Complete morphologies of basal forebrain cholinergic neurons in the mouse
TLDR
Using genetically-directed sparse labeling, the complete morphologies of basal forebrain cholinergic neurons in the mouse are characterized and Calculations based on published morphometric data indicate that basal fore brain cholinergy neurons in humans have a mean axon length of ∼100 meters.Abstract:
The human brain is made up of roughly 80 to 100 billion neurons, organized into extensive networks. Each neuron consists of a number of components: a cell body, which contains the nucleus; numerous short protrusions from the cell body called dendrites; and a long thin structure called an axon that carries the electrical signals generated in the cell body and the dendrites to the next neuron in the network. One of the most studied networks in the human brain is the basal forebrain network, which is made up of large neurons that communicate with one another using a chemical transmitter called acetylcholine. This network has a key role in cognition, and its neurons are among the first to degenerate in Alzheimer's disease. However, relatively little is known about the structure of these ‘cholinergic’ neurons because their large size makes them difficult to study using standard techniques. Now, Wu et al. have visualized, for the first time, the complete 3D structure of cholinergic neurons in the mouse forebrain. The mice in question had been genetically modified so that only ten or so of their many thousands of cholinergic neurons expressed a distinctive ‘marker’ protein. This made it possible to distinguish these neurons from surrounding brain tissue in order to visualize their structures. The resulting pictures clearly illustrate the neurons' complexity, with individual axons in adult mice displaying up to 1000 branches. Measurements showed that each cholinergic axon in the mouse brain is roughly 30 centimeters long, even though the brain itself is less than 2 centimeters from front to back. Based on measurements by other researchers, Wu et al. calculated that the axons of single cholinergic neurons in the human brain are about 100 meters long on average. The extreme length and complex branching structure of cholinergic forebrain neurons helps to explain why each neuron is able to modulate the activity of many others in the network. It could also explain their vulnerability to degeneration, as the need to transport materials over such long distances may limit the ability of these neurons to respond to damage.read more
Citations
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Selective neuronal vulnerability in Parkinson disease.
TL;DR: The evidence for and against the spreading LP model are discussed, as well as evidence that cell-autonomous factors govern both α-syn pathology and neuronal death.
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Basal Forebrain Cholinergic Circuits and Signaling in Cognition and Cognitive Decline
TL;DR: This Review attempts to identify areas of controversy, as well as consensus, on what is and is not yet known about how cholinergic signaling in the CNS contributes to normal cognitive processes, and delineates the findings from recent work on the extent to which Dysfunction of Cholinergic circuits contributes to cognitive decline associated with neurodegenerative disorders.
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A platform for brain-wide imaging and reconstruction of individual neurons
Michael N. Economo,Nathan G. Clack,Luke D. Lavis,Charles R. Gerfen,Charles R. Gerfen,Karel Svoboda,Eugene W. Myers,Eugene W. Myers,Jayaram Chandrashekar +8 more
TL;DR: A platform for high-resolution, three-dimensional fluorescence imaging of complete tissue volumes that enables the visualization and reconstruction of long-range axonal arbors is introduced and the power of this approach is demonstrated by reconstructing the axonalArbors of multiple neurons in the motor cortex across a single mouse brain.
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Mitostasis in Neurons: Maintaining Mitochondria in an Extended Cellular Architecture
TL;DR: Both long-range transport and local processing are at work in achieving neuronal mitostasis-the maintenance of an appropriately distributed pool of healthy mitochondria for the duration of a neuron's life.
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Reconstruction of 1,000 Projection Neurons Reveals New Cell Types and Organization of Long-Range Connectivity in the Mouse Brain
Johan Winnubst,Erhan Bas,Tiago Ferreira,Zhuhao Wu,Michael N. Economo,Patrick Edson,Ben J. Arthur,Christopher M. Bruns,Konrad Rokicki,David Schauder,Donald J. Olbris,Sean D. Murphy,David G. Ackerman,Cameron Arshadi,Perry Baldwin,Regina Blake,Ahmad Elsayed,Mashtura Hasan,Daniel Ramirez,Bruno Dos Santos,Monet Weldon,Amina Zafar,Joshua T. Dudman,Charles R. Gerfen,Adam W. Hantman,Wyatt Korff,Scott M. Sternson,Nelson Spruston,Karel Svoboda,Jayaram Chandrashekar +29 more
TL;DR: A robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain are presented and axonal shapes revealed previously unknown subtypes of projection neurons and suggest organizational principles of long-range connectivity.
References
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Book
The Mouse Brain in Stereotaxic Coordinates
TL;DR: The 3rd edition of this atlas is now in more practical 14"x11" format for convenient lab use and includes a CD of all plates and diagrams, as well as Adobe Illustrator files of the diagrams, and a variety of additional useful material.
Book
The rat nervous system
TL;DR: The present work focuses on the development of brain Stem Systems Involved in the Blink Reflex, Feeding Mechanisms, and Micturition of the Spinal Cord, which are involved in the selection of somatic and emotional components of the Motor System in Mammals.
Journal ArticleDOI
Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase
Joanna L. Jankowsky,Joanna L. Jankowsky,Daniel J. Fadale,Jeffrey Anderson,Guilian Xu,Victoria Gonzales,Nancy A. Jenkins,Neal G. Copeland,Michael K. Lee,Linda H. Younkin,Steven L. Wagner,Steven G. Younkin,David R. Borchelt +12 more
TL;DR: A direct correlation between the concentration of Aβ42 and the rate of amyloid deposition is demonstrated and suggests that PS1 variants do not simply alter the preferred cleavage site for γ-secretase, but rather that they have more complex effects on the regulation of ιsecretase and its access to substrates.
Journal ArticleDOI
Cortical map reorganization enabled by nucleus basalis activity.
TL;DR: It is demonstrated that episodic electrical stimulation of the nucleus basalis, paired with an auditory stimulus, results in a massive progressive reorganization of the primary auditory cortex in the adult rat, suggesting that input characteristics may be able to drive appropriate alterations of receptive fields independently of explicit knowledge of the task.
Journal ArticleDOI
ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models.
Paige E. Cramer,John R. Cirrito,Daniel W. Wesson,Daniel W. Wesson,C. Y. Daniel Lee,J. Colleen Karlo,Adriana E. Zinn,Brad T. Casali,Jessica L. Restivo,Whitney D. Goebel,Michael J. James,Kurt R. Brunden,Donald A. Wilson,Gary E. Landreth +13 more
TL;DR: Oral administration of the RXR agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Aβ within hours in an apoE-dependent manner, and stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function.