scholarly journals Generation of a whole-brain atlas for the cholinergic system and mesoscopic projectome analysis of basal forebrain cholinergic neurons

2017 ◽  
Vol 115 (2) ◽  
pp. 415-420 ◽  
Author(s):  
Xiangning Li ◽  
Bin Yu ◽  
Qingtao Sun ◽  
Yalun Zhang ◽  
Miao Ren ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Cholinergic System ◽  
Cholinergic Neurons ◽  
Brain Atlas ◽  
Projection Area ◽  
Single Neurons ◽  
Whole Brain ◽  
Cognitive Behaviors ◽  
Optical Images ◽  
The Brain

The cholinergic system in the brain plays crucial roles in regulating sensory and motor functions as well as cognitive behaviors by modulating neuronal activity. Understanding the organization of the cholinergic system requires a complete map of cholinergic neurons and their axon arborizations throughout the entire brain at the level of single neurons. Here, we report a comprehensive whole-brain atlas of the cholinergic system originating from various cortical and subcortical regions of the mouse brain. Using genetically labeled cholinergic neurons together with whole-brain reconstruction of optical images at 2-μm resolution, we obtained quantification of the number and soma volume of cholinergic neurons in 22 brain areas. Furthermore, by reconstructing the complete axonal arbors of fluorescently labeled single neurons from a subregion of the basal forebrain at 1-μm resolution, we found that their projections to the forebrain and midbrain showed neuronal subgroups with distinct projection specificity and diverse arbor distribution within the same projection area. These results suggest the existence of distinct subtypes of cholinergic neurons that serve different regulatory functions in the brain and illustrate the usefulness of complete reconstruction of neuronal distribution and axon projections at the mesoscopic level.

scholarly journals Does senile impairment of cholinergic system in rats concern only disturbances in cholinergic phenotype or the progressive degeneration of neuronal cell bodies?

2000 ◽  
Vol 47 (2) ◽  
pp. 313-330 ◽  
Author(s):  
G Niewiadomska ◽  
J Wyrzykowska ◽  
M Chechłacz
Keyword(s):  
Basal Forebrain ◽  
Cholinergic System ◽  
Neuronal Cell ◽  
Cholinergic Neurons ◽  
Image Analyzer ◽  
Trophic Effect ◽  
Neuronal Cell Bodies ◽  
Male Wistar Rats ◽  
Old Rats ◽  
Cholinergic Phenotype

The trophic effect of continuous intraventricular infusion of nerve growth factor (NGF) on morphology of the basal forebrain (BF) cholinergic neurons was tested in 4- and 28-month-old male Wistar rats. All studies were conducted using behaviorally uncharacterized animals from the same breeding colony. Immunohistochemical procedure for choline acetyltransferase (ChAT) and p75NTR receptor has been applied to identify cholinergic cells in the structures of basal forebrain (BF). Using a quantitative image analyzer, morphometric and densitometric parameters of ChAT- and p75NTR-positive cells were measured immediately after cessation of NGF infusion. In 28-month-old non-treated rats the number of intensively ChAT-positive cells in all forebrain structures was reduced by 50-70% as compared with young animals. The remaining ChAT-positive cells appeared shrunken and the neuropil staining was NTR markedly reduced. In contrast, the same neurons when stained for p75 were numerous and distinctly visible with perfect morphology. Analysis of Nissl stained sections also showed that 28-month-old rats did not display significant losses of neuronal cell bodies. NGF restored the number of intensely stained ChAT-positive cells to about 90% of that for young controls and caused a significant increase in size of those cells in 28-month-old rats as compared with the control, age-matched group. NGF did not influence the morphology of p75NTR-positive neurons, which were well labeled, irrespective of treatment and age of the rats. In 4-month-old rats, NGF infusion decreased the intensity of both ChAT and p75NTR immunostaining. These data provide some evidence for preservation of BF cholinergic neurons from atrophy during aging and indicate that senile impairment of the cholinergic system in rats concerns decrease in ChAT-protein expression rather than an acute degeneration of neuronal cell bodies. Treatment with NGF resulted in restoration of cholinergic phenotype in the BF neurons of aged rats. However, the present study also rises issue of possible detrimental effects of NGF in young normal animals.

scholarly journals Whole brain mapping of glutamate in adult and old primates at 11.7T

2021 ◽  
Author(s):  
Clement M Garin ◽  
Nachiket A. Nadkarni ◽  
Jeremy Pepin ◽  
Julien Flament ◽  
Marc Dhenain
Keyword(s):  
Magnetic Field ◽  
Nucleus Accumbens ◽  
High Magnetic Field ◽  
Basal Forebrain ◽  
Chemical Exchange ◽  
Chemical Exchange Saturation Transfer ◽  
Whole Brain ◽  
Cortical Areas ◽  
Age Related ◽  
The Brain

