Corticostriatal synaptic adaptations in Huntington’s disease

Huntington’s disease (HD) is a progressive neurodegenerative disorder that profoundly impairs corticostriatal information processing. While late stage pathology includes cell death, the appearance of motor symptoms parallels more subtle changes in neuronal function and synaptic integration. Because of the difficulty in modeling the disease and the complexity of the corticostriatal network, understanding the mechanisms driving pathology has been slow to develop. In recent years, advances in animal models and network analysis tools have begun to shed light on the circuit-specific deficits. These studies have revealed a progressive impairment of corticostriatal synaptic signaling in sub-populations of striatal neurons, turning classical excitotoxicity models of HD upside down. Disrupted brain derived neurotrophic factor signaling appears to be a key factor in this decline.

• Publication year

  2015

• Venue

  Current Opinion in Neurobiology

• Publication date

  2015-02-18

• Fields of study

  Medicine, Psychology

• Identifiers
  DOI 10.1016/j.conb.2015.01.020PMID 25700146PMCID 4831704
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Mouse Models of Huntington's Disease.

  2015cited by this paper
• Genetic rescue of CB1 receptors on medium spiny neurons prevents loss of excitatory striatal synapses but not motor impairment in HD mice.

  2014cited by this paper
• Alterations in STriatal‐Enriched protein tyrosine Phosphatase expression, activation, and downstream signaling in early and late stages of the YAC128 Huntington's disease mouse model

  2014influential reference
• Differential loss of thalamostriatal and corticostriatal input to striatal projection neuron types prior to overt motor symptoms in the Q140 knock-in mouse model of Huntington's disease

  2014cited by this paper
• Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington's disease model mice

  2014cited by this paper
• Differential Synaptic and Extrasynaptic Glutamate-Receptor Alterations in Striatal Medium-Sized Spiny Neurons of Aged YAC128 Huntington’s Disease Mice

  2014cited by this paper
• Impaired TrkB receptor signaling underlies corticostriatal dysfunction in Huntington's disease.

  2014cited by this paper
• Cell type-specific plasticity of striatal projection neurons in parkinsonism and L-DOPA-induced dyskinesia

  2014cited by this paper
• Essential role of presynaptic NMDA receptors in activity-dependent BDNF secretion and corticostriatal LTP.

  2014cited by this paper
• Extrasynaptic NMDA receptor involvement in central nervous system disorders.

  2014cited by this paper
• Multiple Sources of Striatal Inhibition Are Differentially Affected in Huntington's Disease Mouse Models

  2013influential reference
• Convergent cortical innervation of striatal projection neurons

  2013cited by this paper
• Role of cerebral cortex in the neuropathology of Huntington's disease

  2013cited by this paper
• Imbalance of p75NTR/TrkB protein expression in Huntington's disease: implication for neuroprotective therapies

  2013cited by this paper
• Dopamine imbalance in Huntington's disease: a mechanism for the lack of behavioral flexibility

  2013cited by this paper
• Loss of corticostriatal and thalamostriatal synaptic terminals precedes striatal projection neuron pathology in heterozygous Q140 Huntington's disease mice.

  2013cited by this paper
• Dysregulation of synaptic proteins, dendritic spine abnormalities and pathological plasticity of synapses as experience-dependent mediators of cognitive and psychiatric symptoms in Huntington's disease.

