scholarly journals Fast retrograde access to projection neuron circuits underlying vocal learning in songbirds

2020 ◽  
Author(s):  
DN Düring ◽  
F Dittrich ◽  
MD Rocha ◽  
RO Tachibana ◽  
C Mori ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Morphological Analysis ◽  
Vocal Learning ◽  
Projection Neuron ◽  
Neuron Populations ◽  
And Function ◽  
Genetic Targeting ◽  
Learning Circuits ◽  
Specific Neuron

SummaryUnderstanding the structure and function of neural circuits underlying speech and language is a vital step towards better treatments for diseases of these systems. Songbirds, among the few animal orders that share with humans the ability to learn vocalizations from a conspecific, have provided many insights into the neural mechanisms of vocal development. However, research into vocal learning circuits has been hindered by a lack of tools for rapid genetic targeting of specific neuron populations to meet the quick pace of developmental learning. Here, we present a new viral tool that enables fast and efficient retrograde access to projection neuron populations. In zebra finches, Bengalese finches, canaries, and mice, we demonstrate fast retrograde labeling of cortical or dopaminergic neurons. We further demonstrate the suitability of our construct for detailed morphological analysis, for in vivo imaging of calcium activity, and for multicolor brainbow labeling.

scholarly journals FOXP2 exhibits projection neuron class specific expression, but is not required for multiple aspects of cortical histogenesis

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ryan J Kast ◽  
Alexandra L Lanjewar ◽  
Colton D Smith ◽  
Pat Levitt
Keyword(s):  
Expression Patterns ◽  
Projection Neuron ◽  
Specific Expression ◽  
Neuron Populations ◽  
Mouse Cortex ◽  
Molecular Studies ◽  
Multiple Species ◽  
Molecular Phenotypes ◽  
And Function

The expression patterns of the transcription factor FOXP2 in the developing mammalian forebrain have been described, and some studies have tested the role of this protein in the development and function of specific forebrain circuits by diverse methods and in multiple species. Clinically, mutations in FOXP2 are associated with severe developmental speech disturbances, and molecular studies indicate that impairment of Foxp2 may lead to dysregulation of genes involved in forebrain histogenesis. Here, anatomical and molecular phenotypes of the cortical neuron populations that express FOXP2 were characterized in mice. Additionally, Foxp2 was removed from the developing mouse cortex at different prenatal ages using two Cre-recombinase driver lines. Detailed molecular and circuit analyses were undertaken to identify potential disruptions of development. Surprisingly, the results demonstrate that Foxp2 function is not required for many functions that it has been proposed to regulate, and therefore plays a more limited role in cortical development than previously thought.

scholarly journals The segregation of vocal circuits solves a credit assignment problem associated with multi-objective reinforcement learning

2017 ◽  
Author(s):  
Don Murdoch ◽  
Ruidong Chen ◽  
Jesse Goldberg
Keyword(s):  
Motor System ◽  
Vocal Learning ◽  
Place Learning ◽  
Credit Assignment ◽  
Strobe Light ◽  
Multi Objective ◽  
Motor Circuits ◽  
And Function ◽  
Learning Circuits ◽  
Double Dissociations

AbstractMotor circuits vary in topographic organization, ranging from a coarse relationship between neuron location and function to highly localized regions controlling specific behaviors. For unclear reasons, vocal learning circuits lie at this second extreme: they repeatedly evolved to be spatially segregated from other parts of the motor system. Here we show that spatially segregated motor circuits can solve a specific problem that arises when an animal tries to learn two things at once. We trained songbirds in vocal and place learning paradigms with brief strobe light flashes and noise bursts. Strobe light negatively reinforced place learning but did not affect song syllable learning. Noise bursts positively reinforced place preference but negatively reinforced syllable learning. These double dissociations indicate that vocalization-related reinforcement signals specifically target the vocal motor system, while place-related reinforcement signals specifically target the navigation system. Non-global, target-specific reinforcement signals have established utility in machine implementation of multi-objective learning. In vocal learners, such signals could enable an animal to practice vocalizing as it does other things such as forage for food or learn to walk.

scholarly journals Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain

2016 ◽  
Vol 113 (23) ◽  
pp. 6544-6549 ◽  
Author(s):  
Wen Li ◽  
Elisabet Englund ◽  
Håkan Widner ◽  
Bengt Mattsson ◽  
Danielle van Westen ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Histopathological Analysis ◽  
Positron Emission ◽  
Clinical Benefits ◽  
And Function ◽  
Motor Improvement ◽  
Host Brain

