scholarly journals Mediodorsal thalamus contributes to the timing of instrumental actions

2020 ◽  
Author(s):  
Nicholas Lusk ◽  
Warren H. Meck ◽  
Henry H. Yin
Keyword(s):  
Prefrontal Cortex ◽  
Basal Ganglia ◽  
Neural Circuit ◽  
Interval Timing ◽  
Projection Neurons ◽  
Production Task ◽  
Direct Role ◽  
Mediodorsal Thalamus ◽  
Temporal Production

AbstractThe perception of time is critical to adaptive behavior. While prefrontal cortex and basal ganglia have been implicated in interval timing in the seconds to minutes range, little is known about the role of the mediodorsal thalamus (MD), which is a key component of the limbic cortico-basal ganglia-thalamocortical loop. In this study we tested the role of the MD in timing, using an operant temporal production task in male mice. In this task, the expected timing of available rewards is indicated by lever pressing. Inactivation of the MD with muscimol produced rightward shifts in peak pressing on probe trials as well as increases in peak spread, thus significantly altering both temporal accuracy and precision. Optogenetic inhibition of glutamatergic projection neurons in the MD also resulted in similar changes in timing. The observed effects were found to be independent of significant changes in movement. Our findings suggest that the MD is a critical component of the neural circuit for interval timing, without playing a direct role in regulating ongoing performance.Significance StatementThe mediodorsal nucleus of the thalamus (MD) is strongly connected with the prefrontal cortex and basal ganglia, areas which have been implicated in interval timing. Previous work has shown that the MD contributes to working memory and learning of action-outcome contingencies, but its role in behavioral timing is poorly understood. Using an operant temporal production task, we showed that inactivation of the MD significantly impaired timing behavior.

Pathology, Phenomenology and the Dopamine Hypothesis of Schizophrenia

1987 ◽  
Vol 151 (3) ◽  
pp. 288-301 ◽  
Author(s):  
P. J. McKenna
Keyword(s):  
Prefrontal Cortex ◽  
Basal Ganglia ◽  
Functional Role ◽  
Ventral Striatum ◽  
Brain Structures ◽  
Schizophrenic Symptom ◽  
Dopamine Hypothesis ◽  
Dopamine Innervation

The dopamine hypothesis of schizophrenia implies that positive schizophrenic symptoms should be understandable by reference to brain structures receiving a dopamine innervation, or in terms of the functional role of dopamine itself. The basal ganglia, ventral striatum, septo-hippocampal system, and prefrontal cortex, sites of mesotelencephalic dopamine innervation, are examined and it is argued that their dysfunction could form the basis of particular schizophrenic symptom classes. The postulated involvement of dopamine in reinforcement processes might further assist such interpretations. This type of analysis can be extended to other categories of schizophrenic psychopathology.

Intact Proactive Motor Inhibition after Unilateral Prefrontal Cortex or Basal Ganglia Lesions

2021 ◽  
pp. 1-18
Author(s):  
Matthias Liebrand ◽  
Anne-Kristin Solbakk ◽  
Ingrid Funderud ◽  
Macià Buades-Rotger ◽  
Robert T. Knight ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Basal Ganglia ◽  
Contingent Negative Variation ◽  
Motor Preparation ◽  
Motor Inhibition ◽  
Critical Importance ◽  
Electrophysiological Activity ◽  
Preparatory Attention ◽  
External Signals

Previous research provided evidence for the critical importance of the prefrontal cortex (pFC) and basal ganglia (BG) for reactive motor inhibition, that is, when actions are cancelled in response to external signals. Less is known about the role of the pFC and BG in proactive motor inhibition, referring to preparation for an upcoming stop signal. In this study, patients with unilateral lesions to the BG or lateral pFC performed in a cued go/no-go task, whereas their EEG was recorded. The paradigm called for cue-based preparation for upcoming, lateralized no-go signals. Based on previous findings, we focused on EEG indices of cognitive control (prefrontal beta), motor preparation (sensorimotor mu/beta, contingent negative variation [CNV]), and preparatory attention (occipital alpha, CNV). On a behavioral level, no differences between patients and controls were found, suggesting an intact ability to proactively prepare for motor inhibition. Patients showed an altered preparatory CNV effect, but no other differences in electrophysiological activity related to proactive and reactive motor inhibition. Our results suggest a context-dependent role of BG and pFC structures in motor inhibition, being critical in reactive, unpredictable contexts, but less so in situations where one can prepare for stopping on a short timescale.

