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Basal Forebrain

Noriomi Eguchi, Ichiro Sora, Keiko Muguruma
Human brain development has generally been studied through the analysis of postmortem tissues because of limited access to fetal brain tissues. This approach, however, only provides information from the perspective of long-term development. To investigate the pathophysiology of neurodevelopmental disorders, it is necessary to understand the detailed mechanisms of human brain development. Recent advances in pluripotent stem cell (PSC) technologies enable us to establish in vitro brain models from human induced PSCs (hiPSCs), which can be used to examine the pathophysiological mechanisms of neurodevelopmental disorders...
March 7, 2018: Biochemical and Biophysical Research Communications
Marion T Turnbull, Zoran Boskovic, Elizabeth J Coulson
Degeneration of basal forebrain cholinergic neurons (BFCNs) precedes hippocampal degeneration and pathological amyloid-beta (Aβ) accumulation, and underpins the development of cognitive dysfunction in sporadic Alzheimer's disease (AD). We hypothesized that degeneration of BFCNs causes a decrease in neurotrophin levels in innervated brain areas, which in turn promotes the development of Aβ pathology and cognitive impairment. Here we show that lesion of septo-hippocampal BFCNs in a pre-symptomatic transgenic amyloid AD mouse model (APP/PS1 mice) increases soluble Aβ levels in the hippocampus, and induces cognitive deficits in a spatial memory task that are not seen in either unlesioned APP/PS1 or non-transgenic littermate control mice...
2018: Frontiers in Molecular Neuroscience
Darwin O Larco, Bradly M Bauman, Madelaine Cho-Clark, Shaila K Mani, T John Wu
Gonadotropin-releasing hormone (GnRH) neurons originate outside the central nervous system (CNS) in the nasal placode where their migration to the basal forebrain is dependent on the integration of multiple signaling cues during development. The proper migration and establishment of the GnRH neuronal population within the CNS are critical for normal pubertal onset and reproductive function. The endopeptidase EP24.15 is expressed along the migratory path of GnRH neurons and cleaves the full-length GnRH to generate the metabolite GnRH-(1-5)...
2018: Frontiers in Endocrinology
Pamela Jarrett, Alexander Easton, Kenneth Rockwood, Sarah Dyack, Alexander McCollum, Victoria Siu, Seyed M Mirsattari, Andreu Massot-Tarrús, M Jill Beis, Nolan D'Souza, Sultan Darvesh
OBJECTIVE: Neuronal ceroid-lipofuscinoses are a heterogeneous group of inherited disorders in which abnormal lipopigments form lysosomal inclusion bodies in neurons. Kufs disease is rare, and clinical symptoms include seizures, progressive cognitive impairment, and myoclonus. Most cases of Kufs disease are autosomal recessive; however, there have been a few case reports of an autosomal dominant form linked to mutations within the DNAJC5 gene. METHODS: We describe a family with Kufs disease in which the proband and three of her four children presented with cognitive impairment, seizures, and myoclonus...
March 2018: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
Gunes Unal, Michael G Crump, Tim J Viney, Tímea Éltes, Linda Katona, Thomas Klausberger, Peter Somogyi
Medial septal GABAergic neurons of the basal forebrain innervate the hippocampus and related cortical areas, contributing to the coordination of network activity, such as theta oscillations and sharp wave-ripple events, via a preferential innervation of GABAergic interneurons. Individual medial septal neurons display diverse activity patterns, which may be related to their termination in different cortical areas and/or to the different types of innervated interneurons. To test these hypotheses, we extracellularly recorded and juxtacellularly labeled single medial septal neurons in anesthetized rats in vivo during hippocampal theta and ripple oscillations, traced their axons to distant cortical target areas, and analyzed their postsynaptic interneurons...
March 3, 2018: Brain Structure & Function
Tracy Butler, Patrick Harvey, Anup Deshpande, Emily Tanzi, Yi Li, Wai Tsui, Caroline Silver, Esther Fischer, Xiuyuan Wang, Jingyun Chen, Henry Rusinek, Elizabeth Pirraglia, Ricardo S Osorio, Lidia Glodzik, Mony J de Leon
Alzheimer's disease (AD) is known to be associated with loss of cholinergic neurons in the nucleus basalis of Meynert, located in the posterior basal forebrain. Structural changes of septal nuclei, located in the anterior basal forebrain, have not been well studied in AD. Using a validated algorithm, we manually traced septal nuclei on high-resolution coronal magnetic resonance imaging (MRI) in 40 subjects with mild cognitive impairment (MCI) or AD, 89 healthy controls, and 18 subjects who were cognitively normal at the time of MRI but went on to develop AD an average of 2...
