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Paola Imbriani, Tommaso Schirinzi, Maria Meringolo, Nicola B Mercuri, Antonio Pisani
Significant advances have been made in the understanding of the numerous mechanisms involved in Parkinson's disease (PD) pathogenesis. The identification of PD pathogenic mutations and the use of different animal models have contributed to better elucidate the processes underlying the disease. Here, we report a brief survey of some relevant cellular mechanisms, including autophagic-lysosomal dysfunction, endoplasmic reticulum stress, and mitochondrial impairment, with the main aim to focus on their potential convergent roles in determining early alterations at the synaptic level, mainly consisting in a decrease in dopamine release at nigrostriatal terminals and loss of synaptic plasticity at corticostriatal synapses...
2018: Frontiers in Neurology
Augusta Pisanu, Laura Boi, Giovanna Mulas, Saturnino Spiga, Sandro Fenu, Anna R Carta
Neuroinflammation is a main component of Parkinson's disease (PD) neuropathology, where unremitting reactive microglia and microglia-secreted soluble molecules such as cytokines, contribute to the neurodegenerative process as part of an aberrant immune reaction. Besides, pro-inflammatory cytokines, predominantly TNF-α, play an important neuromodulatory role in the healthy and diseased brain, being involved in neurotransmitter metabolism, synaptic scaling and brain plasticity. Recent preclinical studies have evidenced an exacerbated neuroinflammatory reaction in the striatum of parkinsonian rats that developed dyskinetic responses following L-DOPA administration...
March 14, 2018: Journal of Neural Transmission
Elizabeth G Pitts, Dan C Li, Shannon L Gourley
Specific corticostriatal structures and circuits are important for flexibly shifting between goal-oriented versus habitual behaviors. For example, the orbitofrontal cortex and dorsomedial striatum are critical for goal-directed action, while the dorsolateral striatum supports habits. To determine the role of neurotrophin signaling, we overexpressed a truncated, inactive form of tropomyosin receptor kinase B [also called tyrosine receptor kinase B (TrkB)], the high-affinity receptor for Brain-derived Neurotrophic Factor, in the orbitofrontal cortex, dorsomedial striatum and dorsolateral striatum...
March 14, 2018: Scientific Reports
John J Marshall, Jian Xu, Anis Contractor
Kainate receptors are members of the glutamate receptor family that function both by generating ionotropic currents through an integral ion channel pore, and through coupling to downstream metabotropic signaling pathways. They are highly expressed in the striatum yet their roles in regulating striatal synapses are not known. Using mice of both sexes we demonstrate that GluK2 containing kainate receptors expressed in direct pathway Spiny Projection Neurons (dSPNs) inhibit glutamate release at corticostriatal synapses in the dorsolateral striatum...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Benjamin R Pittman-Polletta, Allison Quach, Ali I Mohammed, Michael Romano, Krishnakanth Kondabolu, Nancy J Kopell, Xue Han, Michelle M McCarthy
Cortico-basal ganglia-thalamic (CBT) β oscillations (15-30 Hz) are ele- vated in Parkinson's disease and correlated with movement disability. To date, no experimental paradigm outside of loss of dopamine has been able to specifically elevate β oscillations in the CBT loop. Here, we show that activation of striatal cholinergic receptors selectively increased β oscillations in mouse striatum and motor cortex. In individuals showing simultaneous β increases in both striatum and M1, β partial directed coherence (PDC) increased from striatum to M1 (but not in the reverse direction)...
March 12, 2018: European Journal of Neuroscience
T G Adams, B Kelmendi, C A Brake, P Gruner, C L Badour, C Pittenger
Individuals with OCD often identify psychosocial stress as a factor that exacerbates their symptoms, and many trace the onset of symptoms to a stressful period of life or a discrete traumatic incident. However, the pathophysiological relationship between stress and OCD remains poorly characterized: it is unclear whether trauma or stress is an independent cause of OCD symptoms, a triggering factor that interacts with a preexisting diathesis, or simply a nonspecific factor that can exacerbate OCD along with other aspects of psychiatric symptomatology...
