scholarly journals Striatal indirect pathway mediates action switching via modulation of collicular dynamics

2020 ◽  
Author(s):  
Jaeeon Lee ◽  
Bernardo L. Sabatini
Keyword(s):  
Basal Ganglia ◽  
Population Level ◽  
Brain Regions ◽  
Indirect Pathway ◽  
Motor Programs ◽  
Specific Effects ◽  
Motor Actions ◽  
Major Drug ◽  
Selection Of

AbstractType 2 dopamine receptor-expressing, or indirect pathway striatal projection (iSPNs), neurons comprise one of two major pathways through the basal ganglia1, and are a major drug target for treatment of neuropsychiatric disorders2–4. The function of iSPNs is unclear with proposed roles in suppression of unwanted actions and in refining selection actions or their kinematics5–12. Here, we show that iSPNs can simultaneously suppress and facilitate conflicting motor actions in a lateralized licking task. Activation of iSPNs suppresses contraversive while promoting ipsiversive licking, allowing mice to rapidly switch between alternative motor programs. iSPN activity is prokinetic even when mice are not cued to perform an action. Activity in lateral superior colliculus (lSC), a basal ganglia target, is necessary for performing the task and predicts action. Furthermore, iSPN activation suppresses ipsilateral lSC, but surprisingly, excites contralateral lSC. iSPN activity has neuron-specific effects that, at the population level, steers the neural trajectory towards that associated with ipsiversive licking. Thus, our results reveal a previously unknown specificity of iSPNs effects on downstream brain regions, including the ability to excite contralateral regions and trigger motor programs. These results suggest a general circuit mechanism for flexible action switching during competitive selection of lateralized actions.

scholarly journals Neural activity in cortico-basal ganglia circuits of juvenile songbirds encodes performance during goal-directed learning

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jennifer M Achiro ◽  
John Shen ◽  
Sarah W Bottjer
Keyword(s):  
Basal Ganglia ◽  
Population Level ◽  
Response Variability ◽  
Outcome Evaluation ◽  
Acoustic Similarity ◽  
Firing Rates ◽  
Cortical Nucleus ◽  
Directed Learning ◽  
Stages Of Learning ◽  
Motor Actions

Cortico-basal ganglia circuits are thought to mediate goal-directed learning by a process of outcome evaluation to gradually select appropriate motor actions. We investigated spiking activity in core and shell subregions of the cortical nucleus LMAN during development as juvenile zebra finches are actively engaged in evaluating feedback of self-generated behavior in relation to their memorized tutor song (the goal). Spiking patterns of single neurons in both core and shell subregions during singing correlated with acoustic similarity to tutor syllables, suggesting a process of outcome evaluation. Both core and shell neurons encoded tutor similarity via either increases or decreases in firing rate, although only shell neurons showed a significant association at the population level. Tutor similarity predicted firing rates most strongly during early stages of learning, and shell but not core neurons showed decreases in response variability across development, suggesting that the activity of shell neurons reflects the progression of learning.

312-OR: Gender-Specific Effects on Hepatic Fat Metabolism in Type 2 Diabetes before and after Remission

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 312-OR
Author(s):  
AHMAD AL-MRABEH ◽  
SHADEN MELHEM ◽  
SVIATLANA V. ZHYZHNEUSKAYA ◽  
CARL PETERS ◽  
ALISON C. BARNES ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fat Metabolism ◽  
Specific Effects ◽  
Before And After ◽  
Hepatic Fat ◽  
Gender Specific

A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials

2018 ◽  
Vol 15 (5) ◽  
pp. 429-442 ◽  
Author(s):  
Nishant Verma ◽  
S. Natasha Beretvas ◽  
Belen Pascual ◽  
Joseph C. Masdeu ◽  
Mia K. Markey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Latent Variable ◽  
Brain Regions ◽  
Disease Assessment ◽  
Latent Variable Analysis ◽  
The Relationship ◽  
Selection Of

Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.

scholarly journals Cortical neurons exhibit diverse myelination patterns that scale between mouse brain regions and regenerate after demyelination

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cody L. Call ◽  
Dwight E. Bergles
Keyword(s):  
Cortical Neurons ◽  
Regional Differences ◽  
Brain Regions ◽  
Axon Diameter ◽  
Neuronal Identity ◽  
Cortical Areas ◽  
Myelin Sheaths ◽  
Parvalbumin Interneurons ◽  
Selection Of

