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Basal Forebrain

Rongfeng Hu, Sen Jin, Xiaobin He, Fuqiang Xu, Ji Hu
The basal forebrain cholinergic system (BFCS) robustly modulates many important behaviors, such as arousal, attention, learning and memory, through heavy projections to cortex and hippocampus. However, the presynaptic partners governing BFCS activity still remain poorly understood. Here, we utilized a recently developed rabies virus-based cell-type-specific retrograde tracing system to map the whole-brain afferent inputs of the BFCS. We found that the BFCS receives inputs from multiple cortical areas, such as orbital frontal cortex, motor cortex, and insular cortex, and that the BFCS also receives dense inputs from several subcortical nuclei related to motivation and stress, including lateral septum, central amygdala, paraventricular nucleus of hypothalamus, dorsal raphe, and parabrachial nucleus...
2016: Frontiers in Neuroanatomy
G Kaur, M Pawlik, S E Gandy, M E Ehrlich, J F Smiley, E Levy
Recent data suggest that intraneuronal accumulation of metabolites of the amyloid-β-precursor protein (APP) is neurotoxic. We observed that transgenic mice overexpressing in neurons a human APP gene harboring the APP(E693Q) (Dutch) mutation have intraneuronal lysosomal accumulation of APP carboxylterminal fragments (APP-CTFs) and oligomeric amyloid β (oAβ) but no histological evidence of amyloid deposition. Morphometric quantification using the lysosomal marker protein 2 (LAMP-2) immunolabeling showed higher neuronal lysosomal counts in brain of 12-months-old APP(E693Q) as compared with age-matched non-transgenic littermates, and western blots showed increased lysosomal proteins including LAMP-2, cathepsin D and LC3...
October 25, 2016: Molecular Psychiatry
Johnny Phong Do, Min Xu, Seung-Hee Lee, Wei-Cheng Chang, Siyu Zhang, Shinjae Chung, Tyler J Yung, Jiang Lan Fan, Kazunari Miyamichi, Liqun Luo, Yang Dan
No abstract text is available yet for this article.
October 24, 2016: ELife
Marion T Turnbull, Elizabeth J Coulson
Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and are a major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in sporadic AD are unknown. Here we investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or a resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation...
October 20, 2016: Journal of Alzheimer's Disease: JAD
Min-Soo Kim, Ji Hye Bang, Jun Lee, Jung-Soo Han, Tae Gon Baik, Won Kyung Jeon
BACKGROUND: Ginkgo biloba extract (GBE)-a widely used nutraceutical-is reported to have diverse functions, including positive effects on memory and vasodilatory properties. Although numerous studies have assessed the neuroprotective properties of GBE in ischemia, only a few studies have investigated the neuro-pharmacological mechanisms of action of GBE in chronic cerebral hypoperfusion (CCH). PURPOSE: In the present study, we sought to determine the effects of GBE on CCH-induced neuroinflammation and cholinergic dysfunction in a rat model of bilateral common carotid artery occlusion (BCCAo)...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Christopher S Medina, Octavian Biris, Tomas L Falzone, Xiaowei Zhang, Amber J Zimmerman, Elaine L Bearer
Microtubule-based motors carry cargo back and forth between the synaptic region and the cell body. Defects in axonal transport result in peripheral neuropathies, some of which are caused by mutations in KIF5A, a gene encoding one of the heavy chain isoforms of conventional kinesin-1. Some mutations in KIF5A also cause severe central nervous system defects in humans. While transport dynamics in the peripheral nervous system have been well characterized experimentally, transport in the central nervous system is less experimentally accessible and until now not well described...
October 14, 2016: NeuroImage
Meg Waraczynski, Samantha Abbott, Alex V Schultz
Previous work in our laboratory has shown that stimulating D2 dopamine receptors in the central sublenticular extended amygdala (SLEAc) can render medial forebrain bundle (MFB) stimulation less rewarding. One of the many ways in which D2 stimulation could affect the activity status of SLEAc neurons is by indirectly blocking calcium ion (Ca(2+)) influx through CaV1.3 channels. He we directly investigate the effects of blocking CaV1.3 channels on the rewarding effect of MFB stimulation. In experiment one, CaV1...
