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Frontiers in Endocrinology 2023AXL is a receptor tyrosine kinase commonly associated with a variety of human cancers. Along with its ligand Gas6 (growth arrest-specific protein 6), AXL is emerging as... (Review)
Review
AXL is a receptor tyrosine kinase commonly associated with a variety of human cancers. Along with its ligand Gas6 (growth arrest-specific protein 6), AXL is emerging as an important regulator of neuroendocrine development and function. AXL signaling in response to Gas6 binding impacts neuroendocrine structure and function at the level of the brain, pituitary, and gonads. During development, AXL has been identified as an upstream inhibitor of gonadotropin receptor hormone (GnRH) production and also plays a key role in the migration of GnRH neurons from the olfactory placode to the forebrain. AXL is implicated in reproductive diseases including some forms of idiopathic hypogonadotropic hypogonadism and evidence suggests that AXL is required for normal spermatogenesis. Here, we highlight research describing AXL/Gas6 signaling mechanisms with a focus on the molecular pathways related to neuroendocrine function in health and disease. In doing so, we aim to present a concise account of known AXL/Gas6 signaling mechanisms to identify current knowledge gaps and inspire future research.
Topics: Humans; Male; Axl Receptor Tyrosine Kinase; Gonadotropin-Releasing Hormone; Hypothalamic-Pituitary-Gonadal Axis; Prosencephalon; Proto-Oncogene Proteins
PubMed: 37396176
DOI: 10.3389/fendo.2023.1212104 -
Anatomical Science International Jun 2021Neuronal circuits in the neocortex and hippocampus are essential for higher brain functions such as motor learning and spatial memory. In the mammalian forebrain, most... (Review)
Review
Neuronal circuits in the neocortex and hippocampus are essential for higher brain functions such as motor learning and spatial memory. In the mammalian forebrain, most excitatory synapses of pyramidal neurons are formed on spines, which are tiny protrusions extending from the dendritic shaft. The spine contains specialized molecular machinery that regulates synaptic transmission and plasticity. Spine size correlates with the efficacy of synaptic transmission, and spine morphology affects signal transduction at the post-synaptic compartment. Plasticity-related changes in the structural and molecular organization of spine synapses are thought to underlie the cellular basis of learning and memory. Recent advances in super-resolution microscopy have revealed the molecular mechanisms of the nanoscale synaptic structures regulating synaptic transmission and plasticity in living neurons, which are difficult to investigate using electron microscopy alone. In this review, we summarize recent advances in super-resolution imaging of spine synapses and discuss the implications of nanoscale structures in the regulation of synaptic function, learning, and memory.
Topics: Animals; Dendritic Spines; Humans; Microscopy; Neuronal Plasticity; Neurons; Prosencephalon; Synapses; Synaptic Transmission
PubMed: 33459976
DOI: 10.1007/s12565-021-00603-0 -
Journal of Neuroscience Research Mar 2017Cholinergic activation regulates cognitive function, particularly long-term memory consolidation. This Review presents an overview of the anatomical, neurochemical, and... (Review)
Review
Cholinergic activation regulates cognitive function, particularly long-term memory consolidation. This Review presents an overview of the anatomical, neurochemical, and pharmacological evidence supporting the cholinergic regulation of Pavlovian contextual and cue-conditioned fear learning and extinction. Basal forebrain cholinergic neurons provide inputs to neocortical regions and subcortical limbic structures such as the hippocampus and amygdala. Pharmacological manipulations of muscarinic and nicotinic receptors support the role of cholinergic processes in the amygdala, hippocampus, and prefrontal cortex in modulating the learning and extinction of contexts or cues associated with threat. Additional evidence from lesion studies and analysis of in vivo acetylcholine release with microdialysis similarly support a critical role of cholinergic neurotransmission in corticoamygdalar or corticohippocampal circuits during acquisition of fear extinction. Although a few studies have suggested a complex role of cholinergic neurotransmission in the cellular plasticity essential for extinction learning, more work is required to elucidate the exact cholinergic mechanisms and physiological role of muscarinic and nicotinic receptors in these fear circuits. Such studies are important for elucidating the role of cholinergic neurotransmission in disorders such as posttraumatic stress disorder that involve deficits in extinction learning as well as for developing novel therapeutic approaches for such disorders. © 2016 Wiley Periodicals, Inc.