Glutamate is the amino acid with the highest cerebral concentration. It plays a central role in brain metabolism. It is also the principal excitatory neurotransmitter in the brain and is involved in multiple cognitive functions. Alterations of the glutamatergic system may contribute to the pathophysiology of many neurological disorders. For example, changes of glutamate availability are reported in rodents and humans during Alzheimer's and Huntington's diseases, epilepsy as well as during aging. Most studies evaluating cerebral glutamate have used invasive or spectroscopy approaches focusing on specific brain areas. Chemical Exchange Saturation Transfer imaging of glutamate (gluCEST) is a recently developed imaging technique that can map glutamate distribution in the entire brain with higher sensitivity and at higher resolution than previous techniques. It thus has strong potential clinical applications to assess glutamate changes in the brain. High field is a key condition to perform gluCEST images with a meaningful signal to noise ratio. Thus, even if some studies started to evaluate gluCEST in humans, most studies focused on rodent models that can be imaged at high magnetic field. In particular, systematic characterization of gluCEST contrast distribution throughout the whole brain has never been performed in humans or non-human primates. Here, we characterized for the first time the distribution of the glutamate index in the whole brain and in large-scale networks of mouse lemur primates at 11.7 Tesla. Because of its small size, this primate can be imaged in high magnetic field systems. It is widely studied as a model of cerebral aging or Alzheimer's disease. We observed high gluCEST contrast in cerebral regions such as the nucleus accumbens, septum, basal forebrain, cortical areas 24 and 25. Age-related alterations of this biomarker were detected in the nucleus accumbens, septum, basal forebrain, globus pallidus, hypophysis, cortical areas 24, 21, 6 and in olfactory bulbs. An age-related gluCEST contrast decrease was also detected in specific neuronal networks, such as fronto-temporal and evaluative limbic networks. These results outline regional differences of gluCEST contrast and strengthen its potential to provide new biomarkers of cerebral function in primates.

scholarly journals Whole-Brain Monosynaptic Afferent Inputs to Basal Forebrain Cholinergic System

2016 ◽  
Vol 10 ◽  
Author(s):  
Rongfeng Hu ◽  
Sen Jin ◽  
Xiaobin He ◽  
Fuqiang Xu ◽  
Ji Hu
Keyword(s):  
Basal Forebrain ◽  
Cholinergic System ◽  
Whole Brain ◽  
Afferent Inputs

scholarly journals The basal forebrain cholinergic system in aging and dementia. Rescuing cholinergic neurons from neurotoxic amyloid-β42 with memantine

2011 ◽  
Vol 221 (2) ◽  
pp. 594-603 ◽  
Author(s):  
Csaba Nyakas ◽  
Ivica Granic ◽  
László G. Halmy ◽  
Pradeep Banerjee ◽  
Paul G.M. Luiten
Keyword(s):  
Basal Forebrain ◽  
Cholinergic System ◽  
Cholinergic Neurons

scholarly journals Cholinergic System and NGF Receptors: Insights from the Brain of the Short-Lived Fish Nothobranchius furzeri

2020 ◽  
Vol 10 (6) ◽  
pp. 394
Author(s):  
Paolo de Girolamo ◽  
Adele Leggieri ◽  
Antonio Palladino ◽  
Carla Lucini ◽  
Chiara Attanasio ◽  
...  
Keyword(s):  
Cholinergic System ◽  
Preoptic Area ◽  
Cholinergic Neurons ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Neuronal Populations ◽  
Dependent Change ◽  
Nothobranchius Furzeri ◽  
Age Dependent ◽  
The Brain

Nerve growth factor (NGF) receptors are evolutionary conserved molecules, and in mammals are considered necessary for ensuring the survival of cholinergic neurons. The age-dependent regulation of NTRK1/NTRKA and p75/NGFR in mammalian brain results in a reduced response of the cholinergic neurons to neurotrophic factors and is thought to play a role in the pathogenesis of neurodegenerative diseases. Here, we study the age-dependent expression of NGF receptors (NTRK1/NTRKA and p75/NGFR) in the brain of the short-lived teleost fish Nothobranchius furzeri. We observed that NTRK1/NTRKA is more expressed than p75/NGFR in young and old animals, although both receptors do not show a significant age-dependent change. We then study the neuroanatomical organization of the cholinergic system, observing that cholinergic fibers project over the entire neuroaxis while cholinergic neurons appear restricted to few nuclei situated in the equivalent of mammalian subpallium, preoptic area and rostral reticular formation. Finally, our experiments do not confirm that NTRK1/NTRKA and p75/NGFR are expressed in cholinergic neuronal populations in the adult brain of N. furzeri. To our knowledge, this is the first study where NGF receptors have been analyzed in relation to the cholinergic system in a fish species along with their age-dependent modulation. We observed differences between mammals and fish, which make the African turquoise killifish an attractive model to further investigate the fish specific NGF receptors regulation.

