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Molecular Psychiatry Sep 2019Sleep and wakefulness control in the mammalian brain requires the coordination of various discrete interconnected neurons. According to the most conventional sleep... (Review)
Review
Sleep and wakefulness control in the mammalian brain requires the coordination of various discrete interconnected neurons. According to the most conventional sleep model, wake-promoting neurons (WPNs) and sleep-promoting neurons (SPNs) compete for network dominance, creating a systematic "switch" that results in either the sleep or awake state. WPNs and SPNs are ubiquitous in the brainstem and diencephalon, areas that together contain <1% of the neurons in the human brain. Interestingly, many of these WPNs and SPNs co-express and co-release various types of the neurotransmitters that often have opposing modulatory effects on the network. Co-transmission is often beneficial to structures with limited numbers of neurons because it provides increasing computational capability and flexibility. Moreover, co-transmission allows subcortical structures to bi-directionally control postsynaptic neurons, thus helping to orchestrate several complex physiological functions such as sleep. Here, we present an in-depth review of co-transmission in hypothalamic WPNs and SPNs and discuss its functional significance in the sleep-wake network.
Topics: Animals; Brain; Brain Stem; Diencephalon; Humans; Hypothalamus; Nerve Net; Neurons; Neurotransmitter Agents; Sleep; Wakefulness
PubMed: 30377299
DOI: 10.1038/s41380-018-0291-2 -
Brain Structure & Function Sep 2023The Subthalamic Nucleus (STh) is a lens-shaped subcortical structure located ventrally to the thalamus, that despite being embryologically derived from the diencephalon,... (Review)
Review
The Subthalamic Nucleus (STh) is a lens-shaped subcortical structure located ventrally to the thalamus, that despite being embryologically derived from the diencephalon, is functionally implicated in the basal ganglia circuits. Because of this strict structural and functional relationship with the circuits of the basal ganglia, the STh is a current target for deep brain stimulation, a neurosurgical procedure employed to alleviate symptoms in movement disorders, such as Parkinson's disease and dystonia. However, despite the great relevance of this structure for both basal ganglia physiology and pathology, the neurochemical and molecular anatomy of the STh remains largely unknown. Few studies have specifically addressed the detection of neurotransmitter systems and their receptors within the structure, and even fewer have investigated their topographical distribution. Here, we have reviewed the scientific literature on neurotransmitters relevant in the STh function of rodents, non-human primates and humans including glutamate, GABA, dopamine, serotonin, noradrenaline with particular focus on their subcellular, cellular and topographical distribution. Inter-species differences were highlighted to provide a framework for further research priorities, particularly in humans.
Topics: Animals; Humans; Subthalamic Nucleus; Basal Ganglia; Thalamus; Dopamine; Parkinson Disease
PubMed: 37479801
DOI: 10.1007/s00429-023-02678-z -
Neuroscience and Biobehavioral Reviews Feb 2021The medial diencephalon, in particular the mammillary bodies and anterior thalamic nuclei, has long been linked to memory and amnesia. The mammillary bodies provide a... (Review)
Review
The medial diencephalon, in particular the mammillary bodies and anterior thalamic nuclei, has long been linked to memory and amnesia. The mammillary bodies provide a dense input into the anterior thalamic nuclei, via the mammillothalamic tract. In both animal models, and in patients, lesions of the mammillary bodies, mammillothalamic tract and anterior thalamic nuclei all produce severe impairments in temporal and contextual memory, yet it is uncertain why these regions are critical. Mounting evidence from electrophysiological and neural imaging studies suggests that mammillothalamic projections exercise considerable distal influence over thalamo-cortical and hippocampo-cortical interactions. Here, we outline how damage to the mammillary body-anterior thalamic axis, in both patients and animal models, disrupts behavioural performance on tasks that relate to contextual ("where") and temporal ("when") processing. Focusing on the medial mammillary nuclei as a possible 'theta-generator' (through their interconnections with the ventral tegmental nucleus of Gudden) we discuss how the mammillary body-anterior thalamic pathway may contribute to the mechanisms via which the hippocampus and neocortex encode representations of experience.
Topics: Amnesia; Animals; Anterior Thalamic Nuclei; Humans; Mammillary Bodies; Memory; Neural Pathways
PubMed: 33309908
DOI: 10.1016/j.neubiorev.2020.11.031 -
Journal of Molecular Endocrinology Apr 2015Significant progress has been made recently in unravelling the embryonic events leading to pituitary morphogenesis, both in vivo and in vitro. This includes dissection... (Review)
Review
Significant progress has been made recently in unravelling the embryonic events leading to pituitary morphogenesis, both in vivo and in vitro. This includes dissection of the molecular mechanisms controlling patterning of the ventral diencephalon that regulate formation of the pituitary anlagen or Rathke's pouch. There is also a better characterisation of processes that underlie maintenance of pituitary progenitors, specification of endocrine lineages and the three-dimensional organisation of newly differentiated endocrine cells. Furthermore, a population of adult pituitary stem cells (SCs), originating from embryonic progenitors, have been described and shown to have not only regenerative potential, but also the capacity to induce tumour formation. Finally, the successful recapitulation in vitro of embryonic events leading to generation of endocrine cells from embryonic SCs, and their subsequent transplantation, represents exciting advances towards the use of regenerative medicine to treat endocrine deficits. In this review, an up-to-date description of pituitary morphogenesis will be provided and discussed with particular reference to pituitary SC studies.
