Striatal topographical organization: Bridging the gap between molecules, connectivity and behavior

The striatum represents the major hub of the basal ganglia, receiving projections from the entire cerebral cortex and it is assumed to play a key role in a wide array of complex behavioral tasks. Despite being extensively investigated during the last decades, the topographical organization of the striatum is not well understood yet. Ongoing efforts in neuroscience are focused on analyzing striatal anatomy at different spatial scales, to understand how structure relates to function and how derangements of this organization are involved in various neuropsychiatric diseases. While being subdivided at the macroscale level into dorsal and ventral divisions, at a mesoscale level the striatum represents an anatomical continuum sharing the same cellular makeup. At the same time, it is now increasingly ascertained that different striatal compartments show subtle histochemical differences, and their neurons exhibit peculiar patterns of gene expression, supporting functional diversity across the whole basal ganglia circuitry. Such diversity is further supported by afferent connections which are heterogenous both anatomically, as they originate from distributed cortical areas and subcortical structures, and biochemically, as they involve a variety of neurotransmitters. Specifically, the cortico-striatal projection system is topographically organized delineating a functional organization which is maintained throughout the basal ganglia, subserving motor, cognitive and affective behavioral functions. While such functional heterogeneity has been firstly conceptualized as a tripartite organization, with sharply defined limbic, associative and sensorimotor territories within the striatum, it has been proposed that such territories are more likely to fade into one another, delineating a gradient-like organization along medio-lateral and ventro-dorsal axes. However, the molecular and cellular underpinnings of such organization are less understood, and their relations to behavior remains an open question, especially in humans. In this review we aimed at summarizing the available knowledge on striatal organization, especially focusing on how it links structure to function and its alterations in neuropsychiatric diseases. We examined studies conducted on different species, covering a wide array of different methodologies: from tract-tracing and immunohistochemistry to neuroimaging and transcriptomic experiments, aimed at bridging the gap between macroscopic and molecular levels.

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The brain in evolution and involution

Biochemistry and Cell Biology ◽

10.1139/o97-094 ◽

1997 ◽

Vol 75 (6) ◽

pp. 651-667 ◽

Cited By ~ 6

Author(s):

André Parent

Keyword(s):

Basal Ganglia ◽

Substantia Nigra ◽

Functional Organization ◽

Current Model ◽

Brain Structures ◽

Subcortical Structures ◽

Severe Motor ◽

Cortical Inputs ◽

Neuronal Systems ◽

The Brain

This paper provides an overview of the phylogenetic evolution and structural organization of the basal ganglia. These large subcortical structures that form the core of the cerebral hemispheres directly participate in the control of psychomotor behavior. Neuroanatomical methods combined with transmitter localization procedures were used to study the chemical organization of the forebrain in each major group of vertebrates. The various components of the basal ganglia appear well developed in amniote vertebrates, but remain rudimentary in anamniote vertebrates. For example, a typical substantia nigra composed of numerous dopaminergic neurons that project to the striatum already exists in the brain of reptiles. Other studies in mammals show that glutamatergic cortical inputs establish distinct functional territories within the basal ganglia, and that neurons in each of these territories act upon other brain neuronal systems principally via a GABAergic disinhibitory output mechanism. The functional status of the various basal ganglia chemospecific systems was examined in animal models of neurodegenerative diseases, as well as in postmortem material from Parkinson's and Huntington's disease patients. The neurodegenerative processes at play in such conditions specifically target the most phylogenetically ancient components of the brain, including the substantia nigra and the striatum, and the marked involution of these brain structures is accompanied by severe motor and cognitive deficits. Studies of neural mechanisms involved in these akinetic and hyperkinetic disorders have led to a complete reevaluation of the current model of the functional organization of the basal ganglia in both health and disease. Key words: brain phylogeny, basal ganglia, neurotransmitters, neurodegenerative disorders.

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The mouse cortico-basal ganglia-thalamic network

10.1101/2020.10.06.326876 ◽

2020 ◽

Author(s):

Nicholas N. Foster ◽

Laura Korobkova ◽

Luis Garcia ◽

Lei Gao ◽

Marlene Becerra ◽

...

