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Cholinergic interneurons

Christoph Straub, Jessica Lizette Saulnier, Aurelien Bègue, Danielle D Feng, Kee Wui Huang, Bernardo Luis Sabatini
The striatum, the entry nucleus of the basal ganglia, lacks laminar or columnar organization of its principal cells; nevertheless, functional data suggest that it is spatially organized. Here we examine whether the connectivity and synaptic organization of striatal GABAergic interneurons contributes to such spatial organization. Focusing on the two main classes of striatal GABAergic interneurons (fast-spiking interneurons [FSIs] and low-threshold-spiking interneurons [LTSIs]), we apply a combination of optogenetics and viral tracing approaches to dissect striatal microcircuits in mice...
October 5, 2016: Neuron
Pedro A Pereira, Tiago Millner, Manuel Vilela, Sérgio Sousa, Armando Cardoso, M Dulce Madeira
The medial prefrontal cortex (mPFC) has been identified as a critical center for working and long-term memory. In this study, we have examined the expression of neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) in mPFC interneurons and the density of the mPFC cholinergic and dopaminergic innervation in cognitively-impaired aged Wistar rats. We also tested the possibility that the potential age-related changes might rely on insufficient neurotrophic support. The total number of NPY- and VIP-immunoreactive neurons and the density of vesicular acetylcholine transporter (VAChT)- and tyrosine hydroxylase (TH)-immunoreactive varicosities were estimated using stereological methods...
September 21, 2016: Experimental Gerontology
Tanuja Bordia, Danhui Zhang, Xiomara A Perez, Maryka Quik
Tardive dyskinesia (TD) is a drug-induced movement disorder that arises with antipsychotics. These drugs are the mainstay of treatment for schizophrenia and bipolar disorder, and are also prescribed for major depression, autism, attention deficit hyperactivity, obsessive compulsive and post-traumatic stress disorder. There is thus a need for therapies to reduce TD. The present studies and our previous work show that nicotine administration decreases haloperidol-induced vacuous chewing movements (VCMs) in rodent TD models, suggesting a role for the nicotinic cholinergic system...
September 19, 2016: Experimental Neurology
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
Lena C Schmid, Manuel Mittag, Stefanie Poll, Julia Steffen, Jens Wagner, Hans-Rüdiger Geis, Inna Schwarz, Boris Schmidt, Martin K Schwarz, Stefan Remy, Martin Fuhrmann
Alzheimer's disease (AD) is characterized by cognitive decline and neuronal network dysfunction, but the underlying mechanisms remain unknown. In the hippocampus, microcircuit activity during learning and memory processes is tightly controlled by O-LM interneurons. Here, we investigated the effect of beta-amyloidosis on O-LM interneuron structural and functional connectivity, combining two-photon in vivo imaging of synaptic morphology, awake Ca(2+) imaging, and retrograde mono-transsynaptic rabies tracing...
October 5, 2016: Neuron
Danielle A Simmons, Nadia P Belichenko, Ellen C Ford, Sarah Semaan, Marie Monbureau, Sruti Aiyaswamy, Cameron M Holman, Christina Condon, Mehrdad Shamloo, Stephen M Massa, Frank M Longo
Decreases in the ratio of neurotrophic versus neurodegenerative signaling play a critical role in Huntington's disease (HD) pathogenesis and recent evidence suggests that the p75 neurotrophin receptor (NTR) contributes significantly to disease progression. p75(NTR) signaling intermediates substantially overlap with those promoting neuronal survival and synapse integrity and with those affected by the mutant huntingtin (muHtt) protein. MuHtt increases p75(NTR)-associated deleterious signaling and decreases survival signaling suggesting that p75(NTR) could be a valuable therapeutic target...
September 16, 2016: Human Molecular Genetics
Alberto J Rico, Iria G Dopeso-Reyes, Eva Martínez-Pinilla, Diego Sucunza, Diego Pignataro, Elvira Roda, David Marín-Ramos, José L Labandeira-García, Susan R George, Rafael Franco, José L Lanciego
Although it has long been widely accepted that dopamine receptor types D1 and D2 form GPCR heteromers in the striatum, the presence of D1-D2 receptor heteromers has been recently challenged. In an attempt to properly characterize D1-D2 receptor heteromers, here we have used the in situ proximity ligation assay (PLA) in striatal sections comprising the caudate nucleus, the putamen and the core and shell territories of the nucleus accumbens. Experiments were carried out in control macaques as well as in MPTP-treated animals (with and without dyskinesia)...