February 2, 2018: Neurobiology of Aging
Kouko Tatsumi, Ayami Isonishi, Miwako Yamasaki, Yoshie Kawabe, Shoko Morita-Takemura, Kazuki Nakahara, Yuki Terada, Takeaki Shinjo, Hiroaki Okuda, Tatsuhide Tanaka, Akio Wanaka
Astrocytes are the most abundant glia cell type in the central nervous system (CNS), and are known to constitute heterogeneous populations that differ in their morphology, gene expression and function. Although glial fibrillary acidic protein (GFAP) is the cardinal cytological marker of CNS astrocytes, GFAP-negative astrocytes can easily be found in the adult CNS. Astrocytes are also allocated to spatially distinct regional domains during development. This regional heterogeneity suggests that they help to coordinate post-natal neural circuit formation and thereby to regulate eventual neuronal activity...
2018: Frontiers in Neuroanatomy
Ross D Markello, R Nathan Spreng, Wen-Ming Luh, Adam K Anderson, Eve De Rosa
The basal forebrain (BF) is poised to play an important neuromodulatory role in brain regions important to cognition due to its broad projections and complex neurochemistry. While significant in vivo work has been done to elaborate BF function in nonhuman rodents and primates, comparatively limited work has examined the in vivo function of the human BF. In the current study we used multi-echo resting state functional magnetic resonance imaging (rs-fMRI) from 100 young adults (18-34 years) to assess the potential segregation of human BF nuclei as well as their associated projections...
February 26, 2018: NeuroImage
Cindy F Yang, Jack L Feldman
The preBötzinger complex (preBötC), a compact medullary region essential for generating normal breathing rhythm and pattern, is the kernel of the breathing central pattern generator (CPG). Excitatory preBötC neurons in rats project to major breathing-related brainstem regions. Here, we provide a brainstem connectivity map in mice for both excitatory and inhibitory preBötC neurons. Using a genetic strategy to label preBötC neurons, we confirmed extensive projections of preBötC excitatory neurons within the brainstem breathing CPG including the contralateral preBötC, Bötzinger Complex (BötC), ventral respiratory group (VRG), nucleus of the solitary tract (NTS), parahypoglossal nucleus, parafacial region (RTN/pFRG or alternatively, pFL /pFV ), parabrachial and Kölliker-Füse nuclei, as well as major projections to the midbrain periaqueductal gray (PAG)...
February 23, 2018: Journal of Comparative Neurology
Kathrin Müsch, Christopher J Honey
In this issue of Neuron, Turchi et al. (2018) reversibly inactivate the basal forebrain to show that this region magnifies global neocortical signal fluctuations without altering the topography of canonical resting-state networks. Thus, spatially diffuse signals measurable via functional neuroimaging may track large-scale neuromodulatory state changes in the primate brain.
February 21, 2018: Neuron
Doug M Boyer, Arianna R Harrington
Supplying the central nervous system with oxygen and glucose for metabolic activities is a critical function for all animals at physiologic, anatomical, and behavioral levels. A relatively proximate challenge to nourishing the brain is maintaining adequate blood flow. Euarchontans (primates, dermopterans and treeshrews) display a diversity of solutions to this challenge. Although the vertebral artery is a major encephalic vessel, previous research has questioned its importance for irrigating the cerebrum. This presents a puzzling scenario for certain strepsirrhine primates (non-cheirogaleid lemuriforms) that have reduced promontorial branches of the internal carotid artery and no apparent alternative encephalic vascular route except for the vertebral artery...
January 2018: Journal of Human Evolution
Joseph Therriault, Kok Pin Ng, Tharick A Pascoal, Sulantha Mathotaarachchi, Min Su Kang, Hanne Struyfs, Monica Shin, Andrea L Benedet, Ishan C Walpola, Vasavan Nair, Serge Gauthier, Pedro Rosa-Neto
OBJECTIVE: To identify the pathophysiologic mechanisms and clinical significance of anosognosia for cognitive decline in mild cognitive impairment. METHODS: We stratified 468 patients with amnestic mild cognitive impairment into intact and impaired awareness groups, determined by the discrepancy between the patient and the informant score on the Everyday Cognition questionnaire. Voxel-based linear regression models evaluated the associations between self-awareness status and baseline β-amyloid load, measured by [ 18 F]florbetapir, and the relationships between awareness status and regional brain glucose metabolism measured by [ 18 F]fluorodeoxyglucose at baseline and at 24-month follow-up...
February 14, 2018: Neurology
Myrto Denaxa, Guilherme Neves, Adam Rabinowitz, Sarah Kemlo, Petros Liodis, Juan Burrone, Vassilis Pachnis
Cortical networks are composed of excitatory projection neurons and inhibitory interneurons. Finding the right balance between the two is important for controlling overall cortical excitation and network dynamics. However, it is unclear how the correct number of cortical interneurons (CIs) is established in the mammalian forebrain. CIs are generated in excess from basal forebrain progenitors, and their final numbers are adjusted via an intrinsically determined program of apoptosis that takes place during an early postnatal window...
