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Brain Structure & Function Jul 2023The mammillary body (MB) is a component of the extended hippocampal system and many studies have shown that its functions are vital for mnemonic processes. Together with... (Review)
Review
The mammillary body (MB) is a component of the extended hippocampal system and many studies have shown that its functions are vital for mnemonic processes. Together with other subcortical structures, such as the anterior thalamic nuclei and tegmental nuclei of Gudden, the MB plays a crucial role in the processing of spatial and working memory, as well as navigation in rats. The aim of this paper is to review the distribution of various substances in the MB of the rat, with a description of their possible physiological roles. The following groups of substances are reviewed: (1) classical neurotransmitters (glutamate and other excitatory transmitters, gamma-aminobutyric acid, acetylcholine, serotonin, and dopamine), (2) neuropeptides (enkephalins, substance P, cocaine- and amphetamine-regulated transcript, neurotensin, neuropeptide Y, somatostatin, orexins, and galanin), and (3) other substances (calcium-binding proteins and calcium sensor proteins). This detailed description of the chemical parcellation may facilitate a better understanding of the MB functions and its complex relations with other structures of the extended hippocampal system.
Topics: Rats; Animals; Mammillary Bodies; Neurochemistry; Anterior Thalamic Nuclei; Amino Acids; Memory, Short-Term
PubMed: 37378855
DOI: 10.1007/s00429-023-02673-4 -
Mammillary body abnormalities and cognitive outcomes in children cooled for neonatal encephalopathy.Developmental Medicine and Child... Jun 2023To evaluate mammillary body abnormalities in school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal hypoxic-ischaemic...
AIM
To evaluate mammillary body abnormalities in school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (cases) and matched controls, and associations with cognitive outcome, hippocampal volume, and diffusivity in the mammillothalamic tract (MTT) and fornix.
METHOD
Mammillary body abnormalities were scored from T1-weighted magnetic resonance imaging (MRI) in 32 cases and 35 controls (median age [interquartile range] 7 years [6 years 7 months-7 years 7 months] and 7 years 4 months [6 years 7 months-7 years 7 months] respectively). Cognition was assessed using the Wechsler Intelligence Scale for Children, Fourth Edition. Hippocampal volume (normalized by total brain volume) was measured from T1-weighted MRI. Radial diffusivity and fractional anisotropy were measured in the MTT and fornix, from diffusion-weighted MRI using deterministic tractography.
RESULTS
More cases than controls had mammillary body abnormalities (34% vs 0%; p < 0.001). Cases with abnormal mammillary bodies had lower processing speed (p = 0.016) and full-scale IQ (p = 0.028) than cases without abnormal mammillary bodies, and lower scores than controls in all cognitive domains (p < 0.05). Cases with abnormal mammillary bodies had smaller hippocampi (left p = 0.016; right p = 0.004) and increased radial diffusivity in the right MTT (p = 0.004) compared with cases without mammillary body abnormalities.
INTERPRETATION
Cooled children with mammillary body abnormalities at school-age have reduced cognitive scores, smaller hippocampi, and altered MTT microstructure compared with those without mammillary body abnormalities, and matched controls.
WHAT THIS PAPER ADDS
Cooled children are at higher risk of mammillary body abnormalities than controls. Abnormal mammillary bodies are associated with reduced cognitive scores and smaller hippocampi. Abnormal mammillary bodies are associated with altered mammillothalamic tract diffusivity.
Topics: Infant, Newborn; Humans; Child; Infant; Mammillary Bodies; Fornix, Brain; Brain Diseases; Diffusion Magnetic Resonance Imaging; Cognition; Infant, Newborn, Diseases; Magnetic Resonance Imaging
PubMed: 36335569
DOI: 10.1111/dmcn.15453 -
Science Translational Medicine Apr 2023The neural circuits governing the induction and progression of neurodegeneration and memory impairment in Alzheimer's disease (AD) are incompletely understood. The...
The neural circuits governing the induction and progression of neurodegeneration and memory impairment in Alzheimer's disease (AD) are incompletely understood. The mammillary body (MB), a subcortical node of the medial limbic circuit, is one of the first brain regions to exhibit amyloid deposition in the 5xFAD mouse model of AD. Amyloid burden in the MB correlates with pathological diagnosis of AD in human postmortem brain tissue. Whether and how MB neuronal circuitry contributes to neurodegeneration and memory deficits in AD are unknown. Using 5xFAD mice and postmortem MB samples from individuals with varying degrees of AD pathology, we identified two neuronal cell types in the MB harboring distinct electrophysiological properties and long-range projections: lateral neurons and medial neurons. lateral MB neurons harbored aberrant hyperactivity and exhibited early neurodegeneration in 5xFAD mice compared with lateral MB neurons in wild-type littermates. Inducing hyperactivity in lateral MB neurons in wild-type mice impaired performance on memory tasks, whereas attenuating aberrant hyperactivity in lateral MB neurons ameliorated memory deficits in 5xFAD mice. Our findings suggest that neurodegeneration may be a result of genetically distinct, projection-specific cellular dysfunction and that dysregulated lateral MB neurons may be causally linked to memory deficits in AD.