Topics: Acetylcholine; Animals; Extinction, Psychological; Fear; Humans; Learning; Prosencephalon
PubMed: 27704595
DOI: 10.1002/jnr.23840 -
Developmental Biology Jan 2017Striatal cholinergic interneurons and basal forebrain cholinergic projection neurons, which together comprise the forebrain cholinergic system, regulate attention,... (Review)
Review
Striatal cholinergic interneurons and basal forebrain cholinergic projection neurons, which together comprise the forebrain cholinergic system, regulate attention, memory, reward pathways, and motor activity through the neuromodulation of multiple brain circuits. The importance of these neurons in the etiology of neurocognitive disorders has been well documented, but our understanding of their specification during embryogenesis is still incomplete. All forebrain cholinergic projection neurons and interneurons appear to share a common developmental origin in the embryonic ventral telencephalon, a region that also gives rise to GABAergic projection neurons and interneurons. Significant progress has been made in identifying the key intrinsic and extrinsic factors that promote a cholinergic fate in this precursor population. However, how cholinergic interneurons and projection neurons differentiate from one another during development, as well as how distinct developmental programs contribute to heterogeneity within those two classes, is not yet well understood. In this review we summarize the transcription factors and signaling molecules known to play a role in the specification and early development of striatal and basal forebrain cholinergic neurons. We also discuss the heterogeneity of these populations and its possible developmental origins.
Topics: Animals; Body Patterning; Cholinergic Neurons; Humans; Neural Stem Cells; Prosencephalon; Signal Transduction; Transcription Factors
PubMed: 27847324
DOI: 10.1016/j.ydbio.2016.11.007 -
Wiley Interdisciplinary Reviews.... Jan 2017The adult human brain is arguably the most complex of biological systems. It contains 86 billion neurons (the information processing cells of the brain) and many more... (Review)
Review
The adult human brain is arguably the most complex of biological systems. It contains 86 billion neurons (the information processing cells of the brain) and many more support cells. The neurons, with the assistance of the support cells, form trillions of connections creating complex, interconnected neural networks that support all human thought, feeling, and action. A challenge for modern neuroscience is to provide a model that accounts for this exquisitely complex and dynamic system. One fundamental part of this model is an account of how the human brain develops. This essay describes two important aspects of this developmental story. The first part of the story focuses on the remarkable and dynamic set of events that unfold during the prenatal period to give rise to cell lineage that form the essential substance of the brain, particularly the structures of the cerebral hemispheres. The second part of the story focuses on the formation of the major brain pathways of the cerebrum, the intricate fiber bundles that connect different populations of neurons to form the information processing systems that support all human thought and action. These two aspects of early brain development provide an essential foundation for understanding how the structure, organization, and functioning of the human brain emerge. WIREs Cogn Sci 2017, 8:e1409. doi: 10.1002/wcs.1409 For further resources related to this article, please visit the WIREs website.
Topics: Humans; Neural Pathways; Neural Stem Cells; Neuroglia; Neurons; Prosencephalon
PubMed: 27906520
DOI: 10.1002/wcs.1409 -
Neurotoxicology and Teratology 2017The majority of commonly used anesthetic agents induce widespread neuronal degeneration in the developing mammalian brain. Downstream, the process appears to involve... (Review)
Review
The majority of commonly used anesthetic agents induce widespread neuronal degeneration in the developing mammalian brain. Downstream, the process appears to involve activation of the oxidative stress-associated mitochondrial apoptosis pathway. Targeting this pathway could result in prevention of anesthetic toxicity in the immature brain. Carbon monoxide (CO) is a gas that exerts biological activity in the developing brain and low dose exposures have the potential to provide neuroprotection. In recent work, low concentration CO exposures limited isoflurane-induced neuronal apoptosis in a dose-dependent manner in newborn mice and modulated oxidative stress within forebrain mitochondria. Because infants and children are routinely exposed to low levels of CO during low-flow general endotracheal anesthesia, such anti-oxidant and pro-survival cellular effects are clinically relevant. Here we provide an overview of anesthesia-related CO exposure, discuss the biological activity of low concentration CO, detail the effects of CO in the brain during development, and provide evidence for CO-mediated inhibition of anesthesia-induced neurotoxicity.
Topics: Animals; Apoptosis; Brain; Carbon Monoxide; Dose-Response Relationship, Drug; Humans; Isoflurane; Mitochondria; Neurotoxicity Syndromes; Oxidative Stress; Prosencephalon
PubMed: 27616667
DOI: 10.1016/j.ntt.2016.09.002 -
Pediatric Radiology Jan 2016Atelencephaly is a rare lethal congenital brain malformation characterized by underdevelopment of the prosencephalon and is often accompanied by the facial features seen... (Review)
Review
Atelencephaly is a rare lethal congenital brain malformation characterized by underdevelopment of the prosencephalon and is often accompanied by the facial features seen in some cases of holoprosencephaly, such as cyclopia. We report a case of atelencephaly in the fetus with characteristic ultrasound findings. In addition, we report the findings on fetal MRI, which have not been previously described in the literature.