October 13, 2016: Behavioural Brain Research
Paula Moyano, Javier Del Pino, María José Anadon, María Jesús Díaz, Gloria Gómez, María Teresa Frejo
Chlorpyrifos (CPF) is an organophosphate insecticide reported to induce, both after acute and repeated exposure, learning and memory dysfunctions, although the mechanism is not completely known. CPF produces basal forebrain cholinergic neuronal loss, involved on learning and memory regulation, which could be the cause of such cognitive disorders. This effect was reported to be induced through apoptotic process, partially mediated by AChE overexpression, although neuronal necrosis was also described after CPF exposure...
October 10, 2016: Neurotoxicology and Teratology
Shanni N Silberberg, Leila Taher, Susan Lindtner, Magnus Sandberg, Alex S Nord, Daniel Vogt, Gabriel L Mckinsey, Renee Hoch, Kartik Pattabiraman, Dongji Zhang, Jose L Ferran, Aleksandar Rajkovic, Olga Golonzhka, Carol Kim, Hongkui Zeng, Luis Puelles, Axel Visel, John L R Rubenstein
Elucidating the transcriptional circuitry controlling forebrain development requires an understanding of enhancer activity and regulation. We generated stable transgenic mouse lines that express CreER(T2) and GFP from ten different enhancer elements with activity in distinct domains within the embryonic basal ganglia. We used these unique tools to generate a comprehensive regional fate map of the mouse subpallium, including sources for specific subtypes of amygdala neurons. We then focused on deciphering transcriptional mechanisms that control enhancer activity...
October 5, 2016: Neuron
Marlene A Wilson, Jim R Fadel
Cholinergic activation regulates cognitive function, particularly long-term memory consolidation. This Review presents an overview of the anatomical, neurochemical, and pharmacological evidence supporting the cholinergic regulation of Pavlovian contextual and cue-conditioned fear learning and extinction. Basal forebrain cholinergic neurons provide inputs to neocortical regions and subcortical limbic structures such as the hippocampus and amygdala. Pharmacological manipulations of muscarinic and nicotinic receptors support the role of cholinergic processes in the amygdala, hippocampus, and prefrontal cortex in modulating the learning and extinction of contexts or cues associated with threat...
October 5, 2016: Journal of Neuroscience Research
Alexander M Herman, Joshua Ortiz-Guzman, Mikhail Kochukov, Isabella Herman, Kathleen B Quast, Jay M Patel, Burak Tepe, Jeffrey C Carlson, Kevin Ung, Jennifer Selever, Qingchun Tong, Benjamin R Arenkiel
Atypical food intake is a primary cause of obesity and other eating and metabolic disorders. Insight into the neural control of feeding has previously focused mainly on signalling mechanisms associated with the hypothalamus, the major centre in the brain that regulates body weight homeostasis. However, roles of non-canonical central nervous system signalling mechanisms in regulating feeding behaviour have been largely uncharacterized. Acetylcholine has long been proposed to influence feeding owing in part to the functional similarity between acetylcholine and nicotine, a known appetite suppressant...
October 3, 2016: Nature
Asante R Kamkwalala, Paul A Newhouse
The major components of the cholinergic receptor system of the human brain include projections from the basal forebrain nuclei, and utilize the two types of receptors that they synapse on, nicotinic and muscarinic acetylcholine receptors. With the widespread cortical and subcortical projections of the basal forebrain, activity of these two receptor systems provide modulation of neurotransmitter activity underlying normal cognitive processes, such as attention, episodic memory, and working memory. Alzheimer's disease (AD) targets and damages cholinergic neurons in the basal forebrain, and as these projections are lost, cognitive performance progressively declines...
September 30, 2016: Current Alzheimer Research
Y A Sidorova, M Saarma
Four glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) have been characterized: GDNF, neurturin (NRTN), artemin (ARTN) and persephin (PSPN). These proteins support and restore multiple neuronal populations such as dopaminergic, sensory, motor, hippocampal, basal forebrain, enteric, sympathetic and parasympathetic neurons. Therefore, GFLs attracted significant attention as a potential cure for the diseases caused by neuronal injury and degeneration. Results of multiple experiments indicate that GFLs can alleviate behavioral symptoms and restore affected neurons in animal models of several neurological disorders including, among others, Parkinson's disease (PD)...
July 2016: Molekuliarnaia Biologiia
Sung Ho Jang, Jeong Pyo Seo
BACKGROUND: We report on a patient who appeared to show recovery of an injured anterior cingulum via an aberrant neural tract between an injured cingulum and the basalis nucleus of Meynert following traumatic brain injury (TBI), which was demonstrated on diffusion tensor tractography (DTT). METHODS: A 47-year-old male who had suffered a pedestrian traffic accident underwent conservative management for diffuse traumatic axonal injury. When starting rehabilitation at 6 weeks after onset, evaluation using the Mini-Mental State Examination (MMSE) could not be performed due to the severity of his cognitive dysfunction...