  2013cited by this paper
• Choosing an animal model for the study of Huntington's disease

  2013cited by this paper
• Direct and GABA‐mediated indirect effects of nicotinic ACh receptor agonists on striatal neurones

  2013cited by this paper
• Suppressing aberrant GluN3A expression rescues synaptic and behavioral impairments in Huntington's disease models

  2013cited by this paper
• Tonic mGluR5/CB1‐dependent suppression of inhibition as a pathophysiological hallmark in the striatum of mice carrying a mutant form of huntingtin

  2013cited by this paper
• Characterization of Neurophysiological and Behavioral Changes, MRI Brain Volumetry and 1H MRS in zQ175 Knock-In Mouse Model of Huntington's Disease

  2012cited by this paper
• triatal atrophy and dendritic alterations in a knockin mouse model of untington ’ s disease enata

  2012cited by this paper
• Color-tuned Channelrhodopsins for Multiwavelength Optogenetics

  2012cited by this paper
• Comprehensive Behavioral and Molecular Characterization of a New Knock-In Mouse Model of Huntington’s Disease: zQ175

  2012cited by this paper
• Cancer incidence in patients with polyglutamine diseases: a population-based study in Sweden.

  2012cited by this paper
• Recurrent network activity drives striatal synaptogenesis

  2012cited by this paper
• Calpain and STriatal-Enriched protein tyrosine phosphatase (STEP) activation contribute to extrasynaptic NMDA receptor localization in a Huntington's disease mouse model.

  2012cited by this paper
• Pathogenic mechanisms in Huntington's disease.

  2011cited by this paper
• Map Formation in the Olfactory Bulb by Axon Guidance of Olfactory Neurons

  2011cited by this paper
• Huntington's disease - neuropathology.

  2011cited by this paper
• Synaptically driven state transitions in distal dendrites of striatal spiny neurons

  2011cited by this paper
• Differential Electrophysiological Changes in Striatal Output Neurons in Huntington's Disease

  2011cited by this paper
• Pathophysiology of Huntington's disease: time-dependent alterations in synaptic and receptor function.

  2011cited by this paper
• Modulation of striatal projection systems by dopamine.

  2011cited by this paper
• Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders

  2010cited by this paper
• Presynaptic BDNF Promotes Postsynaptic Long-Term Potentiation in the Dorsal Striatum

  2010cited by this paper
• Alterations in striatal synaptic transmission are consistent across genetic mouse models of Huntington's disease

  2010cited by this paper
• Developmental regulation and neuroprotective effects of striatal tonic GABAA currents.

  2010cited by this paper
• Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice.

  2010cited by this paper
• Neurotransmitter roles in synaptic modulation, plasticity and learning in the dorsal striatum.

  2010cited by this paper
• Molecular mechanisms and potential therapeutical targets in Huntington's disease.

  2010influential reference
• Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry

  2010cited by this paper
• Genetic mouse models of Huntington’s disease: focus on electrophysiological mechanisms

  2010cited by this paper
• Widespread Decrease of Type 1 Cannabinoid Receptor Availability in Huntington Disease In Vivo

  2010cited by this paper
• Brain-derived neurotrophic factor in neurodegenerative diseases

  2009cited by this paper
• Dopamine D2 Receptor Stimulation Potentiates PolyQ-Huntingtin-Induced Mouse Striatal Neuron Dysfunctions via Rho/ROCK-II Activation

  2009cited by this paper
• Dopamine and synaptic plasticity in dorsal striatal circuits controlling action selection.

  2009cited by this paper
• Endocannabinoid‐dependent plasticity at GABAergic and glutamatergic synapses in the striatum is regulated by synaptic activity

  2009cited by this paper
• New Insights in the Biology of BDNF Synthesis and Release: Implications in CNS Function

  2009cited by this paper
• Differential Excitability and Modulation of Striatal Medium Spiny Neuron Dendrites

  2008cited by this paper
• Differential Tonic GABA Conductances in Striatal Medium Spiny Neurons

  2008cited by this paper
• Full-Length Human Mutant Huntingtin with a Stable Polyglutamine Repeat Can Elicit Progressive and Selective Neuropathogenesis in BACHD Mice

  2008cited by this paper
• Rodent genetic models of Huntington disease.

  2008cited by this paper
• Up-regulation of GLT1 expression increases glutamate uptake and attenuates the Huntington's disease phenotype in the R6/2 mouse.