Topics: Abnormalities, Multiple; Anencephaly; Diagnosis, Differential; Echoencephalography; Female; Humans; Image Enhancement; Magnetic Resonance Imaging; Male; Prosencephalon; Ultrasonography, Prenatal
PubMed: 26260203
DOI: 10.1007/s00247-015-3440-7 -
Science (New York, N.Y.) Oct 2019Although language, and therefore spoken language or speech, is often considered unique to humans, the past several decades have seen a surge in nonhuman animal studies... (Review)
Review
Although language, and therefore spoken language or speech, is often considered unique to humans, the past several decades have seen a surge in nonhuman animal studies that inform us about human spoken language. Here, I present a modern, evolution-based synthesis of these studies, from behavioral to molecular levels of analyses. Among the key concepts drawn are that components of spoken language are continuous between species, and that the vocal learning component is the most specialized and rarest and evolved by brain pathway duplication from an ancient motor learning pathway. These concepts have important implications for understanding brain mechanisms and disorders of spoken language.
Topics: Animals; Auditory Cortex; Biological Evolution; Brain; Brain Stem; Humans; Language; Learning; Motor Cortex; Neural Pathways; Neurons; Prosencephalon; Speech; Transcriptome; Vocalization, Animal
PubMed: 31604300
DOI: 10.1126/science.aax0287 -
Brain, Behavior and Evolution 2022The amygdala, a complex array of nuclei in the forebrain, controls emotions and emotion-related behaviors in vertebrates. Current research aims to understand the... (Review)
Review
The amygdala, a complex array of nuclei in the forebrain, controls emotions and emotion-related behaviors in vertebrates. Current research aims to understand the amygdala's evolution in ray-finned fish such as zebrafish because of the region's relevance for social behavior and human psychiatric disorders. Clear-cut molecular definitions of the amygdala and its evolutionary-developmental relationship to the one of mammals are critical for zebrafish models of affective disorders and autism. In this review, I argue that the prosomeric model and a focus on the olfactory system's organization provide ideal tools for discovering deep ancestral relationships between the emotional systems of zebrafish and mammals. The review's focus is on the "extended amygdala," which refers to subpallial amygdaloid territories including the central (autonomic) and the medial (olfactory) amygdala required for reproductive and social behaviors. Amphibians, sauropsids, and lungfish share many characteristics with the basic amygdala ground plan of mammals, as molecular and hodological studies have shown. Further exploration of the evolution of the amygdala in basally derived fish vertebrates requires researchers to test these "tetrapod-based" concepts. Historically, this has been a daunting task because the forebrains of basally derived fish vertebrates look very different from those of more familiar tetrapod ones. An extreme case are ray-finned fish (Actinopterygii) like zebrafish because their telencephalon develops through a distinct outward-growing process called eversion. To this day, scientists have struggled to determine how the everted telencephalon compares to non-actinopterygian vertebrates. Using the teleost zebrafish as a genetic model, comparative neurologists began to establish quantifiable molecular definitions that allow direct comparisons between ray-finned fish and tetrapods. In this review, I discuss how the most recent discovery of the zebrafish amygdala ground plan offers an opportunity to identify the developmental constraints of amygdala evolution and function. In addition, I explain how the zebrafish prethalamic eminence (PThE) topologically relates to the medial amygdala proper and the nucleus of the lateral olfactory tract (nLOT). In fact, I consider these previously misinterpreted olfactory structures the most critical missing evolutionary links between actinopterygian and tetrapod amygdalae. In this context, I will also explain why recognizing both the PThE and the nLOT is crucial to understanding the telencephalon eversion. Recognizing these anatomical hallmarks allows direct comparisons of the amygdalae of zebrafish and mammals. Ultimately, the new concepts of the zebrafish amygdala will overcome current dogmas and reach a holistic understanding of amygdala circuits of cognition and emotion in actinopterygians.
Topics: Humans; Animals; Zebrafish; Fishes; Telencephalon; Amygdala; Prosencephalon; Mammals
PubMed: 35760049
DOI: 10.1159/000525669 -
Progress in Neurobiology Nov 2018The brain was long considered an organ that underwent very little change after development. It is now well established that the mammalian central nervous system contains... (Review)
Review
The brain was long considered an organ that underwent very little change after development. It is now well established that the mammalian central nervous system contains neural stem cells that generate progeny that are capable of making new neurons, astrocytes, and oligodendrocytes throughout life. The field has advanced rapidly as it strives to understand the basic biology of these precursor cells, and explore their potential to promote brain repair. The purpose of this review is to present current knowledge about the diversity of neural stem cells in vitro and in vivo, and highlight distinctions between neural stem cell populations, throughout development, and within the niche. A comprehensive understanding of neural stem cell heterogeneity will provide insights into the cellular and molecular regulation of neural development and lifelong neurogenesis, and will guide the development of novel strategies to promote regeneration and neural repair.
Topics: Animals; Humans; Neural Stem Cells; Prosencephalon
PubMed: 29902499
DOI: 10.1016/j.pneurobio.2018.06.005