September 2016: Medicine (Baltimore)
Jenne M Westberry, Michael Meredith
Chemosensory stimuli from same species (conspecific) and different species (heterospecific) elicit categorically different immediate-early gene (IEG) response patterns in medial amygdala in male hamsters and mice. All heterospecific stimuli activate anterior medial amygdala (MeA) but only especially salient heterospecific stimuli, such as those from predators activate posterior medial amygdala (MeP). We previously reported that characteristic patterns of response in separate populations of cells in MeA and MeP distinguish between different conspecific stimuli...
September 20, 2016: Chemical Senses
Johnny Phong Do, Min Xu, Seung-Hee Lee, Wei-Cheng Chang, Siyu Zhang, Shinjae Chung, Tyler J Yung, Jiang Lan Fan, Kazunari Miyamichi, Liqun Luo, Yang Dan
The basal forebrain (BF) plays key roles in multiple brain functions, including sleep-wake regulation, attention, and learning/memory, but the long-range connections mediating these functions remain poorly characterized. Here we performed whole-brain mapping of both inputs and outputs of four BF cell types - cholinergic, glutamatergic, and parvalbumin-positive (PV+) and somatostatin-positive (SOM+) GABAergic neurons - in the mouse brain. Using rabies virus -mediated monosynaptic retrograde tracing to label the inputs and adeno-associated virus to trace axonal projections, we identified numerous brain areas connected to the BF...
2016: ELife
Vania F Prado, Helena Janickova, Mohammed A Al-Onaizi, Marco A M Prado
Cognitive flexibility, the ability to adjust behavior in response to new and unexpected conditions in the environment, is essential for adaptation to new challenges and survival. The cholinergic system is an important modulator of this complex behavior however, the exact cholinergic circuits involved in this modulation and the precise influence of acetylcholine (ACh) in the process is still not fully understood. Here we review the role of different cholinergic circuits in cognitive flexibility. Strong evidence indicates that cholinergic interneurons (CINs) from the dorsomedial striatum are essential for facilitating the establishment of a new selected strategy; an effect that seems to depend mainly on activation of muscarinic receptors...
September 15, 2016: Neuroscience
Xin Wang, Aiguo Chen, Honghai Wu, Min Ye, Hong Cheng, Xinfeng Jiang, Xiaohong Wang, Xiaobin Zhang, Di Wu, Xin Gu, Feiyang Shen, Chunlei Shan, Duonan Yu
Post-stroke cognitive impairment (PSCI), commonly seen in the clinical practice, is a major factor impeding patient rehabilitation. Enriched environment (EE) intervention is a simple and effective way to improve cognitive impairment, partially due to the rebalancing of the basal forebrain-hippocampus cholinergic signaling pathway. Epigenetic changes have been identified in many cognitive disorders. However, studies on the effects of EE on epigenetic regulation of cholinergic circuits in PSCI animal models have not yet been reported...
November 1, 2016: Brain Research
Olena Santangeli, Henna Lehtikuja, Eeva Palomäki, Henna-Kaisa Wigren, Tiina Paunio, Tarja Porkka-Heiskanen
STUDY OBJECTIVE: Adverse early-life events induce behavioral psychopathologies and sleep changes in adulthood. In order to understand the molecular level mechanisms by which the maltreatment modifies sleep, valid animal models are needed. Changing pups between mothers at early age (cross-fostering) may satisfyingly model adverse events in human childhood. METHODS: Cross-fostering (CF) was used to model mild early-life stress in male and female Wistar rats. Behavior and BDNF gene expression in the basal forebrain (BF), cortex, and hypothalamus were assessed during adolescence and adulthood...
September 9, 2016: Sleep
Susana S Correia, Ki A Goosens
Reward and punishment are often thought of as opposing processes: rewards and the environmental cues that predict them elicit approach and consummatory behaviors, while punishments drive aversion and avoidance behaviors. This framework suggests that there may be segregated brain circuits for these valenced behaviors. The basolateral amygdala (BLA) is one brain region that contributes to both types of motivated behavior. Individual neurons in the BLA can favor positive over negative valence, or vice versa, but these neurons are intermingled, showing no anatomical segregation...
October 2016: Learning & Memory
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