September 9, 2016: Brain Structure & Function
Thomas W Faust, Maxime Assous, James M Tepper, Tibor Koós
UNLABELLED: Synchronous optogenetic activation of striatal cholinergic interneurons ex vivo produces a disynaptic inhibition of spiny projection neurons composed of biophysically distinct GABAAfast and GABAAslow components. This has been shown to be due, at least in part, to activation of nicotinic receptors on GABAergic NPY-neurogliaform interneurons that monosynaptically inhibit striatal spiny projection neurons. Recently, it has been proposed that a significant proportion of this inhibition is actually mediated by activation of presynaptic nicotinic receptors on nigrostriatal terminals that evoke GABA release from the terminals of the dopaminergic nigrostriatal pathway...
September 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Matthijs B Verhoog, Joshua Obermayer, Christian A Kortleven, René Wilbers, Jordi Wester, Johannes C Baayen, Christiaan P J De Kock, Rhiannon M Meredith, Huibert D Mansvelder
Individual cortical layers have distinct roles in information processing. All layers receive cholinergic inputs from the basal forebrain (BF), which is crucial for cognition. Acetylcholinergic receptors are differentially distributed across cortical layers, and recent evidence suggests that different populations of BF cholinergic neurons may target specific prefrontal cortical (PFC) layers, raising the question of whether cholinergic control of the PFC is layer dependent. Here we address this issue and reveal dendritic mechanisms by which endogenous cholinergic modulation of synaptic plasticity is opposite in superficial and deep layers of both mouse and human neocortex...
2016: Nature Communications
Samira Ztaou, Nicolas Maurice, Jeremy Camon, Gaëlle Guiraudie-Capraz, Lydia Kerkerian-Le Goff, Corinne Beurrier, Martine Liberge, Marianne Amalric
UNLABELLED: Over the last decade, striatal cholinergic interneurons (ChIs) have reemerged as key actors in the pathophysiology of basal-ganglia-related movement disorders. However, the mechanisms involved are still unclear. In this study, we address the role of ChI activity in the expression of parkinsonian-like motor deficits in a unilateral nigrostriatal 6-hydroxydopamine (6-OHDA) lesion model using optogenetic and pharmacological approaches. Dorsal striatal photoinhibition of ChIs in lesioned ChAT(cre/cre) mice expressing halorhodopsin in ChIs reduces akinesia, bradykinesia, and sensorimotor neglect...
August 31, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
C Lecrux, E Hamel
Brain imaging techniques that use vascular signals to map changes in neuronal activity, such as blood oxygenation level-dependent functional magnetic resonance imaging, rely on the spatial and temporal coupling between changes in neurophysiology and haemodynamics, known as 'neurovascular coupling (NVC)'. Accordingly, NVC responses, mapped by changes in brain haemodynamics, have been validated for different stimuli under physiological conditions. In the cerebral cortex, the networks of excitatory pyramidal cells and inhibitory interneurons generating the changes in neural activity and the key mediators that signal to the vascular unit have been identified for some incoming afferent pathways...
October 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Cecilia Tubert, Irene R E Taravini, Eden Flores-Barrera, Gonzalo M Sánchez, María Alejandra Prost, María Elena Avale, Kuei Y Tseng, Lorena Rela, Mario Gustavo Murer
The mechanism underlying a hypercholinergic state in Parkinson's disease (PD) remains uncertain. Here, we show that disruption of the Kv1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing Kv1.3 subunits contribute significantly to the orphan potassium current known as IsAHP in striatal cholinergic interneurons. Typically, this Kv1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons...
September 6, 2016: Cell Reports
Polina Kosillo, Yan-Feng Zhang, Sarah Threlfell, Stephanie J Cragg
Corticostriatal regulation of striatal dopamine (DA) transmission has long been postulated, but ionotropic glutamate receptors have not been localized directly to DA axons. Striatal cholinergic interneurons (ChIs) are emerging as major players in striatal function, and can govern DA transmission by activating nicotinic receptors (nAChRs) on DA axons. Cortical inputs to ChIs have historically been perceived as sparse, but recent evidence indicates that they strongly activate ChIs. We explored whether activation of M1/M2 corticostriatal inputs can consequently gate DA transmission, via ChIs...
