Neuroanatomy, Mammillary Bodies


Article Author:
Diana Peterson


Article Editor:
Debra Mayes


Editors In Chief:
William Gossman


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
1/21/2019 9:33:31 AM

Introduction

The mammillary bodies are brainstem nuclei on the inferior and posterior aspect of the hypothalamus. There are 2 mammillary bodies on either side of the midline. Early anatomists named the structures after mammary tissue because they resembled small breasts (Figure 1A).[1]

Structure and Function

The mammillary bodies are one of the primary nuclei within the Papez Circuit (Figure 1B). The circuit assists with spatial and episodic memory consolidation and storage.[2][3] Therefore, damage to the fornix or mammillary bodies results in amnesia.[4][5] The mammillary bodies also function to assist with emotion and reward behaviors and goal-directed behaviors.[6][7] 

The primary function associated with the mammillary bodies is recollective memory. Memory information begins within the hippocampus. Theta waves activate CA3 neurons in the hippocampus. Information about memory transmits through the fornix to the mammillary bodies (orange line, Figure 1C). Mammillary bodies project to the anterior thalamic nuclei through the mammillothalamic tract. The anterior thalamic nuclei projects to the cingulate cortex, and the cingulate cortex to entorhinal cortex. There is then a bi-directional projection between the hippocampus and the entorhinal cortex that completes the circuit; the Papez circuit (Figure 1B). 

Beyond transmission of memory information, the mammillary bodies help facilitate the creation of appropriate behavioral reactions through reciprocal connections with the tegmentum (blue line, Figure 1C). The medial mammillary nucleus has bi-directional projections to the ventral tegmental area. The lateral mammillary nucleus has bi-directional connections to the dorsal tegmental nucleus. The ventral tegmentum is rich with dopamine neurons, and thus functions as a reward (pleasure) center of the brain. Memory information from the hippocampus combines with information about reward or aversive attributes about a specific stimulus or set of stimuli in the environment, which allows processing of the salience of environmental stimuli.[8] The mammillary bodies send information about reward or aversion through the anterior thalamic nucleus to the cingulate cortex where it assists with the creation of emotional perception.[9] 

The dorsal tegmental connections to the lateral mammillary nucleus functions to process goal-directed movement. The location of the dorsal tegmental nucleus is between the trochlear nuclei within the midbrain.[9] Neurons in the dorsal tegmental nucleus respond specifically to movement velocity, turning behaviors, and learned goal-directed behaviors.[10] It also has direct connections with the ventral tegmental nucleus. These connections help guide processing in the reward circuit to facilitate improved goal-directed behaviors.[10] The mammillary bodies connect this stream of information to the cerebellum.[6] Researchers hypothesize that this connection assists the cerebellum with its role in visuospatial orientation, movement learning, and motor memory.[6] If the hypothesis is correct, disruption of information flow between the cerebellum and mammillary bodies may contribute to navigational impairments during the early stages of neurodegenerative disorders.[11]

The mammillary bodies do not have interneurons. Processing of information within the mammillary bodies occurs from projection neurons of other regions of the brain. It receives both dopaminergic and acetylcholine reciprocal projections from the tegmentum (blue line, Figure 1C) that help to regulate what information the mammillary bodies send forward to the anterior thalamic nucleus (Papez circuit) and the cerebellum. Because tegmental connections are reciprocal (bi-directional), mammillary activity also influences the tegmentum and other connections of the tegmentum (e.g., amygdala, prefrontal cortex, hippocampus, and nucleus accumbens). Activation of the acetylcholine and dopamine circuits activate norepinephrine and serotonin systems downstream.[7] Each of these neurotransmitter systems helps to mediate memory storage within the cortex. They also help to facilitate other limbic functions (e.g., attention, learning, memory, motor systems, decision, planning, and emotion).[8][10]

Embryology

In development, the mammillary bodies form from the ectoderm layer. The ectoderm layer forms the neural tube that closes at six weeks of gestation. The neural tube differentiates into the forebrain, midbrain, hindbrain, and spinal cord. The forebrain section develops into the telencephalon and diencephalon. The hypothalamus, mammillary bodies, and posterior pituitary form from the diencephalon.[7][12]

Blood Supply and Lymphatics

Mammillary bodies receive blood supply from the circle of Willis, which runs on the inferior surface of the hypothalamus. Branches off the posteromedial artery directly supply the mammillary bodies. These arteries originate from the posterior cerebral artery but can originate off of the posterior communicating artery. The posteromedial artery has three branches: rostral, deep penetrating, and caudal. The caudal branches supply the mammillary bodies.[7]

Capillary plexus around the region carry blood away from the mammillary bodies through the hypothalamo-neurohypophysial portal system.[7] Blood moves from this portal system into the cavernous sinus. From the cavernous sinus, it travels through either the superior or inferior petrosal sinuses to enter the jugular vein. 