  2008cited by this paper
• Striatal plasticity and basal ganglia circuit function.

  2008cited by this paper
• The corticostriatal pathway in Huntington's disease.

  2007cited by this paper
• Brain-Derived Neurotrophic Factor Restores Synaptic Plasticity in a Knock-In Mouse Model of Huntington's Disease

  2007cited by this paper
• Role of brain-derived neurotrophic factor in Huntington's disease.

  2007cited by this paper
• Striatal potassium channel dysfunction in Huntington's disease transgenic mice.

  2005cited by this paper
• Pathological cell-cell interactions elicited by a neuropathogenic form of mutant Huntingtin contribute to cortical pathogenesis in HD mice.

  2005cited by this paper
• Increased GABAergic function in mouse models of Huntington's disease: Reversal by BDNF

  2004cited by this paper
• Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules.

  2004cited by this paper
• GABAergic microcircuits in the neostriatum.

  2004cited by this paper
• Genetic mouse models of Huntington's and Parkinson's diseases: illuminating but imperfect.

  2004cited by this paper
• Transient and Progressive Electrophysiological Alterations in the Corticostriatal Pathway in a Mouse Model of Huntington's Disease

  2003cited by this paper
• Time course of early motor and neuropathological anomalies in a knock‐in mouse model of Huntington's disease with 140 CAG repeats

  2003cited by this paper
• Tyrosine kinase B and C receptors in the neostriatum and nucleus accumbens are co-localized in enkephalin-positive and enkephalin-negative neuronal profiles and their expression is influenced by cocaine.

  2003cited by this paper
• Excitatory actions of GABA in the cortex.

  2003cited by this paper
• Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease.

  2003cited by this paper
• GABA generates excitement.

  2003cited by this paper
• Mouse models of Huntington's disease.

  2002cited by this paper
• Loss of Huntingtin-Mediated BDNF Gene Transcription in Huntington's Disease

  2001cited by this paper
• Electrophysiological and morphological changes in striatal spiny neurons in R6/2 Huntington's disease transgenic mice.

  2001cited by this paper
• The pattern of neurodegeneration in Huntington's disease: a comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntington's disease.

  2000cited by this paper
• Clearance of glutamate inside the synapse and beyond.

  1999cited by this paper
• A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration.

  1999cited by this paper
• Pathophysiology of chorea and bradykinesia in Huntington's disease

  1999cited by this paper
• Anterograde transport of brain-derived neurotrophic factor and its role in the brain

  1997cited by this paper
• Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice.

  1996cited by this paper
• A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.

  1993cited by this paper
• Differential loss of striatal projection neurons in Huntington disease.

  1988cited by this paper
• Neurons containing NADPH-diaphorase are selectively resistant to quinolinate toxicity.

  1986cited by this paper
• Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid

  1986cited by this paper
• Neuropathological Classification of Huntington's Disease

  1985cited by this paper

• Effect of electro-acupuncture on motor dysfunction in middle cerebral artery occlusion/reperfusion rats though cortex-striatum somatostatin neural circuit.

  2025cites this paper
• Huntington’s chorea: emerging fields in therapeutics (Review)

  2025cites this paper
• The Role of MicroRNAs in Neurodegeneration: Insights from Huntington’s Disease

  2025cites this paper
• Advancements in surgical treatments for Huntington disease: From pallidotomy to experimental therapies

  2024cites this paper
• Huntington’s disease cellular phenotypes are rescued non-cell autonomously by healthy cells in mosaic telencephalic organoids

  2024cites this paper
• Cortico-basal ganglia plasticity in motor learning.

  2024cites this paper
• Reduced inhibitory synaptic transmission onto striatopallidal neurons may underlie aging-related motor skill deficits.

  2024cites this paper
• Ödül Değerinde Kimyasal Dopamin ve İşlevleri

  2024cites this paper
• A Journey through Huntington's Disease: Exploring Genetics, Neurobiology, and Therapeutic Advances

  2024cites this paper
• Selective vulnerability of layer 5a corticostriatal neurons in Huntington's disease.