Topics: Mice; Humans; Animals; Alzheimer Disease; Mammillary Bodies; Mice, Transgenic; Neurons; Brain; Memory Disorders; Disease Models, Animal; Amyloid beta-Peptides
PubMed: 37075128
DOI: 10.1126/scitranslmed.abq1019 -
Neuroscience and Biobehavioral Reviews Jul 2015It has long been assumed that the main function of the mammillary bodies is to provide a relay for indirect hippocampal inputs to the anterior thalamic nuclei. Such... (Review)
Review
It has long been assumed that the main function of the mammillary bodies is to provide a relay for indirect hippocampal inputs to the anterior thalamic nuclei. Such models afford the mammillary bodies no independent role in memory and overlook the importance of their other, non-hippocampal, inputs. This review focuses on recent advances that herald a new understanding of the importance of the mammillary bodies, and their inputs from the limbic midbrain, for anterior thalamic function. It has become apparent that the mammillary bodies' contribution to memory is not dependent on afferents from the subicular complex. Rather, the ventral tegmental nucleus of Gudden is a vital source of inputs that support memory processes within the medial mammillary bodies. In parallel, the lateral mammillary bodies, via their connections with the dorsal tegmental nucleus of Gudden, are critical for generating head-direction signals. These two parallel, but distinct, information streams converge on the anterior thalamic nuclei and support different aspects of spatial memory.
Topics: Animals; Anterior Thalamic Nuclei; Hippocampus; Humans; Mammillary Bodies; Memory; Spatial Memory
PubMed: 25107491
DOI: 10.1016/j.neubiorev.2014.07.025 -
Journal of Psychiatric Research Feb 2023We have previously reported an in vivo enlargement of the left hypothalamus in mood disorders using 7 T magnetic resonance imaging. The aim of this follow-up study was...
We have previously reported an in vivo enlargement of the left hypothalamus in mood disorders using 7 T magnetic resonance imaging. The aim of this follow-up study was to find out whether the hypothalamic volume difference may be located in the mammillary bodies (MB) rather than being widespread across the hypothalamus. We developed and evaluated a detailed segmentation algorithm that allowed a reliable segmentation of the MBs, and applied it to 20 unmedicated (MDDu) and 20 medicated patients with major depressive disorder, 21 medicated patients with bipolar disorder, and 23 controls. 20 out of 23 healthy controls were matched to the MDDu. We tested for group differences in MB and hypothalamus without MB (HTh) volumes using analyses of covariance. Associations between both volumes of interest were analysed using bivariate and partial correlations. In contrast to postmortem findings, we found no statistically significant differences of the MB volumes between the study groups. Left HTh volumes differed significantly across the study groups after correction for intracranial volume (ICV) and for ICV and sex. Our result of an HTh enlargement in mood disorders was confirmed by a paired t-test between the matched pairs of MDDu and healthy controls using the native MB and HTh volumes. In the whole sample, MB volumes correlated significantly with the ipsilateral HTh volumes. Our results indicate a structural relationship between both volumes, and that our previous in vivo finding of a hypothalamus enlargement does not extend to the MB, but is limited to the HTh. The enlargement is more likely related to the dysregulation of the HPA axis than to cognitive dysfunctions accompanying mood disorders.
Topics: Humans; Mood Disorders; Mammillary Bodies; Depressive Disorder, Major; Hypothalamo-Hypophyseal System; Follow-Up Studies; Pituitary-Adrenal System; Hypothalamus; Magnetic Resonance Imaging
PubMed: 36603316
DOI: 10.1016/j.jpsychires.2022.12.004 -
Translational Psychiatry Feb 2022Altered long-range connectivity is a common finding across neurodevelopmental psychiatric disorders, but causes and consequences are not well understood. Genetic...
