scholarly journals The hypothalamus predates the origin of vertebrates

2021 ◽  
Vol 7 (18) ◽  
pp. eabf7452
Author(s):  
Laurence A. Lemaire ◽  
Chen Cao ◽  
Peter H. Yoon ◽  
Juanjuan Long ◽  
Michael Levine
Keyword(s):  
Arcuate Nucleus ◽  
Cell Types ◽  
Evolutionary Origin ◽  
Comparative Transcriptome ◽  
Saccus Vasculosus ◽  
Magnocellular Neurons ◽  
Vertebrate Brain ◽  
Specialized Region ◽  
Neuroendocrine Functions ◽  
Relay Neurons

The hypothalamus coordinates neuroendocrine functions in vertebrates. To explore its evolutionary origin, we describe integrated transcriptome/connectome brain maps for swimming tadpoles of Ciona, which serves as an approximation of the ancestral proto-vertebrate. This map features several cell types related to different regions of the vertebrate hypothalamus, including the mammillary nucleus, the arcuate nucleus, and magnocellular neurons. Coronet cells express melanopsin and share additional properties with the saccus vasculosus, a specialized region of the hypothalamus that mediates photoperiodism in nontropical fishes. Comparative transcriptome analyses identified orthologous cell types for mechanosensory switch neurons, and VP+ and VPR+ relay neurons in different regions of the mouse hypothalamus. These observations provide evidence that the hypothalamus predates the evolution of the vertebrate brain. We discuss the possibility that switch neurons, coronet cells, and FoxP+/VPR+ relay neurons comprise a behavioral circuit that helps trigger metamorphosis of Ciona larvae in response to twilight.

Retinal input influences pace of neurogenesis but not cell-type configuration of the visual forebrain

2021 ◽  
Author(s):  
Shachar Sherman ◽  
Koichi Kawakami ◽  
Herwig Baier
Keyword(s):  
Visual Information ◽  
Visual Stimulation ◽  
Ganglion Cells ◽  
Neuronal Cell ◽  
Cell Types ◽  
Vertebrate Brain ◽  
Relative Contribution ◽  
Retinal Input ◽  
And Migration ◽  
The Brain

The brain is assembled during development by both innate and experience-dependent mechanisms1-7, but the relative contribution of these factors is poorly understood. Axons of retinal ganglion cells (RGCs) connect the eye to the brain, forming a bottleneck for the transmission of visual information to central visual areas. RGCs secrete molecules from their axons that control proliferation, differentiation and migration of downstream components7-9. Spontaneously generated waves of retinal activity, but also intense visual stimulation, can entrain responses of RGCs10 and central neurons11-16. Here we asked how the cellular composition of central targets is altered in a vertebrate brain that is depleted of retinal input throughout development. For this, we first established a molecular catalog17 and gene expression atlas18 of neuronal subpopulations in the retinorecipient areas of larval zebrafish. We then searched for changes in lakritz (atoh7-) mutants, in which RGCs do not form19. Although individual forebrain-expressed genes are dysregulated in lakritz mutants, the complete set of 77 putative neuronal cell types in thalamus, pretectum and tectum are present. While neurogenesis and differentiation trajectories are overall unaltered, a greater proportion of cells remain in an uncommitted progenitor stage in the mutant. Optogenetic stimulation of a pretectal area20,21 evokes a visual behavior in blind mutants indistinguishable from wildtype. Our analysis shows that, in this vertebrate visual system, neurons are produced more slowly, but specified and wired up in a proper configuration in the absence of any retinal signals.

scholarly journals Emergence of neuronal diversity during vertebrate brain development

2019 ◽  
Author(s):  
Bushra Raj ◽  
Jeffrey A. Farrell ◽  
Aaron McKenna ◽  
Jessica L. Leslie ◽  
Alexander F. Schier
Keyword(s):  
Brain Development ◽  
Single Cell ◽  
Time Course ◽  
Temporal Dynamics ◽  
Cell Types ◽  
Developmental Time ◽  
Neural Progenitors ◽  
Neuronal Diversity ◽  
Gene Markers ◽  
Vertebrate Brain