Clinical trials using cells derived from embryonic ventral mesencephalon have shown that transplanted dopaminergic neurons can survive and function in the long term, as demonstrated by in vivo brain imaging using 18F-fluorodopa and 11C-raclopride positron emission tomography. Here we report the postmortem analysis of a patient with Parkinson’s disease who 24 y earlier underwent unilateral transplantation of embryonic dopaminergic neurons in the putamen and subsequently exhibited major motor improvement and recovery of striatal dopaminergic function. Histopathological analysis showed that a dense, near-normal graft-derived dopaminergic reinnervation of the putamen can be maintained for a quarter of a century despite severe host brain pathology and with no evidence of immune response. In addition, ubiquitin- and α-synuclein–positive inclusions were seen, some with the appearance of typical Lewy bodies, in 11–12% of the grafted dopaminergic neurons, reflecting the spread of pathology from the host brain to the transplants. Because the clinical benefits induced by transplantation in this patient were gradually lost after 14 y posttransplantation, our findings provide the first reported evidence, to our knowledge, that even a viable dopaminergic graft giving rise to extensive striatal reinnervation may lose its efficacy if widespread degenerative changes develop in the host brain.

scholarly journals Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids

2019 ◽  
Author(s):  
Lisa M. Smits ◽  
Stefano Magni ◽  
Kamil Grzyb ◽  
Paul MA. Antony ◽  
Rejko Krüger ◽  
...  
Keyword(s):  
Single Cell ◽  
Dopaminergic Neurons ◽  
Neuronal Cell ◽  
Cell Types ◽  
Human Stem Cell ◽  
Glutamatergic Neurons ◽  
And Function ◽  
Excellent Tool

AbstractHuman stem cell-derived organoids have great potential for modelling physiological and pathological processes. They recapitulatein vitrothe organisation and function of a respective organ or part of an organ. Human midbrain organoids (hMOs) have been described to contain midbrain-specific dopaminergic neurons that release the neurotransmitter dopamine. However, the human midbrain contains also additional neuronal cell types, which are functionally interacting with each other. Here, we analysed hMOs at high-resolution by means of single-cell RNA-sequencing (scRNA-seq), imaging and electrophysiology to unravel cell heterogeneity. Our findings demonstrate that hMOs show essential neuronal functional properties as spontaneous electrophysiological activity of different neuronal subtypes, including dopaminergic, GABAergic, and glutamatergic neurons. Recapitulating thesein vivofeatures makes hMOs an excellent tool forin vitrodisease phenotyping and drug discovery.

scholarly journals FOXP2 exhibits projection neuron class specific expression, but is not required for multiple aspects of cortical histogenesis

2019 ◽  
Author(s):  
Ryan J Kast ◽  
Alexandra L Lanjewar ◽  
Colton D Smith ◽  
Pat Levitt
Keyword(s):  
Expression Patterns ◽  
Projection Neuron ◽  
Specific Expression ◽  
Neuron Populations ◽  
Mouse Cortex ◽  
Molecular Studies ◽  
Multiple Species ◽  
Molecular Phenotypes ◽  
And Function

AbstractThe expression patterns of the transcription factor FOXP2 in the developing mammalian forebrain have been described, and some studies have tested the role of this protein in the development and function of specific forebrain circuits by diverse methods and in multiple species. Clinically, mutations in FOXP2 are associated with severe developmental speech disturbances, and molecular studies indicate that impairment of Foxp2 may lead to dysregulation of genes involved in forebrain histogenesis. Here, anatomical and molecular phenotypes of the cortical neuron populations that express FOXP2 were characterized in mice. Additionally, Foxp2 was removed from the developing mouse cortex at different prenatal ages using two Cre-recombinase driver lines. Detailed molecular and circuit analyses were undertaken to identify potential disruptions of development. Surprisingly, the results demonstrate that Foxp2 function is not required for many functions that it has been proposed to regulate, and therefore plays a more limited role in cortical development than previously thought.

scholarly journals SKP-SCs transplantation alleviates 6-OHDA-induced dopaminergic neuronal injury by modulating autophagy

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Chengxiao Ma ◽  
Wen Zhang ◽  
Wengcong Wang ◽  
Jiabing Shen ◽  
Kefu Cai ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Cell Transplantation ◽  
Dopaminergic Neurons ◽  
Therapeutic Option ◽  
In Vivo Studies ◽  
And Function ◽  
Disease Cell ◽  
Neuronal Autophagy

AbstractParkinson’s disease is a common neurodegenerative disease. Cell transplantation is a promising therapeutic option for improving the survival and function of dopaminergic neurons, but the mechanisms underlying the interaction between the transplanted cells and the recipient neurons remain to be studied. In this study, we investigated the effects of skin precursor cell-derived Schwann cells (SKP-SCs) directly cocultured with 6-OHDA-injured dopaminergic neurons in vitro and of SKP-SCs transplanted into the brains of 6-OHDA-induced PD mice in vivo. In vitro and in vivo studies revealed that SKP-SCs could reduce the damage to dopaminergic neurons by enhancing self-autophagy and modulating neuronal autophagy. Thus, the present study provides the first evidence that cell transplantation mitigates 6-OHDA-induced damage to dopaminergic neurons by enhancing self-autophagy, suggesting that earlier transplantation of Schwann cells might help alleviate the loss of dopaminergic neurons.