ABSTRACTAxons in the cerebral cortex show a broad range of myelin coverage. Oligodendrocytes establish this pattern by selecting a cohort of axons for myelination; however, the distribution of myelin on distinct neurons and extent of internode replacement after demyelination remain to be defined. Here we show that myelination patterns of seven distinct neuron subtypes in somatosensory cortex are influenced by both axon diameter and neuronal identity. Preference for myelination of parvalbumin interneurons was preserved between cortical areas with varying myelin density, suggesting that regional differences in myelin abundance arises through local control of oligodendrogenesis. By imaging loss and regeneration of myelin sheaths in vivo we show that myelin distribution on individual axons was altered but overall myelin content on distinct neuron subtypes was restored. Our findings suggest that local changes in myelination are tolerated, allowing regenerated oligodendrocytes to restore myelin content on distinct neurons through opportunistic selection of axons.

scholarly journals The Lamprey Forebrain – Evolutionary Implications

2021 ◽  
pp. 1-16
Author(s):  
Shreyas M. Suryanarayana ◽  
Juan Pérez-Fernández ◽  
Brita Robertson ◽  
Sten Grillner
Keyword(s):  
Basal Ganglia ◽  
Sensory Integration ◽  
Critical Role ◽  
Detailed Comparison ◽  
Common Ancestry ◽  
Dopamine System ◽  
Cortical Areas ◽  
Neural Processes ◽  
Living Group ◽  
Selection Of

The forebrain plays a critical role in a broad range of neural processes encompassing sensory integration and initiation/selection of behaviour. The forebrain functions through an interaction between different cortical areas, the thalamus, the basal ganglia with the dopamine system, and the habenulae. The ambition here is to compare the mammalian forebrain with that of the lamprey representing the oldest now living group of vertebrates, by a review of earlier studies. We show that the lamprey dorsal pallium has a motor, a somatosensory, and a visual area with retinotopic representation. The lamprey pallium was previously thought to be largely olfactory. There is also a detailed similarity between the lamprey and mammals with regard to other forebrain structures like the basal ganglia in which the general organisation, connectivity, transmitters and their receptors, neuropeptides, and expression of ion channels are virtually identical. These initially unexpected results allow for the possibility that many aspects of the basic design of the vertebrate forebrain had evolved before the lamprey diverged from the evolutionary line leading to mammals. Based on a detailed comparison between the mammalian forebrain and that of the lamprey and with due consideration of data from other vertebrate groups, we propose a compelling account of a pan-vertebrate schema for basic forebrain structures, suggesting a common ancestry of over half a billion years of vertebrate evolution.

scholarly journals Expression of FoxP2 in the basal ganglia regulates vocal motor sequences in the adult songbird

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lei Xiao ◽  
Devin P. Merullo ◽  
Therese M. I. Koch ◽  
Mou Cao ◽  
Marissa Co ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Basal Ganglia ◽  
Dopamine Receptor ◽  
Speech Disorders ◽  
Receptor Expression ◽  
Vocal Development ◽  
Motor Actions

AbstractDisruption of the transcription factor FoxP2, which is enriched in the basal ganglia, impairs vocal development in humans and songbirds. The basal ganglia are important for the selection and sequencing of motor actions, but the circuit mechanisms governing accurate sequencing of learned vocalizations are unknown. Here, we show that expression of FoxP2 in the basal ganglia is vital for the fluent initiation and termination of birdsong, as well as the maintenance of song syllable sequencing in adulthood. Knockdown of FoxP2 imbalances dopamine receptor expression across striatal direct-like and indirect-like pathways, suggesting a role of dopaminergic signaling in regulating vocal motor sequencing. Confirming this prediction, we show that phasic dopamine activation, and not inhibition, during singing drives repetition of song syllables, thus also impairing fluent initiation and termination of birdsong. These findings demonstrate discrete circuit origins for the dysfluent repetition of vocal elements in songbirds, with implications for speech disorders.

scholarly journals Targeting Mitochondria in Diabetes

2021 ◽  
Vol 22 (12) ◽  
pp. 6642
Author(s):  
Nina Krako Jakovljevic ◽  
Kasja Pavlovic ◽  
Aleksandra Jotic ◽  
Katarina Lalic ◽  
Milica Stoiljkovic ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Function ◽  
Whole Body ◽  
Noncommunicable Diseases ◽  
Pharmacological Interventions ◽  
Cellular Energy ◽  
Cellular Energy Metabolism ◽  
Data Comparison ◽  
Selection Of

Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.

scholarly journals 18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging evaluation of chorea

2018 ◽  
Vol 10 (3) ◽  
Author(s):  
Nobuyuki Ishii ◽  
Hitoshi Mochizuki ◽  
Miyuki Miyamoto ◽  
Yuka Ebihara ◽  
Kazutaka Shiomi ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Positron Emission Tomography ◽  
Basal Ganglia ◽  
Magnetic Resonance ◽  
Emission Tomography ◽  
Fluorodeoxyglucose Positron Emission Tomography ◽  
Resonance Imaging ◽  
Indirect Pathway ◽  
Positron Emission ◽  
Fluorodeoxyglucose Positron Emission

Chorea is thought to be caused by deactivation of the indirect pathway in the basal ganglia circuit. However, few imaging studies have evaluated the basal ganglia circuit in actual patients with chorea. We investigated the lesions and mechanisms underlying chorea using brain magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). This retrospective case series included three patients with chorea caused by different diseases: hyperglycemic chorea, Huntington’s disease, and subarachnoid hemorrhage. All the patients showed dysfunction in the striatum detected by both MRI and FDG-PET. These neuroimaging findings confirm the theory that chorea is related to an impairment of the indirect pathway of basal ganglia circuit.

The Use of SGLT2i and GLP-1 RA in Patients with Type 2 Diabetes in Thailand: Evidence Review and Recommendations

2021 ◽  
Vol 104 (11) ◽  
pp. 1850-1865
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Lowering ◽  
Sodium Glucose Cotransporter ◽  
Evidence Review ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Lowering Therapy ◽  
The Cost ◽  
Selection Of

Background: Cardiovascular (CV) and renal comorbidities are common among type 2 diabetes (T2D) patients, and significantly increase the cost and burden of care. Both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve key outcomes including major CV events, hospitalization for heart failure, and renal outcomes, albeit to varying degrees in different T2D populations. Materials and Methods: The authors reviewed evidence from GLP-1 RA and SGLT2i CV outcomes trials and real-world studies in Thailand and elsewhere. Results: The authors formulated recommendations to guide selection of anti-diabetes medication based on patients’ clinical characteristics and CV or renal risk profile. Conclusion: These recommendations could help guide management of CV/renal comorbidities and risk alongside glucose-lowering therapy for individual patients. Keywords: Type 2 diabetes mellitus; Cardiovascular diseases; Chronic kidney disease; Clinical outcomes; SGLT2i; GLP-1 RA

Dynamic Changes in the Cortex-Basal Ganglia Network After Dopamine Depletion in the Rat

2008 ◽  
Vol 100 (1) ◽  
pp. 385-396 ◽  
Author(s):  
Cyril Dejean ◽  
Christian E. Gross ◽  
Bernard Bioulac ◽  
Thomas Boraud
Keyword(s):  
Basal Ganglia ◽  
Local Field ◽  
Signal Transmission ◽  
Local Field Potentials ◽  
Cellular Level ◽  
Cortical Activation ◽  
Field Potentials ◽  
Dopamine Depletion ◽  
Indirect Pathway ◽  
Before And After

It is well established that parkinsonian syndrome is associated with alterations in the temporal pattern of neuronal activity and local field potentials in the basal ganglia (BG). An increase in synchronized oscillations has been observed in different BG nuclei in parkinsonian patients and animal models of this disease. However, the mechanisms underlying this phenomenon remain unclear. This study investigates the functional connectivity in the cortex-BG network of a rodent model of Parkinson's disease. Single neurons and local field potentials were simultaneously recorded in the motor cortex, the striatum, and the substantia nigra pars reticulata (SNr) of freely moving rats, and high-voltage spindles (HVSs) were used to compare signal transmission before and after dopaminergic depletion. It is shown that dopaminergic lesion results in a significant enhancement of oscillatory synchronization in the BG: the coherence between pairs of structures increased significantly and the percentage of oscillatory auto- and cross-correlograms. HVS episodes were also more numerous and longer. These changes were associated with a shortening of the latency of SNr response to cortical activation, from 40.5 ± 4.8 to 10.2 ± 1.07 ms. This result suggests that, in normal conditions, SNr neurons are likely to be driven by late inputs from the indirect pathway; however, after the lesion, their shorter latency also indicates an overactivation of the hyperdirect pathway. This study confirms that neuronal signal transmission is altered in the BG after dopamine depletion but also provides qualitative evidence for these changes at the cellular level.

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