  2024cites this paper
• A Practical Guide for Clinical Approach to Patients With Huntington’s Disease in Korea

  2024cites this paper
• Research Progress on Treatment Methods for Huntington’s Disease in China

  2024cites this paper
• UBL3 Interacts with PolyQ-Expanded Huntingtin Fragments and Modifies Their Intracellular Sorting

  2024cites this paper
• Novel EAAT2 activators improve motor and cognitive impairment in a transgenic model of Huntington’s disease

  2023cites this paper
• Neuronal and astrocytic contributions to Huntington's disease dissected with zinc finger protein transcriptional repressors.

  2023cites this paper
• Effective Regulation of Auditory Processing by Parvalbumin Interneurons in the Tail of the Striatum

  2023cites this paper
• Age- and region-dependent cortical excitability in the zQ175 Huntington disease mouse model.

  2023cites this paper
• Dopaminergic Input Regulates the Sensitivity of Indirect Pathway Striatal Spiny Neurons to Brain-Derived Neurotrophic Factor

  2023cites this paper
• Regulatory mechanism of circular RNAs in neurodegenerative diseases

  2023cites this paper
• Break-up and Recovery of Harmony between Direct and Indirect Pathways in The Basal Ganglia; Huntington’s Disease and Treatment

  2023cites this paper
• Microglia and complement mediate early corticostriatal synapse loss and cognitive dysfunction in Huntington’s disease

  2023cites this paper
• Activin A targets extrasynaptic NMDA receptors to improve neuronal and behavioral deficits in a mouse model of Huntington disease

  2023cites this paper
• Serum lipidomics reveal the mechanism of memory disorder improvement by Qifu decoction.

  2023cites this paper
• From Pathogenesis to Therapeutics: A Review of 150 Years of Huntington’s Disease Research

  2023cites this paper
• Cholinergic deficits selectively boost cortical intratelencephalic control of striatum in male Huntington’s disease model mice

  2023cites this paper
• Huntington's Disease: A Clinical Review

  2022cites this paper
• Pridopidine rescues trafficking dynamics and synapse homeostasis in a Huntington disease brain-on-a-chip model

  2022cites this paper
• Corticostriatal Projections Relying on GABA Levels Mediate Exercise-Induced Functional Recovery in Cerebral Ischemic Mice

  2022cites this paper
• Systematic Review and Meta-Analyses of Word Production Abilities in Dysfunction of the Basal Ganglia: Stroke, Small Vessel Disease, Parkinson’s Disease, and Huntington’s Disease

  2022cites this paper
• Focusing the pivotal role of nanotechnology in Huntington’s disease: an insight into the recent advancements

  2022cites this paper
• Pridopidine rescues BDNF/TrkB trafficking dynamics and synapse homeostasis in a Huntington disease brain-on-a-chip model.

  2022cites this paper
• Cannabinoid signaling and risk in Huntington's disease

  2022cites this paper
• Hunting for the cause: Evidence for prion-like mechanisms in Huntington’s disease

  2022cites this paper
• Differential Cellular Balance of Olfactory and Vomeronasal Epithelia in a Transgenic BACHD Rat Model of Huntington’s Disease

  2022cites this paper
• Uncoupling the Excitatory Amino Acid Transporter 2 From Its C-Terminal Interactome Restores Synaptic Glutamate Clearance at Corticostriatal Synapses and Alleviates Mutant Huntingtin-Induced Hypokinesia

  2022cites this paper
• Dysregulation of the Basal Ganglia Indirect Pathway in Early Symptomatic Q175 Huntington's Disease Mice

  2022cites this paper
• Role of mitophagy in mitochondrial quality control: Mechanisms and potential implications for neurodegenerative diseases.