Lymphatics within the brain differ from other regions of the body. Within the brain, the blood-brain barrier regulates the movement/transport of nutrients, small molecules, metabolites, and/or cells and toxins in and out of the brain.  The blood-brain barrier is a functional and structural boundary between vasculature and the brain that forms from brain vasculature endothelial cells, adjacent astrocytic end-feet, and pericytes. Tight junctions connect brain endothelial cells and create a physical barrier. This barrier forces most molecules to travel through selective transcellular routes – forming a transport barrier. In addition, there is also a synergistic relationship between brain endothelial cells and astrocytes. Perivascular astrocytic end-feet surround brain endothelial cells, but a basal lamina separates them. The barrier formed from these astrocytic end-feet and endothelial cells protect the brain from toxins and assist with transport of nutrients, wastes, glucose, lipids, and neurotransmitters between capillaries and neurons in the brain. [7]

Nerves

Mammillary bodies have three large direct connection: hippocampus, thalamus, and tegmental nuclei (Figure 1C). The hippocampus projects to the mammillary bodies through afferent fibers in the fornix (orange line, Figure 1C). The mammillary bodies then process information about memory and then relay it up to the thalamus for additional processing through the mammillothalamic tract. This tract terminates within the anterior thalamic nuclei. (red line, Figure 1C). Both the hippocampal projections to the mammillary bodies as well as the projections from the mammillary bodies to the thalamus are uni-directional. These circuits are a part of the Papez circuit (Figure 1B).[7]

Mammillary bodies also have bi-directional connections with the tegmental nuclei through the mammillotegmental tract (blue line, Figure 1C). Because the tegmentum has numerous connections to several limbic structures, mammillary body input to this region can influence a variety of limbic functions (see above).[7]

Muscles

Although the mammillary bodies do not directly contact muscle, they have projections to the cerebellum, a secondary motor brain region. Mammillary inputs from the tegmentum carry information about movement velocity, turning behaviors, and learned goal-directed behaviors.[10][6] The mammillary bodies also receive information about memory from the hippocampus and stimulus salience from the tegmentum. Therefore, the mammillary bodies may also assist the cerebellum in its motor learning functions. 

Physiologic Variants

The mammillary bodies are a part of the hypothalamus. Physiology of this region of the brain is necessary for survival. Therefore, few developmental/physiological variations allow for the survival of a fetus.

Throughout life, the mammillary bodies adapt to environmental and physiological changes of an individual; this enables the individual to alter behavior based on learned salience of a stimulus or set of stimuli. Although it is ideal for the mammillary bodies to change with variations in environmental stimuli, the neurons, and connections with the mammillary bodies are susceptible to damage based on environmental factors (e.g., alcohol, thiamine deficiency).[9][13] These environmental factors, in addition to aging-related neurodegeneration, can dramatically influence the function of mammillary circuits.[14]

Surgical Considerations

The location of the mammillary bodies is one factor surgeons use as a guide in patients with craniopharyngiomas that involve the hypothalamus. In these patients, the location of the mammillary bodies move. Surgeons can measure the angle between the base of the mammillary bodies and the plane of the floor of the fourth ventricle in a midsagittal MRI as an indicator for the location of these types of tumors. Angles less than 60 degrees indicate a tuberal-interventricular tumor. Angles greater than 90 degrees show tumor invagination of the third ventricle. Thus mammillary body position is a quick reference for the location of these types of tumors. By understanding the location of the tumors, surgeons have more information on how to treat and manage these tumors.[15]

Clinical Significance

Damage to the mammillary bodies can occur through trauma, stroke, tumors, or environmental factors (e.g., thiamine deficiency or chronic alcoholism). Thiamine deficiency commonly causes Korsakoff's syndrome. This syndrome can occur with Wernicke encephalopathy, caused by chronic alcoholism because the alcoholism can induce a thiamine deficiency.[9][13] In both disorders, these environmental factors cause bilateral degeneration of the neurons or projections of the mammillary bodies.  Bilateral mammillary damage causes anterograde amnesia in patients. The memory loss can occur independently or can accompany a variety of other symptoms (e.g., reckless behavior, reduced motivation, confabulation).[16][9]