scholarly journals Role of Individual Basal Ganglia Nuclei in Force Amplitude Generation

2007 ◽  
Vol 98 (2) ◽  
pp. 821-834 ◽  
Author(s):  
Matthew B. Spraker ◽  
Hong Yu ◽  
Daniel M. Corcos ◽  
David E. Vaillancourt
Keyword(s):  
Basal Ganglia ◽  
Motor Cortex ◽  
Globus Pallidus ◽  
Neural Circuit ◽  
Activation Volume ◽  
Force Amplitude ◽  
Percent Signal Change ◽  
Signal Change ◽  
Increased Activity

The basal ganglia-thalamo-cortical loop is an important neural circuit that regulates motor control. A key parameter that the nervous system regulates is the level of force to exert against an object during tasks such as grasping. Previous studies indicate that the basal ganglia do not exhibit increased activity with increasing amplitude of force, although these conclusions are based mainly on the putamen. The present study used functional magnetic resonance imaging to investigate which regions in the basal ganglia, thalamus, and motor cortex display increased activity when producing pinch-grip contractions of increasing force amplitude. We found that the internal portion of the globus pallidus (GPi) and subthalamic nucleus (STN) had a positive increase in percent signal change with increasing force, whereas the external portion of the globus pallidus, anterior putamen, posterior putamen, and caudate did not. In the thalamus we found that the ventral thalamic regions increase in percent signal change and activation volume with increasing force amplitude. The contralateral and ipsilateral primary motor/somatosensory (M1/S1) cortices had a positive increase in percent signal change and activation volume with increasing force amplitude, and the contralateral M1/S1 had a greater increase in percent signal change and activation volume than the ipsilateral side. We also found that deactivation did not change across force in the motor cortex and basal ganglia, but that the ipsilateral M1/S1 had greater deactivation than the contralateral M1/S1. Our findings provide direct evidence that GPi and STN regulate the amplitude of force output. These findings emphasize the heterogeneous role of individual nuclei of the basal ganglia in regulating specific parameters of motor output.

Memory systems, frontal cortex, and the hippocampal axis

1999 ◽  
Vol 22 (3) ◽  
pp. 464-465 ◽  
Author(s):  
Amanda Parker
Keyword(s):  
Prefrontal Cortex ◽  
Episodic Memory ◽  
Frontal Cortex ◽  
Experimental Evidence ◽  
Memory Systems ◽  
Mediodorsal Thalamus ◽  
And Storage

Three comments are made. The proposal that recollection and familiarity-based recognition take different thalamic routes does not fit recent experimental evidence, suggesting that mediodorsal thalamus acts in an integrative role with respect to prefrontal cortex. Second, the role of frontal cortex in episodic memory has been understated. Third, the role of the hippocampal axis is likely to be the computation and storage of ideothetic information.

Prefrontal cortical mechanisms underlying delayed alternation in mice

2012 ◽  
Vol 108 (4) ◽  
pp. 1211-1222 ◽  
Author(s):  
Mark A. Rossi ◽  
Volodya Y. Hayrapetyan ◽  
Benjamin Maimon ◽  
Krystal Mak ◽  
H. Shawn Je ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Dorsal Hippocampus ◽  
Critical Role ◽  
Brain Slices ◽  
Projection Neurons ◽  
Patch Clamp Recording ◽  
Delayed Alternation ◽  
Delayed Alternation Task ◽  
Alternation Task