January 2018: Chronic Stress
Christine Stubbendorff, Manuel Molano-Mazon, Andrew Mj Young, Todor V Gerdjikov
Rodent striatum is involved in sensory-motor transformations and reward-related learning. Lesion studies suggest dorsolateral striatum, dorsomedial striatum, and nucleus accumbens underlie stimulus-response transformations, goal-directed behaviour and reward expectation respectively. In addition, prefrontal inputs likely control these functions. Here we set out to study how reward-driven behaviour is mediated by the coordinated activity of these structures in the intact brain. We implemented a discrimination task requiring rats to either respond or suppress responding on a lever after the presentation of auditory cues in order to obtain rewards...
March 8, 2018: European Journal of Neuroscience
Ritchy Hodebourg, Jennifer E Murray, Maxime Fouyssac, Mickaël Puaud, Barry J Everitt, David Belin
The alarming increase in heroin overdoses in the USA is a reminder of the need for efficacious and novel treatments for opiate addiction. This may reflect the relatively poor understanding of the neural basis of heroin, as compared to cocaine, seeking behavior. While cocaine reinforcement depends on the mesolimbic system, well established cocaine seeking is dependent on dorsolateral striatum (aDLS) dopamine-dependent mechanisms which are disrupted by N-acetylcysteine, through normalisation of corticostriatal glutamate homeostasis...
March 7, 2018: European Journal of Neuroscience
Yuan-Hao Chen, Tung-Tai Kuo, Jen-Hsin Kao, Eagle Yi-Kung Huang, Tsung-Hsun Hsieh, Yu-Ching Chou, Barry J Hoffer
To determine the influences of exercise on motor deficits and dopaminergic transmission in a hemiparkinson animal model, we measured the effects of exercise on the ambulatory system by estimating spatio-temporal parameters during walking, striatal dopamine (DA) release and reuptake and synaptic plasticity in the corticostriatal pathway after unilateral 6-OHDA lesions. 6-OHDA lesioned hemiparkinsonian rats were exercised on a fixed speed treadmill for 30 minutes per day. Controls received the same lesion but no exercise...
March 5, 2018: Scientific Reports
Orwa Dandash, Murat Yücel, Rothanthi Daglas, Christos Pantelis, Patrick McGorry, Michael Berk, Alex Fornito
Mood disturbances seen in first-episode mania (FEM) are linked to disturbed functional connectivity of the striatum. Lithium and quetiapine are effective treatments for mania but their neurobiological effects remain largely unknown. We conducted a single-blinded randomized controlled maintenance trial in 61 FEM patients and 30 healthy controls. Patients were stabilized for a minimum of 2 weeks on lithium plus quetiapine then randomly assigned to either lithium (serum level 0.6 mmol/L) or quetiapine (dosed up to 800 mg/day) treatment for 12 months...
March 6, 2018: Translational Psychiatry
Marta Maltese, Jennifer Stanic, Annalisa Tassone, Giuseppe Sciamanna, Giulia Ponterio, Valentina Vanni, Giuseppina Martella, Paola Imbriani, Paola Bonsi, Nicola Biagio Mercuri, Fabrizio Gardoni, Antonio Pisani
The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, though it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a +/Δgag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a +/Δgag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation...
March 5, 2018: ELife
Shushu He, Fei Li, Tian Gu, Huayu Ma, Xinyi Li, Shujuan Zou, Xiaoqi Huang, Su Lui, Qiyong Gong, Song Chen
Although temporomandibular disorders (TMD) have been associated with abnormal gray matter volumes in cortical areas and in the striatum, the corticostriatal functional connectivity (FC) of patients with TMD has not been studied. Here, we studied 30 patients with TMD and 20 healthy controls that underwent clinical evaluations, including Helkimo indices, pain assessments, and resting-state functional magnetic resonance imaging scans. The FCs of the striatal regions with the other brain areas were examined with a seed-based approach...
March 5, 2018: Human Brain Mapping
Frances F Loeb, Xueping Zhou, Kirsten E S Craddock, Lorie Shora, Diane D Broadnax, Peter Gochman, Liv S Clasen, Francois M Lalonde, Rebecca A Berman, Karen F Berman, Judith L Rapoport, Siyuan Liu
OBJECTIVE: Working memory (WM) deficits are consistently reported in schizophrenia and are related to poor functional outcomes. Functional magnetic resonance imaging studies of adult-onset schizophrenia have reported decreased functional activations and connectivity in the WM network, but no prior functional magnetic resonance imaging study has examined WM in childhood-onset schizophrenia (COS). The aim of this study was to examine the neural correlates of WM in COS. METHOD: Adult patients with COS (n = 32, 21...