Other Issues

The mammillary bodies and circuits associated with the mammillary bodies (e.g., limbic structures) influence many higher-order functions. Researchers have hypothesized that stimulation of the Papez circuit may have beneficial effects on memory and attention as well as decreasing the incidence of depression in individuals with dementia. In animal models, deep brain stimulation of the hippocampus shows increased memory function with no signs of anxiety. Researchers attributed these results to increased activation of the cingulate gyrus through the hippocampus-mammillary tract, mammillothalamic tract, and thalamic projections to the cingulate gyrus (the brain location where emotion is perceived).[17]

Deep brain stimulation has been a treatment for Alzheimer disease, Parkinson disease, and dementia.[18][17][19][20][21] The location of the stimulation probe has shown optimal results when placed near the fornix to stimulate the hippocampal fibers projecting to the mammillary bodies.[20] These types of treatments have altered the rate of brain atrophy in Alzheimer patients.[22] How and why atrophy slows down by activation of the Papez circuit is unknown. However, these experiments show that deep brain stimulation of the Papez circuit may be a viable clinical treatment for individuals with a variety of psychiatric or dementia disorders.


  • Image 7380 Not availableImage 7380 Not available
    Created by Diana Peterson, Ph.D. for use with StatPearls.
Attributed To: Created by Diana Peterson, Ph.D. for use with StatPearls.

Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Neuroanatomy, Mammillary Bodies - Questions

Take a quiz of the questions on this article.

Take Quiz
Which of the following structures sends afferents to the mammillary body?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which thalamic nuclei receives input from the mammillary body?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
The mammillary bodies directly connect to what regions of the brain?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
The wife of a 45-year-old male referred him to his physician with complaints of gradual memory loss issues that was progressing over several months. His wife reported that the man has difficulty remembering recent events. Upon examination, the man repeats only 2 of 10 words in a 10-minute recollection test. One year prior, the man had a successful bariatric surgery. At the time of surgery, he weighed 300 pounds. At the time of his visit to the doctor's office, he weighed 150 pounds. Based on his history, what is the best diagnosis for the man's memory loss?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient comes to a clinic with his wife. The wife states that her husband has had no energy, is experiencing frequent mood swings, and is acting differently. She brought him in today because he is now having headaches with associated nausea. His Rhomberg test is positive and an MRI midsagittal section shows that the base of the mammillary bodies is at a 45-degree angle with the floor of the 4th ventricle. What diagnosis should be suspected?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the blood supply for the mammillary bodies?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A physician diagnoses a patient with the beginning stages of Alzheimer's disease. A treatment plan of deep brain stimulation to minimize the rate of brain deterioration is created. Where should the surgeon place the stimulator within the brain?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
How does modification of information within the mammillary bodies occur?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Deep brain stimulation has been utilized as a treatment for Alzheimer disease and dementia. When placing the stimulating electrode, what region of the brain is the target for optimal therapeutic effect?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Damage to the mammillary bodies may induce what symptoms or disorders?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Neuroanatomy, Mammillary Bodies - References