Altered long-range connectivity is a common finding across neurodevelopmental psychiatric disorders, but causes and consequences are not well understood. Genetic variation in ST8SIA2 has been associated with schizophrenia, autism, and bipolar disorder, and St8sia2 mice show a number of related neurodevelopmental and behavioral phenotypes. In the present study, we use conditional knockout (cKO) to dissect neurodevelopmental defects and behavioral consequences of St8sia2 deficiency in cortical interneurons, their cortical environment, or in the di- and mesencephalon. Neither separate nor combined cortical and diencephalic ablation of St8sia2 caused the disturbed thalamus-cortex connectivity observed in St8sia2 mice. However, cortical ablation reproduced hypoplasia of corpus callosum and fornix and mice with di- and mesencephalic ablation displayed smaller mammillary bodies with a prominent loss of parvalbumin-positive projection neurons and size reductions of the mammillothalamic tract. In addition, the mammillotegmental tract and the mammillary peduncle, forming the reciprocal connections between mammillary bodies and Gudden's tegmental nuclei, as well as the size of Gudden's ventral tegmental nucleus were affected. Only mice with these mammillary deficits displayed enhanced MK-801-induced locomotor activity, exacerbated impairment of prepulse inhibition in response to apomorphine, and hypoanxiety in the elevated plus maze. We therefore propose that compromised mammillary body connectivity, independent from hippocampal input, leads to these psychotic-like responses of St8sia2-deficient mice.
Topics: Animals; Mammillary Bodies; Mesencephalon; Mice; Sialyltransferases; Tegmentum Mesencephali
PubMed: 35115485
DOI: 10.1038/s41398-022-01816-1 -
Scientific Reports Mar 2021The mammillary bodies (MB) and hippocampi are important for memory function and are often affected following neonatal hypoxic ischemic encephalopathy (HIE). The aim of... (Observational Study)
Observational Study
The mammillary bodies (MB) and hippocampi are important for memory function and are often affected following neonatal hypoxic ischemic encephalopathy (HIE). The aim of this study was to assess neurodevelopmental outcome in 10-year-old children with HIE with and without therapeutic hypothermia. Additional aims were to assess the associations between MB atrophy, brain volumes (including the hippocampi), white matter microstructure and neurodevelopmental outcome at school-age. Ten-year-old children with HIE were included, who were treated with therapeutic hypothermia (n = 22) or would have qualified but were born before this became standard of care (n = 28). Children completed a neuropsychological and motor assessment and MRI. Mammillary bodies were scored as normal or atrophic at 10 years. Brain volumes were segmented on childhood MRI and DTI scans were analysed using tract-based spatial statistics. Children with HIE suffered from neurocognitive and memory problems at school-age, irrespective of hypothermia. Hippocampal volumes and MB atrophy were associated with total and performance IQ, processing speed and episodic memory in both groups. Normal MB and larger hippocampi were positively associated with global fractional anisotropy. In conclusion, injury to the MB and hippocampi was associated with neurocognition and memory at school-age in HIE and might be an early biomarker for neurocognitive and memory problems.
Topics: Anisotropy; Atrophy; Child; Diffusion Tensor Imaging; Female; Hippocampus; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Male; Mammillary Bodies; Memory; Netherlands; Neuropsychological Tests; Psychomotor Performance; Retrospective Studies; Schools; Students; White Matter
PubMed: 33658541
DOI: 10.1038/s41598-021-83982-8 -
Journal of Neurosurgery May 2014
Topics: Cerebral Ventricle Neoplasms; Craniopharyngioma; Female; Humans; Male; Mammillary Bodies; Third Ventricle
PubMed: 24527817
DOI: 10.3171/2013.11.JNS132343 -
AJNR. American Journal of Neuroradiology Jun 2022Despite their small size, the mammillary bodies play an important role in supporting recollective memory. However, they have typically been overlooked when assessing... (Review)
Review
Despite their small size, the mammillary bodies play an important role in supporting recollective memory. However, they have typically been overlooked when assessing neurologic conditions that present with memory impairment. While there is increasing evidence of mammillary body involvement in a wide range of neurologic disorders in adults, very little attention has been given to infants and children. Literature searches of PubMed and EMBASE were performed to identify articles that describe mammillary body pathology on brain MR imaging in children. Mammillary body pathology is present in the pediatric population in several conditions, indicated by signal change and/or atrophy on MR imaging. The main causes of mammillary body pathology are thiamine deficiency, hypoxia-ischemia, direct damage due to masses or hydrocephalus, or deafferentation resulting from pathology within the wider Papez circuit. Optimizing scanning protocols and assessing mammillary body status as a standard procedure are critical, given their role in memory processes.
Topics: Adult; Atrophy; Child; Humans; Infant; Limbic System; Magnetic Resonance Imaging; Mammillary Bodies; Memory
PubMed: 35487586
DOI: 10.3174/ajnr.A7463 -
Progress in Brain Research 2015Although 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... (Review)
Review
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.
Topics: Animals; Hippocampus; Humans; Mammillary Bodies; Memory; Neural Pathways
PubMed: 26072239
DOI: 10.1016/bs.pbr.2015.03.006