ABSTRACTNeurogenesis in the vertebrate brain comprises many steps ranging from the proliferation of progenitors to the differentiation and maturation of neurons. Although these processes are highly regulated, the landscape of transcriptional changes and progenitor identities underlying brain development are poorly characterized. Here, we describe the first developmental single-cell RNA-seq catalog of more than 200,000 zebrafish brain cells encompassing 12 stages from 12 hours post-fertilization to 15 days post-fertilization. We characterize known and novel gene markers for more than 800 clusters across these timepoints. Our results capture the temporal dynamics of multiple neurogenic waves from embryo to larva that expand neuronal diversity from ∼20 cell types at 12 hpf to ∼100 cell types at 15 dpf. We find that most embryonic neural progenitor states are transient and transcriptionally distinct from long-lasting neural progenitors of post-embryonic stages. Furthermore, we reconstruct cell specification trajectories for the retina and hypothalamus, and identify gene expression cascades and novel markers. Our analysis reveal that late-stage retinal neural progenitors transcriptionally overlap cell states observed in the embryo, while hypothalamic neural progenitors become progressively distinct with developmental time. These data provide the first comprehensive single-cell transcriptomic time course for vertebrate brain development and suggest distinct neurogenic regulatory paradigms between different stages and tissues.

Morphological and Membrane Properties of Rat Magnocellular Basal Forebrain Neurons Maintained in Culture

1998 ◽  
Vol 80 (4) ◽  
pp. 1653-1669 ◽  
Author(s):  
J. A. Sim ◽  
T.G.J. Allen
Keyword(s):  
Basal Forebrain ◽  
Cell Types ◽  
Membrane Properties ◽  
Resting Potential ◽  
Inward Rectification ◽  
Delayed Rectifier ◽  
Magnocellular Neurons ◽  
Membrane Hyperpolarization ◽  
Cell Excitability ◽  
Forebrain Neurons

Sim, J. A. and T.G.J. Allen. Morphological and membrane properties of rat magnocellular basal forebrain neurons maintained in culture. J. Neurophysiol. 80: 1653–1669, 1998. Morphological and electrophysiological characteristics of magnocellular neurons from basal forebrain nuclei of postnatal rats (11–14 days old) were examined in dissociated cell culture. Neurons were maintained in culture for periods of 5–27 days, and 95% of magnocellular (>23 μm diam) neurons stained positive with acetylcholinesterase histochemistry. With the use of phase contrast microscopy, four morphological subtypes of magnocellular neurons could be distinguished according to the shape of their soma and pattern of dendritic branching. Corresponding passive and active membrane properties were investigated with the use of whole cell configuration of the patch-clamp technique. Neurons of all cell types displayed a prominent (6–39 mV; 6.7–50 ms duration) spike afterdepolarization (ADP), which in some cells reached firing threshold. The ADP was voltage dependent, increasing in amplitude and decreasing in duration with membrane hyperpolarization with an apparent reversal potential of −59 ± 2.3 (SE) mV. Elevating [Ca2+]o (2.5–5.0 mM) or prolonging spike repolarization with 10 mM tetraethylammonium (TEA) or 1 mM 4-aminopyridine (4-AP), potentiated the ADP while it was inhibited by reducing [Ca2+]o (2.5–1 mM) or superfusion with Cd2+ (100 μM). The ADP was selectively inhibited by amiloride (0.1–0.3 mM or Ni2+ 10 μM) but unaffected by nifedipine (3 μM), ω-conotoxin GVIA (100 nM) or ω-agatoxin IVA (200 nM), indicating that Ca2+ entry was through T-type Ca2+ channels. After inhibition of the ADP with amiloride (300 μM), depolarization to less than −65 mV revealed a spike afterhyperpolarization (AHP) with both fast and slow components that could be inhibited by 4-AP (1 mM) and Cd2+ (100 μM), respectively. In all cell types, current-voltage relationships exhibited inward rectification at hyperpolarized potentials ≥ E K (approximately −90 mV). Application of Cs+ (0.1–1 mM) or Ba2+ (1–10 μM) selectively inhibited inward rectification but had no effect on resting potential or cell excitability. At higher concentrations, Ba2+ (>10 μM) also inhibited an outward current tonically active at resting potential ( V H −70 mV), which under current-clamp conditions resulted in small membrane depolarization (3–10 mV) and an increase in cell excitability. Depolarizing voltage commands from prepulse potential of −90 mV ( V H −70 mV) in the presence of tetrodotoxin (0.5 μM) and Cd2+ (100 μM) to potentials between −40 and +40 mV cause voltage activation of both transient A-type and sustained delayed rectifier-type outward currents, which could be selectively inhibited by 4-AP (0.3–3 mM) and TEA (1–3 mM), respectively. These results show that, although acetylcholinesterase-positive magnocellular basal forebrain neurons exhibit considerable morphological heterogeneity, they have very similar and characteristic electrophysiological properties.

scholarly journals Rapid Modulation of Aromatase Activity in the Vertebrate Brain

