scholarly journals Chemogenetic inhibition in the dorsal striatum reveals regional specificity of direct and indirect pathway control of action sequencing

2019 ◽  
Author(s):  
Eric Garr ◽  
Andrew R. Delamater
Keyword(s):  
Basal Ganglia ◽  
Instrumental Learning ◽  
Dorsal Striatum ◽  
Training Sequence ◽  
Indirect Pathway ◽  
Action Sequence ◽  
Action Sequences ◽  
Action Sequencing ◽  
Sequence Performance ◽  
Outcome Devaluation

AbstractAnimals engage in intricate action sequences that are constructed during instrumental learning. There is broad consensus that the basal ganglia play a crucial role in the formation and fluid performance of action sequences. To investigate the role of the basal ganglia direct and indirect pathways in action sequencing, we virally expressed Cre-dependent Gi-DREADDs in either the dorsomedial (DMS) or dorsolateral (DLS) striatum during and/or after action sequence learning in D1 and D2 Cre rats. Action sequence performance in D1 Cre rats was slowed down early in training when DREADDs were activated in the DMS, but sped up when activated in the DLS. Acquisition of the reinforced sequence was hindered when DREADDs were activated in the DLS of D2 Cre rats. Outcome devaluation tests conducted after training revealed that the goal-directed control of action sequence rates was immune to chemogenetic inhibition—rats suppressed the rate of sequence performance when rewards were devalued. Sequence initiation latencies were generally sensitive to outcome devaluation, except in the case where DREADD activation was removed in D2 Cre rats that previously experienced DREADD activation in the DMS during training. Sequence completion latencies were generally not sensitive to outcome devaluation, except in the case where D1 Cre rats experienced DREADD activation in the DMS during training and test. Collectively, these results suggest that the indirect pathway originating from the DLS is part of a circuit involved in the effective reinforcement of action sequences, while the direct and indirect pathways originating from the DMS contribute to the goal-directed control of sequence completion and initiation, respectively.

scholarly journals Contributions of the basal ganglia to action sequence learning and performance

2019 ◽  
Author(s):  
Eric Garr
Keyword(s):  
Reinforcement Learning ◽  
Basal Ganglia ◽  
Sequence Learning ◽  
Computational Framework ◽  
Action Sequence ◽  
Action Sequences ◽  
The Hierarchical Structure ◽  
And Performance ◽  
Action Sequencing

Animals engage in intricately woven and choreographed action sequences that are constructed from trial-and-error learning. The mechanisms by which the brain links together individual actions which are later recalled as fluid chains of behavior are not fully understood, but there is broad consensus that the basal ganglia play a crucial role in this process. This paper presents a comprehensive review of the role of the basal ganglia in action sequencing, with a focus on whether the computational framework of reinforcement learning can capture key behavioral features of sequencing and the neural mechanisms that underlie them. While a simple neurocomputational model of reinforcement learning can capture key features of action sequence learning, this model is not sufficient to capture goal-directed control of sequences or their hierarchical representation. The hierarchical structure of action sequences, in particular, poses a challenge for building better models of action sequencing, and it is in this regard that further investigations into basal ganglia information processing may be informative.

scholarly journals The mouse cortico–basal ganglia–thalamic network

Nature ◽  
2021 ◽  
Vol 598 (7879) ◽  
pp. 188-194
Author(s):  
Nicholas N. Foster ◽  
Joshua Barry ◽  
Laura Korobkova ◽  
Luis Garcia ◽  
Lei Gao ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Closed Loop ◽  
Functional Organization ◽  
Dorsal Striatum ◽  
Thalamic Nuclei ◽  
Indirect Pathway ◽  
History Of ◽  
Bona Fide ◽  
External Part ◽  
The Brain

AbstractThe cortico–basal ganglia–thalamo–cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1–4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico–basal ganglia–thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico–basal ganglia–thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.

scholarly journals Dorsal striatum coding for the timely execution of action sequences

2021 ◽  
Author(s):  
Maria Cecilia Martinez ◽  
Camila Lidia Zold ◽  
Mario Gustavo Murer ◽  
Mariano Andrés Belluscio
Keyword(s):  
Neuronal Activity ◽  
Waiting Time ◽  
Dorsal Striatum ◽  
Temporal Discounting ◽  
Time Interval ◽  
Adult Rats ◽  
Action Sequence ◽  
Age Related ◽  
Action Sequences ◽  
Adolescent Rats