August 27, 2016: Cerebral Cortex
Olga Gajewska-Woźniak, Kamil Grycz, Julita Czarkowska-Bauch, Małgorzata Skup
The effects of stimulation of low-threshold proprioceptive afferents in the tibial nerve on two types of excitatory inputs to α-motoneurons were tested. The first input is formed by glutamatergic Ia sensory afferents contacting monosynaptically α-motoneurons. The second one is the cholinergic input originating from V0c-interneurons, located in lamina X of the spinal cord, modulating activity of α-motoneurons via C-terminals. Our aim was to clarify whether enhancement of signaling to ankle extensor α-motoneurons, via direct electrical stimulation addressed predominantly to low-threshold proprioceptive fibers in the tibial nerve of awake rats, will affect Ia glutamatergic and cholinergic innervation of α-motoneurons of lateral gastrocnemius (LG)...
2016: PloS One
Marc Deffains, Liliya Iskhakova, Shiran Katabi, Suzanne N Haber, Zvi Israel, Hagai Bergman
The striatum and the subthalamic nucleus (STN) constitute the input stage of the basal ganglia (BG) network and together innervate BG downstream structures using GABA and glutamate, respectively. Comparison of the neuronal activity in BG input and downstream structures reveals that subthalamic, not striatal, activity fluctuations correlate with modulations in the increase/decrease discharge balance of BG downstream neurons during temporal discounting classical condition task. After induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), abnormal low beta (8-15 Hz) spiking and local field potential (LFP) oscillations resonate across the BG network...
2016: ELife
Keran Ma, JoAnne McLaurin
Alzheimer's disease (AD) is characterized by accumulation and aggregation of beta-amyloid peptide, neurofibrillary tangles of hyperphosphorylated tau, neuroinflammation, synaptic degeneration and eventual neuronal cell loss. Current treatment options for AD provide temporary symptomatic relief in a subset of patients. These drugs include cholinesterase inhibitors that improve cholinergic innervation such as rivastigmine, donepezil and galatamine. In addition, memantine, a N-methyl-D-aspartate antagonist, is used to treat moderate to severe AD by reducing excitotoxicity...
August 19, 2016: Current Alzheimer Research
Andrea Guerra, Alek Pogosyan, Magdalena Nowak, Huiling Tan, Florinda Ferreri, Vincenzo Di Lazzaro, Peter Brown
The human motor cortex has a tendency to resonant activity at about 20 Hz so stimulation should more readily entrain neuronal populations at this frequency. We investigated whether and how different interneuronal circuits contribute to such resonance by using transcranial magnetic stimulation (TMS) during transcranial alternating current stimulation (tACS) at motor (20 Hz) and a nonmotor resonance frequency (7 Hz). We tested different TMS interneuronal protocols and triggered TMS pulses at different tACS phases...
October 2016: Cerebral Cortex
Siddharth Jayakumar, Shlesha Richhariya, O Venkateswara Reddy, Michael J Texada, Gaiti Hasan
Neuronal circuits are known to integrate nutritional information, but the identity of the circuit components is not completely understood. Amino acids are a class of nutrients that are vital for the growth and function of an organism. Here, we report a neuronal circuit that allows Drosophila larvae to overcome amino acid deprivation and pupariate. We find that nutrient stress is sensed by the class IV multidendritic cholinergic neurons. Through live calcium imaging experiments, we show that these cholinergic stimuli are conveyed to glutamatergic neurons in the ventral ganglion through mAChR...
2016: ELife
Benjamin E Reese, Patrick W Keeley
The mature retinal architecture is composed of various types of neuron, each population differing in size and constrained to particular layers, wherein the cells achieve a characteristic patterning in their local organization. These demographic features of retinal nerve cell populations are each complex traits controlled by multiple genes affecting different processes during development, and their genetic determinants can be dissected by correlating variation in these traits with their genomic architecture across recombinant-inbred mouse strains...
August 1, 2016: Progress in Retinal and Eye Research
Masakazu Hamamoto, Emi Kiyokage, Jaerin Sohn, Hiroyuki Hioki, Tamotsu Harada, Kazunori Toida
Odor information is regulated by olfactory inputs, bulbar interneurons, and centrifugal inputs in the olfactory bulb (OB). Cholinergic neurons projecting from the nucleus of the horizontal limb of the diagonal band of Broca and the magnocellular preoptic nucleus are one of the primary centrifugal inputs to the OB. In this study, we focused on cholinergic regulation of the OB and analyzed neural morphology with the particular emphasis on the projection pathways of cholinergic neurons. Single cell imaging of a specific neuron within dense fibers is critical to evaluate the structure and function of the neural circuits...
August 4, 2016: Journal of Comparative Neurology
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