Amyloid-β, tau, and the cholinergic system in Alzheimer’s disease: seeking direction in a tangle of clues

2020 ◽  
Vol 31 (4) ◽  
pp. 391-413 ◽  
Author(s):  
Alireza Majdi ◽  
Saeed Sadigh-Eteghad ◽  
Sepideh Rahigh Aghsan ◽  
Fereshteh Farajdokht ◽  
Seyed Mehdi Vatandoust ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Basal Forebrain ◽  
Cholinergic System ◽  
Amyloid Β ◽  
Cholinergic Neurons ◽  
Clinical Findings ◽  
App Metabolism ◽  
Main Culprit

AbstractThe link between histopathological hallmarks of Alzheimer’s disease (AD), i.e. amyloid plaques, and neurofibrillary tangles, and AD-associated cognitive impairment, has long been established. However, the introduction of interactions between amyloid-beta (Aβ) as well as hyperphosphorylated tau, and the cholinergic system to the territory of descriptive neuropathology has drastically changed this field by adding the theory of synaptic neurotransmission to the toxic pas de deux in AD. Accumulating data show that a multitarget approach involving all amyloid, tau, and cholinergic hypotheses could better explain the evolution of events happening in AD. Various species of both Aβ and tau could be traced in cholinergic neurons of the basal forebrain system early in the course of the disease. These molecules induce degeneration in the neurons of this system. Reciprocally, aberrant cholinergic system modulation promotes changes in amyloid precursor protein (APP) metabolism and tau phosphorylation, resulting in neurotoxicity, neuroinflammation, and neuronal death. Altogether, these changes may better correlate with the clinical findings and cognitive impairment detected in AD patients. Failure of several of Aβ- and tau-related therapies further highlights the need for special attention to molecules that target all of these mentioned pathologic changes. Another noteworthy fact here is that none of the popular hypotheses of AD such as amyloidopathy or tauopathy seem to be responsible for the changes observed in AD alone. Thus, the main culprit should be sought higher in the stream somewhere in APP metabolism or Wnt signaling in the cholinergic system of the basal forebrain. Future studies should target these pathological events.

scholarly journals Fluoxetine and Ketamine Reverse the Depressive but Not Anxiety Behavior Induced by Lesion of Cholinergic Neurons in the Horizontal Limb of the Diagonal Band of Broca in Male Rat

2021 ◽  
Vol 15 ◽  
Author(s):  
Linghong Chen ◽  
Yuting Ke ◽  
Hong Ma ◽  
Lei Gao ◽  
Yiying Zhou ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Basal Forebrain ◽  
Cholinergic System ◽  
Forced Swimming Test ◽  
Sucrose Solution ◽  
Cholinergic Neurons ◽  
Diagonal Band ◽  
Immobility Time ◽  
Swimming Test ◽  
Diagonal Band Of Broca

The basal forebrain cholinergic system is involved in cognitive processes, but the role of the basal forebrain cholinergic system in depression is unknown. We investigated whether a lesion of cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) produces depressive-like behavior and whether fluoxetine or ketamine inhibits such depressive-like behaviors. Here, in rats, we used 192 IgG-saporin to eliminate the cholinergic neurons of the HDB and evaluated depressive-like behaviors using a preference test for sucrose solution and the forced swimming test. Fourteen days after the injection of 192 IgG-saporin into the HDB, the rats exhibited a significantly fewer number of choline acetyltransferase positive cell density in HDB, accompanied with neuronal loss in the entire hippocampus. Meanwhile, these rats significantly reduced preference for sucrose solution, increased immobility time in the forced swimming test, reduced locomotor activity, decreased context dependent memory in fear conditioning and the time spent in the open arms of the plus-maze. A single dose of ketamine (10 mg/kg) increased the sucrose solution consumption, reduced the immobility time in the forced swim test (FST), and increased locomotor activity compared to vehicle-treated rats. Moreover, in rats that were continuously treated with fluoxetine (10 mg/kg/day for 11 days), the sucrose solution consumption increased, the immobility time in the FST decreased, and locomotor activity increased compared to vehicle-treated rats. The present results demonstrate that a lesion of HDB cholinergic neurons results in depressive-like and anxiety-like behaviors and that antidepressants such as fluoxetine or ketamine, can reverse these depressive-like behaviors but not anxiety-like behaviors, and suggest that a lesion of HDB cholinergic neurons and followed hippocampus damage may be involved in the pathogenesis of depression.