The automatic initiation of actions can be highly functional. But occasionally these actions cannot be withheld and are released at inappropriate times, impulsively. Striatal activity has been shown to participate in the timing of action sequence initiation and it has been linked to impulsivity. Using a self-initiated task, we trained adult rats to withhold a rewarded action sequence until a waiting time interval has elapsed. By analyzing neuronal activity we show that the striatal response preceding the initiation of the learned sequence is strongly modulated by the time subjects wait before eliciting the sequence. Interestingly, the modulation is steeper in adolescent rats, which show a strong prevalence of impulsive responses compared to adults. We hypothesize this anticipatory striatal activity reflects the animals' subjective reward expectation, based on the elapsed waiting time, while its steeper waiting modulation in adolescence reflects age-related differences in temporal discounting, internal urgency states or explore-exploit balance.

scholarly journals The role of action effects in motor sequence planning and execution: exploring the influence of temporal and spatial effect anticipation

2021 ◽  
Author(s):  
Rachel M. Brown ◽  
Erik Friedgen ◽  
Iring Koch
Keyword(s):  
Action Planning ◽  
Spatial Effects ◽  
Motor Sequence ◽  
Action Sequence ◽  
Sequential Action ◽  
Spatial Features ◽  
Temporal Features ◽  
Action Sequences ◽  
Temporal And Spatial ◽  
Anticipation Effect

AbstractActions we perform every day generate perceivable outcomes with both spatial and temporal features. According to the ideomotor principle, we plan our actions by anticipating the outcomes, but this principle does not directly address how sequential movements are influenced by different outcomes. We examined how sequential action planning is influenced by the anticipation of temporal and spatial features of action outcomes. We further explored the influence of action sequence switching. Participants performed cued sequences of button presses that generated visual effects which were either spatially compatible or incompatible with the sequences, and the spatial effects appeared after a short or long delay. The sequence cues switched or repeated across trials, and the predictability of action sequence switches was varied across groups. The results showed a delay-anticipation effect for sequential action, whereby a shorter anticipated delay between action sequences and their outcomes speeded initiation and execution of the cued action sequences. Delay anticipation was increased by predictable action switching, but it was not strongly modified by the spatial compatibility of the action outcomes. The results extend previous demonstrations of delay anticipation to the context of sequential action. The temporal delay between actions and their outcomes appears to be retrieved for sequential planning and influences both the initiation and the execution of actions.

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.

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.

#3101 Imbalanced basal ganglia connectivity is associated with motor deficits and apathy in Huntingtons disease: first evidence from human in vivo neuroimaging

2021 ◽  
Vol 92 (8) ◽  
pp. A6.1-A6
Author(s):  
Akshay Nair ◽  
Adeel Razi ◽  
Sarah Gregory ◽  
Robb Rutledge ◽  
Geraint Rees ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Bayesian Model ◽  
Empirical Bayes ◽  
Model Comparison ◽  
De Novo ◽  
Effective Connectivity ◽  
Indirect Pathway ◽  
Direct Pathway ◽  
Bayesian Model Comparison

BackgroundThe gating of movement in humans is thought to depend on activity within the cortico-striato-thalamic loops. Within these loops, emerging from the cells of the striatum, run two opponent pathways the direct and indirect pathway. Both are complex and polysynaptic but the overall effect of activity within these pathways is to encourage and inhibit movement respectively. In Huntingtons disease (HD), the preferential early loss of striatal neurons forming the indirect pathway is thought to lead to disinhibition that gives rise to the characteristic motor features of the condition. But early HD is also specifically associated with apathy, a failure to engage in goal-directed movement. We hypothesised that in HD, motor signs and apathy may be selectively correlated with indirect and direct pathway dysfunction respectively.MethodsUsing a novel technique for estimating dynamic effective connectivity of the basal ganglia, we tested both of these hypotheses in vivo for the first time in a large cohort of patients with prodromal HD (n = 94). We used spectral dynamic casual modelling of resting state fMRI data to model effective connectivity in a model of these cortico-striatal pathways. We used an advanced approach at the group level by combining Parametric Empirical Bayes and Bayesian Model Reduction procedure to generate large number of competing models and compare them by using Bayesian model comparison.ResultsWith this fully Bayesian approach, associations between clinical measures and connectivity parameters emerge de novo from the data. We found very strong evidence (posterior probability > 0.99) to support both of our hypotheses. Firstly, more severe motor signs in HD were associated with altered connectivity in the indirect pathway and by comparison, loss of goal-direct behaviour or apathy, was associated with changes in the direct pathway component of our model.ConclusionsThe empirical evidence we provide here is the first in vivo demonstration that imbalanced basal ganglia connectivity may play an important role in the pathogenesis of some of commonest and disabling features of HD and may have important implications for therapeutics.

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