  2021cites this paper
• Dysregulation of the basal ganglia indirect pathway prior to cell loss in the Q175 mouse model of Huntington’s disease

  2021cites this paper
• Microglia Mediate Early Corticostriatal Synapse Loss and Cognitive Dysfunction in Huntington’s Disease Through Complement-Dependent Mechanisms

  2021cites this paper
• Synaptic pathology in Huntington’s disease: Beyond the corticostriatal pathway

  2021cites this paper
• Nicotinamide Adenine Dinucleotide Phosphate Oxidases Are Everywhere in Brain Disease, but Not in Huntington’s Disease?

  2021cites this paper
• Zebrafish an experimental model of Huntington’s disease: molecular aspects, therapeutic targets and current challenges

  2021influential citation
• Mitochondrial Abnormalities and Synaptic Damage in Huntington’s Disease: a Focus on Defective Mitophagy and Mitochondria-Targeted Therapeutics

  2021cites this paper
• CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors

  2021cites this paper
• Altered cortical processing of sensory input in Huntington disease mouse models

  2021cites this paper
• Huntington’s Chorea—a Rare Neurodegenerative Autosomal Dominant Disease: Insight into Molecular Genetics, Prognosis and Diagnosis

  2021cites this paper
• Expression of a modified astrocytic glutamate transporter alleviates Huntington’s hypokinesia, promotes synaptic glutamate clearance and counteracts potentially adverse EAAT2 interactions

  2021cites this paper
• Do Changes in Synaptic Autophagy Underlie the Cognitive Impairments in Huntington’s Disease?

  2021cites this paper
• Impaired Refinement of Kinematic Variability in Huntington Disease Mice on an Automated Home Cage Forelimb Motor Task

  2021cites this paper
• Uniting homeostatic plasticity and exosome biology: A revision of the conceptual framework for drug discovery in neurodegenerative diseases?

  2021cites this paper
• Exposure of R6/2 mice in an enriched environment augments P42 therapy efficacy on Huntington's disease progression.

  2021cites this paper
• Cholinergic de cits selectively boost cortical intratelencephalic control of the striatum in Huntington’s disease

  2021cites this paper
• Enhanced GABAergic Inhibition of Cholinergic Interneurons in the zQ175+/− Mouse Model of Huntington's Disease

  2021cites this paper
• Interleukin-6 deficiency exacerbates Huntington’s disease model phenotypes

  2020cites this paper
• Cortical and Striatal Circuits in Huntington’s Disease

  2020cites this paper
• Phenotypic Variability in Huntington's Disease

  2020cites this paper
• Striatal network modeling in Huntington’s Disease

  2020cites this paper
• Protein changes in synaptosomes of Huntington's disease knock-in mice are dependent on age and brain region.

  2020cites this paper
• ATG14L and ZBTB16: Critical Roles In Aggrephagy In STHdhQ7/Q7 Striatal Neurons

  2020cites this paper
• C-Terminal-Dependent Control of EAAT2 Signaling, Corticostriatal Synaptic Glutamate Clearance and Spontaneous Motor Activity in Mice with Hypokinesia

  2020cites this paper
• Basal Ganglia-A Motion Perspective.

  2020cites this paper
• Purinergic Receptors in Basal Ganglia Diseases: Shared Molecular Mechanisms between Huntington’s and Parkinson’s Disease

  2020cites this paper
• Synaptic Dysfunction in Huntington’s Disease: Lessons from Genetic Animal Models

  2020cites this paper
• Development of biofluid biomarkers for Huntington’s disease

  2020cites this paper
• CYP46A1 gene therapy deciphers the role of brain cholesterol metabolism in Huntington's disease.

  2019cites this paper
• Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington’s disease

  2019cites this paper
• Alterations in synaptic function and plasticity in Huntington disease

  2019cites this paper
• Longitudinal atrophy characterization of cortical and subcortical gray matter in Huntington’s disease patients

  2019cites this paper
• Calcium signalling: A common target in neurological disorders and neurogenesis.