scholarly journals Complete morphologies of basal forebrain cholinergic neurons in the mouse

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Hao Wu ◽  
John Williams ◽  
Jeremy Nathans
Keyword(s):  
Basal Forebrain ◽  
Cholinergic System ◽  
Vascular Tone ◽  
Neuronal Excitability ◽  
Cholinergic Neurons ◽  
Symptomatic Therapy ◽  
Branch Points ◽  
Basal Forebrain Cholinergic Neurons ◽  
Sparse Labeling ◽  
Cholinergic Signaling

The basal forebrain cholinergic system modulates neuronal excitability and vascular tone throughout the cerebral cortex and hippocampus. This system is severely affected in Alzheimer's disease (AD), and drug treatment to enhance cholinergic signaling is widely used as symptomatic therapy in AD. Defining the full morphologies of individual basal forebrain cholinergic neurons has, until now, been technically beyond reach due to their large axon arbor sizes. Using genetically-directed sparse labeling, we have characterized the complete morphologies of basal forebrain cholinergic neurons in the mouse. Individual arbors were observed to span multiple cortical columns, and to have >1000 branch points and total axon lengths up to 50 cm. In an AD model, cholinergic axons were slowly lost and there was an accumulation of axon-derived material in discrete puncta. Calculations based on published morphometric data indicate that basal forebrain cholinergic neurons in humans have a mean axon length of ∼100 meters.

Deletion of p75NTR enhances the cholinergic innervation pattern of the visual cortex

2016 ◽  
Vol 33 ◽  
Author(s):  
VIOLA VON BOHLEN UND HALBACH ◽  
OLIVER VON BOHLEN UND HALBACH
Keyword(s):  
Visual Cortex ◽  
Basal Forebrain ◽  
Cholinergic System ◽  
Cortical Plasticity ◽  
Cholinergic Neurons ◽  
Cholinergic Innervation ◽  
Neurotrophin Receptor ◽  
Innervation Pattern ◽  
Layer V ◽  
Deficient Mice

AbstractThe cholinergic system is involved in cortical plasticity, attention, and learning. Within the visual cortex the cholinergic system seems to play a role in visual perception. The cholinergic neurons which project into the visual cortex are located in the basal forebrain. It has been shown that mice deficient for the low-affinity neurotrophin receptor p75NTR display increased numbers of cholinergic neurons in the basal forebrain and a denser cholinergic innervation of the hippocampus. This prompted us to analyze whether the cholinergic system is altered in adult p75NTR deficient mice. By analyzing the densities of cholinergic fibers within layer IV as well as within layer V of the visual cortex, we found that adult p75NTR deficient mice display increased cholinergic fiber densities. However, this increase was not accompanied by an increase in the density of local cholinergic neurons within the visual cortex. This indicates that the enhanced cholinergic innervation of the visual cortex is due to alteration of the cholinergic neurons located in the basal forebrain, projecting to the visual cortex. The increased cholinergic innervation of the visual cortex makes the p75NTR deficient mice an attractive model to study the necessity of the cholinergic system for the visual cortex.

The Cholinergic Multicompartmental Basal Forebrain Microcircuit

2017 ◽  
pp. 163-184
Author(s):  
Laszlo Zaborszky ◽  
Peter Gombkoto
Keyword(s):  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Medial Septum ◽  
Cortical Activation ◽  
Ach Release ◽  
Diagonal Band ◽  
Substantia Innominata ◽  
Arousal Effect ◽  
Hippocampal Complex ◽  
The Brain

The basal forebrain (BF) is composed of an affiliation of structures, including the medial septum, ventral pallidum (VP), vertical diagonal band (VDB) and horizontal diagonal band (HDB) nuclei, substantia innominata/extended amygdala (SI/EA), and peripallidal regions. Together, they constitute one of the most extensive multicompartmental microcircuits in the brain. A prominent feature of the mammalian BF is the presence of aggregated and nonaggregated, large, cholinergic neurons, which project to the cerebral cortex, the hippocampal complex, and the amygdala. This highly complex system has been implicated in cortical activation, attention, motivation, and memory, as well as neuropsychiatric disorders such as Alzheimer’s disease, Parkinson’s disease, schizophrenia, and drug abuse. Advances in modern tracing, genetic, and refined pharmacological techniques have dramatically increased the understanding of how the BF cholinergic system can support both phasic acetylcholine (ACh) release in attention, memory, and sensory processing and tonic ACh release over broad cortical areas as part of a general arousal effect.

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