March 2018: Journal of the American Academy of Child and Adolescent Psychiatry
Maxime Assous, James M Tepper
The striatum constitutes the main input structure of the basal ganglia and receives two major excitatory glutamatergic inputs, from the cortex and the thalamus. Excitatory cortico- and thalamo-striatal connections innervate the principal neurons of the striatum, the spiny projection neurons (SPNs), which constitute the main cellular input as well as the only output of the striatum. In addition, corticostriatal and thalamostriatal inputs also innervate striatal interneurons. Some of these inputs have been very well studied, e...
February 26, 2018: European Journal of Neuroscience
Kenji Morita, Ayaka Kato
Dopamine has been suggested to be crucially involved in effort-related choices. Key findings are that dopamine depletion (i) changed preference for a high-cost, large-reward option to a low-cost, small-reward option, (ii) but not when the large-reward option was also low-cost or the small-reward option gave no reward, (iii) while increasing the latency in all the cases but only transiently, and (iv) that antagonism of either dopamine D1 or D2 receptors also specifically impaired selection of the high-cost, large-reward option...
January 2018: ENeuro
George V Rebec
AIMS: This review summarizes evidence for dysfunctional connectivity between cortical and striatal neurons in Huntington's disease (HD), a fatal neurodegenerative condition caused by a single gene mutation. The focus is on data derived from recording of electrophysiological signals in behaving transgenic mouse models. DISCUSSIONS: Firing patterns of individual neurons and the frequency oscillations of local field potentials indicate a disruption in corticostriatal processing driven, in large part, by interactions between cells that contain the mutant gene rather than the mutant gene alone...
February 21, 2018: CNS Neuroscience & Therapeutics
Mieke van Holstein, Monja I Froböse, Jacinta O'Shea, Esther Aarts, Roshan Cools
Motivational, cognitive and action goals are processed by distinct, topographically organized, corticostriatal circuits. We aimed to test whether processing in the striatum is under causal control by cortical regions in the human brain by investigating the effects of offline transcranial magnetic stimulation (TMS) over distinct frontal regions associated with motivational, cognitive and action goal processing. Using a three-session counterbalanced within-subject crossover design, continuous theta burst stimulation was applied over the anterior prefrontal cortex (aPFC), dorsolateral prefrontal cortex, or premotor cortex, immediately after which participants (N = 27) performed a paradigm assessing reward anticipation (motivation), task (cognitive) switching, and response (action) switching...
February 19, 2018: Scientific Reports
P R A Heckman, A Blokland, E P P Bollen, J Prickaerts
The corticostriatal and hippocampal circuits contribute to the neurobiological underpinnings of several neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease and schizophrenia. Based on biological function, these circuits can be clustered into motor circuits, associative/cognitive circuits and limbic circuits. Together, dysfunctions in these circuits produce the wide range of symptoms observed in related neuropsychiatric disorders. Intracellular signaling in these circuits is largely mediated through the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway with an additional role for the cyclic guanosine monophosphate (cGMP)/ protein kinase G (PKG) pathway, both of which can be regulated by phosphodiesterase inhibitors (PDE inhibitors)...
February 15, 2018: Neuroscience and Biobehavioral Reviews
Victor G Gómez-Pineda, Francisco M Torres-Cruz, César I Vivar-Cortés, Elizabeth Hernández-Echeagaray
AIMS: Neurotrophin-3 (NT-3) is expressed in the mouse striatum; however, it is not clear the NT-3 role in striatal physiology. The expression levels of mRNAs and immune localization of the NT-3 protein and its receptor TrkC are altered in the striatum following damage induced by an in vivo treatment with 3-nitropropionic acid (3-NP), a mitochondrial toxin used to mimic the histopathological hallmarks of Huntington's disease (HD). The aim of this study was to evaluate the role of NT-3 on corticostriatal synaptic transmission and its plasticity in both the control and damaged striatum...
February 17, 2018: CNS Neuroscience & Therapeutics
Justin O'Hare, Nicole Calakos, Henry H Yin
Habits have been studied for decades, but it was not until recent years that experiments began to elucidate the underlying cellular and circuit mechanisms. The latest experiments have been enabled by advances in cell-type specific monitoring and manipulation of activity in large neuronal populations. Here we will review recent efforts to understand the neural substrates underlying habit formation, focusing on rodent studies on corticostriatal circuits.
April 2018: Current Opinion in Behavioral Sciences
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