2013 ◽  
Vol 7 ◽  
pp. JEN.S11268 ◽  
Author(s):  
Thierry D. Charlier ◽  
Charlotte A. Cornil ◽  
Jacques Balthazart
Keyword(s):  
Amino Acids ◽  
Enzymatic Activity ◽  
Kinase Inhibitors ◽  
Cell Types ◽  
Protein Kinase Inhibitors ◽  
Site Directed Mutagenesis ◽  
General Mechanism ◽  
Aromatase Activity ◽  
Vertebrate Brain ◽  
Rapid Modulation

Numerous steroid hormones, including 17β-estradiol (E2), activate rapid and transient cellular, physiological, and behavioral changes in addition to their well-described genomic effects. Aromatase is the key-limiting enzyme in the production of estrogens, and the rapid modulation of this enzymatic activity could produce rapid changes in local E2 concentrations. The mechanisms that might mediate such rapid enzymatic changes are not fully understood but are currently under intense scrutiny. Recent studies in our laboratory indicate that brain aromatase activity is rapidly inhibited by an increase in intracellular calcium concentration resulting from potassium-induced depolarization or from the activation of glutamatergic receptors. Phosphorylating conditions also reduce aromatase activity within minutes, and this inhibition is blocked by the addition of multiple protein kinase inhibitors. This rapid modulation of aromatase activity by phosphorylating conditions is a general mechanism observed in different cell types and tissues derived from a variety of species, including human aromatase expressed in various cell lines. Phosphorylation processes affect aromatase itself and do not involve changes in aromatase protein concentration. The control of aromatase activity by multiple kinases suggests that several amino acids must be concomitantly phosphorylated to modify enzymatic activity but site-directed mutagenesis of several amino acids alone or in combination has not to date revealed the identity of the targeted residue(s). Altogether, the phosphorylation processes affecting aromatase activity provide a new general mechanism by which the concentration of estrogens can be rapidly altered in the brain.

scholarly journals Nicotine excites hypothalamic arcuate anorexigenic proopiomelanocortin neurons and orexigenic neuropeptide Y neurons: similarities and differences

2011 ◽  
Vol 106 (3) ◽  
pp. 1191-1202 ◽  
Author(s):  
Hao Huang ◽  
Youfen Xu ◽  
Anthony N. van den Pol
Keyword(s):  
Weight Loss ◽  
Neuropeptide Y ◽  
Arcuate Nucleus ◽  
Input Resistance ◽  
Cell Types ◽  
Underlying Mechanism ◽  
Synaptic Activity ◽  
Cognitive Arousal ◽  
Hypothalamic Arcuate Nucleus ◽  
Prevalence Of Obesity

Two of the biggest health problems facing us today are addiction to nicotine and the increased prevalence of obesity. Interestingly, nicotine attenuates obesity, but the underlying mechanism is not clear. Here we address the hypothesis that if weight-reducing actions of nicotine are mediated by anorexigenic proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus, nicotine should excite these cells. Nicotine at concentrations similar to those found in smokers, 100–1,000 nM, excited POMC cells by mechanisms based on increased spike frequency, depolarization of membrane potential, and opening of ion channels. This was mediated by activation of both α7 and α4β2 nicotinic receptors; by itself, this nicotine-mediated excitation could explain weight loss caused by nicotine. However, in control experiments nicotine also excited the orexigenic arcuate nucleus neuropeptide Y (NPY) cells. Nicotine exerted similar actions on POMC and NPY cells, with a slightly greater depolarizing action on POMC cells. Immunocytochemistry revealed cholinergic axons terminating on both cell types. Nicotine actions were direct in both cell types, with nicotine depolarizing the membrane potentials and reducing input resistance. We found no differences in the relative desensitization to nicotine between POMC and NPY neurons. Nicotine inhibited excitatory synaptic activity recorded in NPY, but not POMC, cells. Nicotine also excited hypocretin/orexin neurons that enhance cognitive arousal, but the responses were smaller than in NPY or POMC cells. Together, these results indicate that nicotine has a number of similar actions, but also a few different actions, on POMC and NPY neurons that could contribute to the weight loss associated with smoking.

scholarly journals Single-cell RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates and humans

2020 ◽  
Author(s):  
Trygve E. Bakken ◽  
Cindy T.J. van Velthoven ◽  
Vilas Menon ◽  
Rebecca D. Hodge ◽  
Zizhen Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Visual Information ◽  
Cell Types ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Cortical Projection ◽  
Significant Differential Expression ◽  
Cellular Expression ◽  
Dominant Feature ◽  
Parvocellular Neurons ◽  
Relay Neurons