Topics: Animals; Gene Expression Regulation, Developmental; Mice; Models, Biological; Morphogenesis; Pituitary Gland; Stem Cells
PubMed: 25587054
DOI: 10.1530/JME-14-0237 -
European Neurology 2007
Topics: Humans; Thalamic Nuclei; Thalamus
PubMed: 17218772
DOI: 10.1159/000098475 -
Journal of Anatomy 2001The epithalamus is a major subdivision of the diencephalon constituted by the habenular nuclei and pineal complex. Structural asymmetries in this region are widespread... (Review)
Review
The epithalamus is a major subdivision of the diencephalon constituted by the habenular nuclei and pineal complex. Structural asymmetries in this region are widespread amongst vertebrates and involve differences in size. neuronal organisation, neurochemistry and connectivity. In species that possess a photoreceptive parapineal organ, this structure projects asymmetrically to the left habenula, and in teleosts it is also situated on the left side of the brain. Asymmetries in size between the left and right sides of the habenula are often associated with asymmetries in neuronal organisation, although these two types of asymmetry follow different evolutionary courses. While the former is more conspicuous in fishes (with the exception of teleosts), asymmetries in neuronal organisation are more robust in amphibia and reptiles. Connectivity of the parapineal organ with the left habenula is not always coupled with asymmetries in habenular size and/or neuronal organisation suggesting that, at least in some species, assignment of parapineal and habenular asymmetries may be independent events. The evolutionary origins of epithalamic structures are uncertain but asymmetry in this region is likely to have existed at the origin of the vertebrate, perhaps even the chordate, lineage. In at least some extant vertebrate species, epithalamic asymmetries are established early in development, suggesting a genetic regulation of asymmetry. In some cases, epigenetic factors such as hormones also influence the development of sexually dimorphic habenular asymmetries. Although the genetic and developmental mechanisms by which neuroanatomical asymmetries are established remain obscure, some clues regarding the mechanisms underlying laterality decisions have recently come from studies in zebrafish. The Nodal signalling pathway regulates laterality by biasing an otherwise stochastic laterality decision to the left side of the epithalamus. This genetic mechanism ensures a consistency of epithalamic laterality within the population. Between species, the laterality of asymmetry is variable and a clear evolutionary picture is missing. We propose that epithalamic structural asymmetries per se and not the laterality of these asymmetries are important for the behaviour of individuals within a species. A consistency of the laterality within a population may play a role in social behaviours between individuals of the species.
Topics: Amphibians; Animals; Biological Evolution; Epithalamus; Fishes; Functional Laterality; Habenula; Hormones; Pineal Gland; Reptiles; Species Specificity; Vertebrates
PubMed: 11523830
DOI: 10.1046/j.1469-7580.2001.19910063.x -
Molecular Brain Jan 2021The hypothalamus links the nervous system to the endocrine system and plays a crucial role in maintaining the human body's homeostasis. This study aims to investigate...
The hypothalamus links the nervous system to the endocrine system and plays a crucial role in maintaining the human body's homeostasis. This study aims to investigate the resting state functional connectivity (rsFC) changes of the hypothalamus in fibromyalgia patients. 24 Fibromyalgia patients and 24 matched healthy controls (HCs) were recruited. Resting state fMRI data were collected from the fibromyalgia patients and HC's. Fibromyalgia patients went through a second scan after 12 weeks of Tai Chi mind-body intervention. Data analysis showed that fibromyalgia patients displayed less medial hypothalamus (MH) rsFC with the thalamus and amygdala when compared to the functional connectivity in the HCs. After the Tai Chi mind-body intervention, fibromyalgia patients showed increased MH rsFC with the thalamus and amygdala accompanied by clinical improvement. Effective connectivity analysis showed disrupted MH and thalamus interaction in the fibromyalgia patients, which was altered by mind-body exercise. Our findings suggest that fibromyalgia is associated with altered functional connectivity within the diencephalon and limbic system. Elucidating the roles of the diencephalon and limbic system in the pathophysiology and development of fibromyalgia may facilitate the development of a new biomarker and effective treatment methods for this prevalent disorder.Trial Registration ClinicalTrials.gov, NCT02407665. Registered: 3 April 2015, https://clinicaltrials.gov/ct2/show/NCT02407665?term=NCT02407665&draw=2&rank=1.
Topics: Female; Fibromyalgia; Humans; Hypothalamus; Limbic System; Male; Middle Aged; Nerve Net; Rest; Thalamus
PubMed: 33472674
DOI: 10.1186/s13041-020-00705-2 -
Developmental Biology Feb 2021Nodal signaling is essential for mesoderm and endoderm formation, as well as neural plate induction and establishment of left-right asymmetry. However, the mechanisms...