References

Bear MH,Bollu PC, Neuroanatomy, Hypothalamus null. 2018 Jan     [PubMed]
Qin C,Li J,Tang K, The Paraventricular Nucleus of the Hypothalamus: Development, Function, and Human Diseases. Endocrinology. 2018 Sep 1     [PubMed]
Cacciola A,Milardi D,Calamuneri A,Bonanno L,Marino S,Ciolli P,Russo M,Bruschetta D,Duca A,Trimarchi F,Quartarone A,Anastasi G, Constrained Spherical Deconvolution Tractography Reveals Cerebello-Mammillary Connections in Humans. Cerebellum (London, England). 2017 Apr     [PubMed]
Vann SD,Aggleton JP, The mammillary bodies: two memory systems in one? Nature reviews. Neuroscience. 2004 Jan     [PubMed]
Vertes RP,Albo Z,Viana Di Prisco G, Theta-rhythmically firing neurons in the anterior thalamus: implications for mnemonic functions of Papez's circuit. Neuroscience. 2001;     [PubMed]
Aggleton JP,Brown MW, Episodic memory, amnesia, and the hippocampal-anterior thalamic axis. The Behavioral and brain sciences. 1999 Jun;     [PubMed]
Thomas AG,Koumellis P,Dineen RA, The fornix in health and disease: an imaging review. Radiographics : a review publication of the Radiological Society of North America, Inc. 2011 Jul-Aug;     [PubMed]
Copenhaver BR,Rabin LA,Saykin AJ,Roth RM,Wishart HA,Flashman LA,Santulli RB,McHugh TL,Mamourian AC, The fornix and mammillary bodies in older adults with Alzheimer's disease, mild cognitive impairment, and cognitive complaints: a volumetric MRI study. Psychiatry research. 2006 Oct 30;     [PubMed]
Lammel S,Lim BK,Malenka RC, Reward and aversion in a heterogeneous midbrain dopamine system. Neuropharmacology. 2014 Jan;     [PubMed]
Balak N,Balkuv E,Karadag A,Basaran R,Biceroglu H,Erkan B,Tanriover N, Mammillothalamic and Mammillotegmental Tracts as New Targets for Dementia and Epilepsy Treatment. World neurosurgery. 2018 Feb;     [PubMed]
Redila V,Kinzel C,Jo YS,Puryear CB,Mizumori SJ, A role for the lateral dorsal tegmentum in memory and decision neural circuitry. Neurobiology of learning and memory. 2015 Jan;     [PubMed]
Levisohn L,Cronin-Golomb A,Schmahmann JD, Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population. Brain : a journal of neurology. 2000 May;     [PubMed]
Roberts DE,Killiany RJ,Rosene DL, Neuron numbers in the hypothalamus of the normal aging rhesus monkey: stability across the adult lifespan and between the sexes. The Journal of comparative neurology. 2012 Apr 15;     [PubMed]
Pascual JM,Prieto R,Carrasco R,Barrios L, Displacement of mammillary bodies by craniopharyngiomas involving the third ventricle: surgical-MRI correlation and use in topographical diagnosis. Journal of neurosurgery. 2013 Aug;     [PubMed]
Hescham S,Jahanshahi A,Meriaux C,Lim LW,Blokland A,Temel Y, Behavioral effects of deep brain stimulation of different areas of the Papez circuit on memory- and anxiety-related functions. Behavioural brain research. 2015 Oct 1;     [PubMed]
Sankar T,Chakravarty MM,Bescos A,Lara M,Obuchi T,Laxton AW,McAndrews MP,Tang-Wai DF,Workman CI,Smith GS,Lozano AM, Deep Brain Stimulation Influences Brain Structure in Alzheimer's Disease. Brain stimulation. 2015 May-Jun;     [PubMed]
Kril JJ,Harper CG, Neuroanatomy and neuropathology associated with Korsakoff's syndrome. Neuropsychology review. 2012 Jun;     [PubMed]
Hescham S,Lim LW,Jahanshahi A,Blokland A,Temel Y, Deep brain stimulation in dementia-related disorders. Neuroscience and biobehavioral reviews. 2013 Dec;     [PubMed]
Gratwicke J,Kahan J,Zrinzo L,Hariz M,Limousin P,Foltynie T,Jahanshahi M, The nucleus basalis of Meynert: a new target for deep brain stimulation in dementia? Neuroscience and biobehavioral reviews. 2013 Dec;     [PubMed]
Stypulkowski PH,Stanslaski SR,Giftakis JE, Modulation of hippocampal activity with fornix Deep Brain Stimulation. Brain stimulation. 2017 Nov - Dec;     [PubMed]
Zhang C,Hu WH,Wu DL,Zhang K,Zhang JG, Behavioral effects of deep brain stimulation of the anterior nucleus of thalamus, entorhinal cortex and fornix in a rat model of Alzheimer's disease. Chinese medical journal. 2015 May 5;     [PubMed]
Dusoir H,Kapur N,Byrnes DP,McKinstry S,Hoare RD, The role of diencephalic pathology in human memory disorder. Evidence from a penetrating paranasal brain injury. Brain : a journal of neurology. 1990 Dec;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Adult Ambulatory-Medical Student. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Adult Ambulatory-Medical Student, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Adult Ambulatory-Medical Student, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Adult Ambulatory-Medical Student. When it is time for the Adult Ambulatory-Medical Student board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Adult Ambulatory-Medical Student.