scholarly journals Generation of a DAT-Flp mouse line for intersectional genetic targeting of dopamine neuron subpopulations

2020 ◽  
Author(s):  
Daniel J. Kramer ◽  
Polina Kosillo ◽  
Drew Friedmann ◽  
David Stafford ◽  
Liqun Luo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dopaminergic Neurons ◽  
Single Gene ◽  
Dopamine Neurons ◽  
Mouse Line ◽  
Flp Recombinase ◽  
And Function ◽  
Genetic Targeting ◽  
The Brain ◽  
Mouse Lines

AbstractDopamine neurons project to diverse regions throughout the brain to modulate various brain processes and behaviors. It is increasingly appreciated that dopamine neurons are heterogeneous in their gene expression, circuitry, physiology, and function. Current approaches to target dopamine neurons are largely based on single gene drivers, which either label all dopamine neurons, or mark a sub-set but concurrently label non-dopaminergic neurons. Here we establish a novel mouse line in which Flp recombinase is knocked-in to the endogenous Slc6a3 (dopamine active transporter, DAT) locus. DAT-Flp mice can be used with various Cre-expressing mouse lines to efficiently and selectively label dopaminergic subpopulations using Cre/Flp-dependent intersectional strategies. We demonstrate the utility of this approach by crossing DAT-Flp mice with NEX-Cre mice, to specifically label Neurod6-expressing dopamine neurons that project to the nucleus accumbens medial shell. DAT-Flp mice represent a novel tool, which will help parse the diverse functions mediated by dopaminergic circuits.

scholarly journals Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids

2020 ◽  
Vol 382 (3) ◽  
pp. 463-476 ◽  
Author(s):  
Lisa M. Smits ◽  
Stefano Magni ◽  
Kaoru Kinugawa ◽  
Kamil Grzyb ◽  
Joachim Luginbühl ◽  
...  
Keyword(s):  
Single Cell ◽  
Dopaminergic Neurons ◽  
Neuronal Cell ◽  
Cell Types ◽  
Human Stem Cell ◽  
Electrophysiological Activity ◽  
And Function ◽  
Excellent Tool

AbstractHuman stem cell-derived organoids have great potential for modelling physiological and pathological processes. They recapitulate in vitro the organization and function of a respective organ or part of an organ. Human midbrain organoids (hMOs) have been described to contain midbrain-specific dopaminergic neurons that release the neurotransmitter dopamine. However, the human midbrain contains also additional neuronal cell types, which are functionally interacting with each other. Here, we analysed hMOs at high-resolution by means of single-cell RNA sequencing (scRNA-seq), imaging and electrophysiology to unravel cell heterogeneity. Our findings demonstrate that hMOs show essential neuronal functional properties as spontaneous electrophysiological activity of different neuronal subtypes, including dopaminergic, GABAergic, glutamatergic and serotonergic neurons. Recapitulating these in vivo features makes hMOs an excellent tool for in vitro disease phenotyping and drug discovery.

Osseointegration interface of calcified bone and endosseous implants

1992 ◽  
Vol 50 (2) ◽  
pp. 1096-1097
Author(s):  
K.E. Krizan ◽  
J.E. Laffoon ◽  
M.J. Buckley
Keyword(s):  
Structure And Function ◽  
Titanium Implants ◽  
En Bloc ◽  
Endosseous Implants ◽  
Ultrastructural Studies ◽  
The Past ◽  
Cacodylate Buffer ◽  
One Year ◽  
And Function

With increase use of tissue-integrated prostheses in recent years it is a goal to understand what is happening at the interface between haversion bone and bulk metal. This study uses electron microscopy (EM) techniques to establish parameters for osseointegration (structure and function between bone and nonload-carrying implants) in an animal model. In the past the interface has been evaluated extensively with light microscopy methods. Today researchers are using the EM for ultrastructural studies of the bone tissue and implant responses to an in vivo environment. Under general anesthesia nine adult mongrel dogs received three Brånemark (Nobelpharma) 3.75 × 7 mm titanium implants surgical placed in their left zygomatic arch. After a one year healing period the animals were injected with a routine bone marker (oxytetracycline), euthanized and perfused via aortic cannulation with 3% glutaraldehyde in 0.1M cacodylate buffer pH 7.2. Implants were retrieved en bloc, harvest radiographs made (Fig. 1), and routinely embedded in plastic. Tissue and implants were cut into 300 micron thick wafers, longitudinally to the implant with an Isomet saw and diamond wafering blade [Beuhler] until the center of the implant was reached.

Functional characterization of human brown adipose tissue metabolism

2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Functional Characterization ◽  
Human Infants ◽  
Positron Emission ◽  
Brown Adipose ◽  
Treatment Of Obesity ◽  
And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

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