February 13, 2018: Cell Reports
Georgina A Lean, Yong-Jun Liu, David C Lyon
The basal forebrain provides cholinergic inputs to primary visual cortex (V1) that play a key modulatory role on visual function. While basal forebrain afferents terminate in the infragranular layers of V1, acetylcholine is delivered to more superficial layers through volume transmission. Nevertheless, direct synaptic contact in deep layers 5 and 6 may provide a more immediate effect on V1 modulation. Using helper viruses with cell type specific promoters to target retrograde infection of pseudotyped and genetically modified rabies virus evidence was found for direct synaptic input onto V1 inhibitory neurons...
February 14, 2018: Journal of Comparative Neurology
Jun-Cheng Weng, Yu-Syuan Chou, Guo-Joe Huang, Yeu-Sheng Tyan, Ming-Chou Ho
RATIONALE: The World Health Organization regards betel quid (BQ) as a human carcinogen, and DSM-IV and ICD-10 dependence symptoms may develop with its heavy use. BQ's possible effects of an enhanced reward system and disrupted inhibitory control may increase the likelihood of habitual substance use. OBJECTIVES: The current study aimed to employ resting-state fMRI to examine the hypothesized enhanced reward system (e.g., the basal forebrain system) and disrupted inhibitory control (e...
February 13, 2018: Psychopharmacology
Chantalle Briggs, Michiru Hirasawa, Kazue Semba
Glutamate transporter 1 (GLT1) is the main astrocytic transporter that shapes glutamatergic transmission in the brain. However, whether this transporter modulates sleep/wake regulatory neurons is unknown. Using quantitative immunohistochemical analysis, we assessed perisomatic GLT1 apposition with sleep/wake neurons in the male rat following 6-h sleep deprivation (SD) or following 6-h undisturbed conditions when animals were mostly asleep (Rest). We found that SD decreased perisomatic GLT1 apposition with wake-promoting orexin (ORX) neurons in the lateral hypothalamus (LH) compared to Rest...
February 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Koji Kasanuki, Tanis J Ferman, Melissa E Murray, Michael G Heckman, Otto Pedraza, Fadi S Hanna Al-Shaikh, Takayasu Mishima, Nancy N Diehl, Jay A van Gerpen, Ryan J Uitti, Zbigniew K Wszolek, Neill R Graff-Radford, Dennis W Dickson
INTRODUCTION: Excessive daytime sleepiness is a commonly reported clinical feature of dementia with Lewy bodies (DLB) that can occur early in the disease. Cholinergic depletion is known to be severe in DLB, even when dementia severity is mild. The nucleus basalis of Meynert serves as a primary source of cortical acetylcholine, and has a role in facilitating cortical activation and arousal. We sought to determine whether daytime sleepiness at the initial evaluation of patients with DLB was associated with neuronal loss in the nucleus basalis of Meynert...
February 3, 2018: Parkinsonism & related Disorders
Irene Chaves-Coira, Margarita L Rodrigo-Angulo, Angel Nuñez
Sensory processing in the cortex should integrate inputs arriving from receptive fields located on both sides of the body. This role could be played by the corpus callosum through precise projections between both hemispheres. However, different studies suggest that cholinergic projections from the basal forebrain (BF) could also contribute to the synchronization and integration of cortical activities. Using tracer injections and optogenetic techniques in transgenic mice, we investigated whether the BF cells project bilaterally to sensory cortical areas, and have provided anatomical evidence to support a modulatory role for the cholinergic projections in sensory integration...
2018: Frontiers in Neuroanatomy
Alexandre Alié, Lucie Devos, Jorge Torres-Paz, Lise Prunier, Fanny Boulet, Maryline Blin, Yannick Elipot, Sylvie Retaux
The fish Astyanax mexicanus comes in two forms: the normal surface-dwelling and the blind depigmented cave-adapted morphs. Comparing the development of their basal forebrain, we found quantitative differences in numbers of cells in specific clusters for six out of nine studied neuropeptidergic cell types. Investigating the origins of these differences, we showed that early Shh and Fgf signaling impact on the development of NPY and Hypocretin clusters, via effect on Lhx7 and Lhx9 transcription factors, respectively...
February 6, 2018: ELife
Hiroaki Ishida, Ken-Ichi Inoue, Masahiko Takada
The amygdala codes the visual-gustatory/somatosensory valence for feeding behavior. On the other hand, the ventral premotor cortex (PMv) plays a central role in reaching and grasping movements prerequisite for feeding behavior. This implies that object valence signals derived from the amygdala may be crucial for feeding-related motor actions exerted by PMv. However, since no direct connectivity between the amygdala and PMv has been reported, the structural basis of their functional interactions still remains elusive...
2018: Frontiers in Neuroanatomy
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