Nodal signaling is essential for mesoderm and endoderm formation, as well as neural plate induction and establishment of left-right asymmetry. However, the mechanisms controlling expression of Nodal pathway genes in these contexts are not fully known. Previously, we showed that Cdx1b induces expression of downstream Nodal signaling factors during early endoderm formation. In this study, we show that Cdx1b also regulates epithalamic asymmetry in zebrafish embryos by modulating expression of ndr2 and lft1. We first knocked down cdx1b with translation-blocking and splicing-blocking morpholinos (MOs). Most embryos injected with translation-blocking MOs showed absent ndr2, lft1 and pitx2c expression in the left dorsal diencephalon during segmentation and pharyngula stages accompanied by aberrant parapineal migration and habenular laterality at 72 h post fertilization (hpf). These defects were less frequent in embryos injected with splicing-blocking MO. To confirm the morphant phenotype, we next generated both zygotic (Z)cdx1b and maternal zygotic (MZ)cdx1b mutants by CRISPR-Cas9 mutagenesis. Expression of ndr2, lft1 and pitx2c was absent in the left dorsal diencephalon of a high proportion of MZcdx1b mutants; however, aberrant dorsal diencephalic pitx2c expression patterns were observed at low frequency in Zcdx1b mutant embryos. Correspondingly, dysregulated parapineal migration and habenular laterality were also observed in MZcdx1b mutant embryos at 72 hpf. On the other hand, Kupffer's vesicle cilia length and number, expression pattern of spaw in the lateral plate mesoderm and pitx2c in the gut as well as left-right patterning of various visceral organs were not altered in MZcdx1b mutants compared to wild-type embryos. Chromatin immunoprecipitation revealed that Cdx1b directly regulates ndr2 and lft1 expression. Furthermore, injection of cdx1b-vivo MO1 but not cdx1b-vivo 4 mm MO1 in the forebrain ventricle at 18 hpf significantly downregulated lft1 expression in the left dorsal diencephalon at 23-24 s stages. Together, our results suggest that Cdx1b regulates transcription of ndr2 and lft1 to maintain proper Nodal activity in the dorsal diencephalon and epithalamic asymmetry in zebrafish embryos.
Topics: Animals; Body Patterning; Cell Movement; Diencephalon; Embryo, Nonmammalian; Epithalamus; Gene Expression Profiling; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; Habenula; Heart; Homeodomain Proteins; Intracellular Signaling Peptides and Proteins; Left-Right Determination Factors; Nodal Protein; Pineal Gland; Protein Binding; Signal Transduction; Zebrafish; Zebrafish Proteins
PubMed: 33197427
DOI: 10.1016/j.ydbio.2020.11.001 -
Neuropsychology Review Sep 2021The thalamus, a significant part of the diencephalon, is a symmetrical and bilateral central brain structure. The thalamus is subdivided into three major groups of... (Review)
Review
The thalamus, a significant part of the diencephalon, is a symmetrical and bilateral central brain structure. The thalamus is subdivided into three major groups of nuclei based on their function: sensorimotor nuclei (or principal/relay nuclei), limbic nuclei and nuclei bridging these two domains. Anatomically, nuclei within the thalamus are described by their location, such as anterior, medial, lateral, ventral, and posterior. In this review, we summarize the role of medial and midline thalamus in cognition, ranging from learning and memory to flexible adaptation. We focus on the discoveries in animal models of alcohol-related brain damage, which identify the loss of neurons in the medial and midline thalamus as drivers of cognitive dysfunction associated with alcohol use disorders. Models of developmental ethanol exposure and models of adult alcohol-related brain damage and are compared and contrasted, and it was revealed that there are similar (anterior thalamus) and different (intralaminar [adult exposure] versus ventral midline [developmental exposure]) thalamic pathology, as well as disruptions of thalamo-hippocampal and thalamo-cortical circuits. The final part of the review summarizes approaches to recover alcohol-related brain damage and cognitive and behavioral outcomes. These approaches include pharmacological, nutritional and behavioral interventions that demonstrated the potential to mitigate alcohol-related damage. In summary, the medial/midline thalamus is a significant contributor to cognition function, which is also sensitive to alcohol-related brain damage across the life span, and plays a role in alcohol-related cognitive dysfunction.
Topics: Alcoholism; Animals; Brain; Humans; Neural Pathways; Thalamus
PubMed: 32789537
DOI: 10.1007/s11065-020-09450-8 -
TheScientificWorldJournal 2013Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome... (Review)
Review
Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans.
Topics: Acetylcholinesterase; Animals; Choline O-Acetyltransferase; Diencephalon; Down-Regulation; Hippocampus; Humans; Korsakoff Syndrome; Receptors, Cholinergic; Thiamine Deficiency; Wernicke Encephalopathy
PubMed: 24235882
DOI: 10.1155/2013/309143