  2019cites this paper
• Mutant huntingtin enhances activation of dendritic Kv4 K+ channels in striatal spiny projection neurons

  2019cites this paper
• Impairment and Restoration of Homeostatic Plasticity in Cultured Cortical Neurons From a Mouse Model of Huntington Disease

  2019cites this paper
• Homeostatic plasticity in neuronal cultures from the YAC128 Huntington disease model mouse

  2019influential citation
• Dysfunctional striatal dopamine signaling in Huntington's disease

  2019cites this paper
• Data-driven computational modelling for some of the implications of dopamine in the brain : From subcellular signalling to area networks

  2018cites this paper
• Molecular insights into cortico-striatal miscommunications in Huntington's disease.

  2018influential citation
• Closing gaps in brain disease-from overlapping genetic architecture to common motifs of synapse dysfunction.

  2018cites this paper
• HttQ111/+ Huntington’s Disease Knock-in Mice Exhibit Brain Region-Specific Morphological Changes and Synaptic Dysfunction

  2018cites this paper
• Thinking Outside the Box (and Arrow): Current Themes in Striatal Dysfunction in Movement Disorders

  2018cites this paper
• Ionotropic and metabotropic glutamate receptors regulate protein translation in co‐cultured nucleus accumbens and prefrontal cortex neurons

  2018cites this paper
• Translating Antisense Technology into a Treatment for Huntington's Disease.

  2018cites this paper
• Antisense oligonucleotides in neurological disorders

  2018cites this paper
• Dichotomous parvalbumin interneuron populations in dorsolateral and dorsomedial striatum

  2018cites this paper
• Huntington's disease: a clinical review

  2018cites this paper
• Choreic movement in striatal infarction: Involvement in cortico-striato-nigral disconnection.

  2018cites this paper
• Monochorea in chronic cerebral hypoperfusion with dopaminergic transmission disruption

  2018cites this paper
• Therapeutic effects of stem cells in rodent models of Huntington's disease: Review and electrophysiological findings

  2018cites this paper
• Astrocytes and presynaptic plasticity in the striatum: Evidence and unanswered questions.

  2018cites this paper
• Pridopidine: Overview of Pharmacology and Rationale for its Use in Huntington’s Disease

  2018cites this paper
• A Clinical Review on Huntington Disease

  2018cites this paper
• Inhibition of TRPC1-Dependent Store-Operated Calcium Entry Improves Synaptic Stability and Motor Performance in a Mouse Model of Huntington’s Disease

  2018cites this paper
• Motor Areas Show Altered Dendritic Structure in an Amyotrophic Lateral Sclerosis Mouse Model

  2017cites this paper
• Neurotrophin biology at NGF 2016: From fundamental science to clinical applications

  2017cites this paper
• Striatal Distribution and Cytoarchitecture of Dopamine Receptor Subtype 1 and 2: Evidence from Double-Labeling Transgenic Mice

  2017cites this paper
• Mitochondrial Metabolism in a Large-Animal Model of Huntington Disease: The Hunt for Biomarkers in the Spermatozoa of Presymptomatic Minipigs

  2017cites this paper
• Huntington’s Disease: Calcium Dyshomeostasis and Pathology Models

  2017cites this paper
• Calcium signaling and molecular mechanisms underlying neurodegenerative diseases.

  2017cites this paper
• Control of Huntington's Disease-Associated Phenotypes by the Striatum-Enriched Transcription Factor Foxp2.

  2017cites this paper
• Brain Regions Showing White Matter Loss in Huntington’s Disease Are Enriched for Synaptic and Metabolic Genes

  2017cites this paper
• Global neuroprotection of huntingtin in culture and alterations of cortico-striatal connections in Huntington’s disease culture and mouse models

  2017cites this paper
• Alterations of Synaptic Function in Huntington's Disease

  2017cites this paper