The prefrontal cortex (PFC) has been implicated in the maintenance of task-relevant information during goal-directed behavior. Using a combination of lesions, local inactivation, and optogenetics, we investigated the functional role of the medial prefrontal cortex (mPFC) in mice with a novel operant delayed alternation task. Task difficulty was manipulated by changing the duration of the delay between two sequential actions. In experiment 1, we showed that excitotoxic lesions of the mPFC impaired acquisition of delayed alternation with long delays (16 s), whereas lesions of the dorsal hippocampus and ventral striatum, areas connected with the PFC, did not produce any deficits. Lesions of dorsal hippocampus, however, significantly impaired reversal learning when the rule was changed from alternation to repetition. In experiment 2, we showed that local infusions of muscimol (an agonist of the GABAA receptor) into mPFC impaired performance even when the animal was well trained, suggesting that the mPFC is critical not only for acquisition but also for successful performance. In experiment 3, to examine the mechanisms underlying the role of GABAergic inhibition, we used Cre-inducible Channelrhodopsin-2 to activate parvalbumin (PV)-expressing GABAergic interneurons in the mPFC of PV-Cre transgenic mice as they performed the task. Using whole cell patch-clamp recording, we demonstrated that activation of PV-expressing interneurons in vitro with blue light in brain slices reliably produced spiking and inhibited nearby pyramidal projection neurons. With similar stimulation parameters, in vivo stimulation significantly impaired delayed alternation performance. Together these results demonstrate a critical role for the mPFC in the acquisition and performance of the delayed alternation task.

scholarly journals Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Marc Deffains ◽  
Liliya Iskhakova ◽  
Shiran Katabi ◽  
Suzanne N Haber ◽  
Zvi Israel ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Field Potential ◽  
Temporal Discounting ◽  
Projection Neurons ◽  
Invasive Treatment ◽  
Cholinergic Interneurons ◽  
Striatal Projection Neurons ◽  
Local Field Potential Lfp ◽  
Spiking Activity

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. Nevertheless, LFP beta oscillations entrain spiking activity of STN, striatal cholinergic interneurons and BG downstream structures, but do not entrain spiking activity of striatal projection neurons. Our results highlight the pivotal role of STN divergent projections in BG physiology and pathophysiology and may explain why STN is such an effective site for invasive treatment of advanced Parkinson's disease and other BG-related disorders.

scholarly journals Transcriptional and epigenetic characterization of early striosomes identifies Foxf2 and Olig2 as factors required for development of striatal compartmentation and neuronal phenotypic differentiation

2020 ◽  
Author(s):  
Maria-Daniela Cirnaru ◽  
Sicheng Song ◽  
Kizito-Tshitoko Tshilenge ◽  
Chuhyon Corwin ◽  
Justyna Mleczko ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Disease Modeling ◽  
Gene Families ◽  
Projection Neurons ◽  
Open Chromatin ◽  
Striatal Projection Neurons ◽  
Human Ipscs ◽  
Open Chromatin Region ◽  
Processing Information

AbstractThe basal ganglia, best known for processing information required for multiple aspects of movement, is also part of a network which regulates reward and cognition. The major output nucleus of the basal ganglia is the striatum, and its functions are dependent on neuronal compartmentation, including striosomes and matrix, which are selectively affected in disease. Striatal projection neurons are GABAergic medium spiny neurons (MSNs), all of which share basic molecular signatures but are subtyped by selective expression of receptors, neuropeptides, and other gene families. Neurogenesis of the striosome and matrix occurs in separate waves, but the factors regulating terminal neuronal differentiation following migration are largely unidentified. We performed RNA- and ATAC-seq on sorted murine striosome and matrix cells at postnatal day 3. Focusing on the striosomal compartment, we validated the localization and role of transcription factors and their regulator(s), previously not known to be associated with striatal development, including Irx1, Foxf2, Olig2 and Stat1/2. In addition, we validated the enhancer function of a striosome-specific open chromatin region located 15Kb downstream of the Olig2 gene. These data and data bases provide novel tools to dissect and manipulate the networks regulating MSN compartmentation and differentiation and thus provide new approaches to establishing MSN subtypes from human iPSCs for disease modeling and drug discovery.

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