ABSTRACTAbundant anatomical and physiological evidence supports the presence of at least three distinct types of relay glutamatergic neurons in the primate dorsal lateral geniculate nucleus (dLGN) of the thalamus, the brain region that conveys visual information from the retina to the primary visual cortex. Relay neuron diversity has also been described in the mouse dLGN (also known as LGd). Different types of relay neurons in mice, humans and macaques have distinct morphologies, distinct connectivity patterns, and convey different aspects of visual information to the cortex. To investigate the molecular underpinnings of these cell types, and how these relate to other cellular properties and differences in dLGN between human, macaque, and mice, we profiled gene expression in single nuclei and cells using RNA-sequencing. These efforts identified four distinct types of relay neurons in the primate dLGN, magnocellular neurons, parvocellular neurons, and two cell types expressing canonical marker genes for koniocellular neurons. Surprisingly, despite extensive documented morphological and physiological differences between magno- and parvocellular neurons, we identified few genes with significant differential expression between transcriptomic cell types corresponding to these two neuronal populations. We also detected strong donor-specific gene expression signatures in both macaque and human relay neurons. Likewise, the dominant feature of relay neurons of the adult mouse dLGN is high transcriptomic similarity, with an axis of heterogeneity that aligns with core vs. shell portions of mouse dLGN. Together, these data show that transcriptomic differences between principal cell types in the mature mammalian dLGN are subtle relative to striking differences in morphology and cortical projection targets. Finally, we align cellular expression profiles across species and find homologous types of relay neurons in macaque and human, and distinct relay neurons in mouse.

Abstract 077: Angiotensinogen in Neurons of the Arcuate Nucleus May Regulate Metabolic Rate in Mice

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Sarah A Sapouckey ◽  
Guorui Deng ◽  
Kristin E Claflin ◽  
Katherine N Gibson-Corley ◽  
Justin L Grobe
Keyword(s):  
Metabolic Rate ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Resting Metabolic Rate ◽  
Neuronal Cell ◽  
Cell Types ◽  
Chow Diet ◽  
Gamma Aminobutyric Acid ◽  
Gaba Synthesis ◽  
Local Release

Recent studies from our laboratory have demonstrated that angiotensin II (ANG) type 1A receptors (AT1A) within the arcuate nucleus, expressed in the subset of neurons which express both the leptin receptor (LepR) and agouti-related peptide (AgRP), are critically involved in the control of thermogenic adipose sympathetic nerve activity (SNA) and resting metabolic rate (RMR) by leptin. This mechanism appears to involve AT1A-mediated suppression of gamma-aminobutyric acid (GABA) synthesis and packaging in AgRP neurons of the arcuate nucleus (ARC). It remains unclear, however, how leptin/LepR signaling results in AT1A activation within AgRP neurons. We hypothesize that LepR signaling results in increased transcription and local release of angiotensinogen (AGT) within the ARC, and consequently increased autocrine or paracrine ANG signaling within the ARC. Fluorescent in situ hybridization (RNAscope) uncovered expression of AGT mRNA in various cells of the ARC of C57BL/6J mice, including cells expressing mRNA for LepR, AgRP, proopiomelanocortin (POMC), insulin II, or glial fibrillary acidic protein, supporting local generation of AGT within the ARC. In silico re-analysis of a publically-available gene expression dataset interrogating individual cell types of the mouse hypothalamus (GSE74672) similarly uncovered expression of AGT in astrocytes, microglia, and many neuronal cell types of the ARC, including those expressing AgRP and POMC. Stimulation of immortalized mouse hypothalamic AgRP-like cell cultures (N47) with leptin may increase AGT mRNA (100 nM, 4 hrs; n=4 passages, 1.0 (0.6-1.8) vs 2.0 (1.2-3.6) fold, p=0.19). Further, using Cre-lox technology, mice lacking AGT in LepR- or AgRP-expressing cells (AGT LepR-KO or AGT AgRP-KO mice) were generated. In females at 8 weeks of age fed a chow diet (Teklad 7013), trends toward increased fat mass were noted (control n=28, 0.7±0.1; AGT LepR-KO n=2, 1.0±0.5; AGT AgRP-KO n=3, 1.0±0.2 g), despite normal food intake (13.5±0.6, 16.3±0.0, 12.4±0.8 kcal/d) and digestive efficiency (79±1, 83±0, 80±1 %). Collectively, these findings support local production of ANG peptides within the ARC, and may indicate transcriptional regulation of AGT by leptin and a role for ARC AGT in the control of energy expenditure.

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