science (Grant number WT090954AIA). Thanks to Lorraine Woods for help with illustrations and John Aggleton for helpful discussion.

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Extracting the valence of environmental cues is critical for animals’ survival. How valence in sensory signals is encoded and transformed to produce distinct behavioral responses remains not well understood. Here, we report that the mouse pontine central gray (PCG) contributes to encoding both negative and positive valences. PCG glutamatergic neurons were activated selectively by aversive, but not reward, stimuli, whereas its GABAergic neurons were preferentially activated by reward signals. The optogenetic activation of these two populations resulted in avoidance and preference behavior, respectively, and was sufficient to induce conditioned place aversion/preference. Suppression of them reduced sensory-induced aversive and appetitive behaviors, respectively. These two functionally opponent populations, receiving a broad range of inputs from overlapping yet distinct sources, broadcast valence-specific information to a distributed brain network with distinguishable downstream effectors. Thus, PCG serves as a critical hub to process positive and negative valences of incoming sensory signals and drive valence-specific behaviors with distinct circuits.
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A key to goal-oriented engram processing lies in the motivation-biased base of the brain. The hypothalamus is a surprisingly important node in mnemonic loops [22]. At only 2% of brain volume in rodents (0.3% volume in humans) [23,24], it is nonetheless key to a vast range of functions.
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Mammillary body and their projections to the anterior thalamus via the mammillothalamic tract are important for recollection memory. It plays an important role in spatial and episodic memory (22). Similarly, fornix is an important structure in limbic system forming the hippocampal-diencephalic-cingulate network.
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Chapter 9 - The mammillary bodies and memory: more than a hippocampal relay

Abstract

Introduction

Section snippets

The Papez Circuit: Anatomy

The Papez Circuit: Function

Medial Diencephalic-Temporal Lobe Interactions

Conclusions

Acknowledgments

Behav. Brain Res.

Behav. Brain Res.

Behav. Brain Res.

Neuropsychologia

Neuropsychologia

Prog. Neurobiol.

Neurobiol. Learn. Mem.

Brain Lang.

Brain Lang.

Brain Res.

Neuroscience

Brain Res.

Neuroscience

Neuropsychologia

Cortex

Neuropsychologia

Neuropsychologia

Neuropsychologia

Neuropsychologia

Exp. Neurol.

Behav. Brain Res.

Neurobiol. Learn. Mem.

Neuropsychologia

Cortex

Cortex

Cortex

EPS Mid-Career Award 2006. Understanding anterograde amnesia: disconnections and hidden lesions

Q. J. Exp. Psychol. (Hove)

Episodic memory, amnesia, and the hippocampal-anterior thalamic axis

Behav. Brain Sci.

A comparison of the effects of medial prefrontal, cingulate cortex, and cingulum bundle lesions on tests of spatial memory: evidence of a double dissociation between frontal and cingulum bundle contributions

J. Neurosci.

Differential cognitive effects of colloid cysts in the third ventricle that spare or compromise the fornix

Brain

Projections from the hippocampal region to the mammillary bodies in macaque monkeys

Eur. J. Neurosci.

Mamillary body in the rat: topography and synaptology of projections from the subicular complex, prefrontal cortex, and midbrain tegmentum

J. Comp. Neurol.

Defect of memorizing of hippocampal-mammillary origin: a review

J. Neurol. Neurosurg. Psychiatry

Human Memory and Its Pathology

Neural correlates for angular head velocity in the rat dorsal tegmental nucleus

J. Neurosci.

Lesions of the tegmentomammillary circuit in the head direction system disrupt the head direction signal in the anterior thalamus

J. Neurosci.

Demonstration eines Gehirns mit Zerstörung der vorderen und inneren Teile der Hirnrinde beider Schläfenlappen

Neurol. Zentralbl.

Uber das anomische substrat des Korsakowschen Syndromes

Schweizerisches Arch. Psychiatr. Nervenkr.

Strongly reduced number of parvalbumin-immunoreactive projection neurons in the mammillary bodies in schizophrenia: further evidence for limbic neuropathology

Ann. N.Y. Acad. Sci.

The anterior thalamic head-direction signal is abolished by bilateral but not unilateral lesions of the lateral mammillary nucleus

J. Neurosci.

An investigation into the functions of the occipital and temporal lobes of the monkey's brain

Philos. Trans. R. Soc. Lond. B

Alcoholic Korsakoff's Syndrome: An Information-Processing Approach to Amnesia

Both anteromedial and anteroventral thalamic lesions impair radial-maze learning in rats

Behav. Neurosci.

Again the James-Lange and the thalamic theories of emotion

Psychol. Rev.

Functional MRI study of diencephalic amnesia in Wernicke-Korsakoff syndrome

Brain

The Hypothalamus: Morphological, Functional, Clinical and Surgical Aspects

Pure amnesia after unilateral left polar thalamic infarct: topographic and sequential neuropsychological and metabolic (PET) correlations

J. Neurol. Neurosurg. Psychiatry

Le Syndrome de Korsakoff

How do mammillary body inputs contribute to anterior thalamic function?

Neurosci. Biobehav. Rev.

Fornical and non-fornical projections from the rat hippocampal formation to the anterior thalamic nuclei

Hippocampus