Keyword(s):

Basal Ganglia ◽

Functional Organization ◽

Network Motif ◽

Dorsal Striatum ◽

Thalamic Nuclei ◽

Cortical Areas ◽

Neuropsychiatric Diseases ◽

History Of ◽

Input Source ◽

The Brain

ABSTRACTThe cortico-basal ganglia-thalamic loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behavior, and the natural history of many neurological and neuropsychiatric diseases. Classically, the basal ganglia is conceptualized to contain three primary information output channels: motor, limbic, and associative. However, given the roughly 65 cortical areas and two dozen thalamic nuclei that feed into the dorsal striatum, a three-channel view is overly simplistic for explaining the myriad functions of the basal ganglia. Recent works from our lab and others have subdivided the dorsal striatum into numerous functional domains based on convergent and divergent inputs from the cortex and thalamus. To complete this work, we generated a comprehensive data pool of ∼700 injections placed across the striatum, external globus pallidus (GPe), substantia nigra pars reticulata (SNr), thalamic nuclei, and cortex. We identify 14 domains of SNr, 36 in the GPe, and 6 in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify 6 parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information with complex patterns of convergence and divergence through every elemental node of the entire cortico-basal ganglia loop. These experiments reveal multiple important novel features of the cortico-basal ganglia network motif. The prototypical sub-network structure is characterized by a highly interconnected nature, with cortical information processing through one or more striatal nodes, which send a convergent output to the SNr and a more parallelized output to the GPe; the GPe output then converges with the SNr. A domain of the thalamus receives the nigral output, and is interconnected with both the striatal domains and the cortical areas that filter into its nigral input source. This study provides conceptual advancement of our understanding of the structural and functional organization of the classic cortico-basal ganglia network.

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The Role of the Basal Ganglia in Somatosensory-Motor Interactions: Evidence from Neurophysiology and Behavior

10.3389/978-2-88963-475-0 ◽

2020 ◽

Keyword(s):

Basal Ganglia ◽

And Behavior

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Understanding Emotions: Origins and Roles of the Amygdala

Biomolecules ◽

10.3390/biom11060823 ◽

2021 ◽

Vol 11 (6) ◽

pp. 823

Author(s):

Goran Šimić ◽

Mladenka Tkalčić ◽

Vana Vukić ◽

Damir Mulc ◽

Ena Španić ◽

...

Keyword(s):

Sensory Information ◽

Anterior Cingulate ◽

Central Nucleus ◽

Subcortical Structures ◽

Neuronal Populations ◽

Efferent Projections ◽

Short And Long Term ◽

Understanding Emotions ◽

Fight Or Flight Response ◽

And Behavior

Emotions arise from activations of specialized neuronal populations in several parts of the cerebral cortex, notably the anterior cingulate, insula, ventromedial prefrontal, and subcortical structures, such as the amygdala, ventral striatum, putamen, caudate nucleus, and ventral tegmental area. Feelings are conscious, emotional experiences of these activations that contribute to neuronal networks mediating thoughts, language, and behavior, thus enhancing the ability to predict, learn, and reappraise stimuli and situations in the environment based on previous experiences. Contemporary theories of emotion converge around the key role of the amygdala as the central subcortical emotional brain structure that constantly evaluates and integrates a variety of sensory information from the surroundings and assigns them appropriate values of emotional dimensions, such as valence, intensity, and approachability. The amygdala participates in the regulation of autonomic and endocrine functions, decision-making and adaptations of instinctive and motivational behaviors to changes in the environment through implicit associative learning, changes in short- and long-term synaptic plasticity, and activation of the fight-or-flight response via efferent projections from its central nucleus to cortical and subcortical structures.

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Involvement of Subcortical Structures in the Preparation of Self-Paced Movement

Journal of Psychophysiology ◽

10.1027/0269-8803.18.23.130 ◽

2004 ◽

Vol 18 (2/3) ◽

pp. 130-139 ◽

Cited By ~ 6

Author(s):

Guillermo Paradiso ◽

Danny Cunic ◽

Robert Chen

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Onset Time ◽

Movement Planning ◽

Movement Preparation ◽

Subcortical Structures ◽

Postoperative Mri ◽

Deep Brain

Abstract Although it has long been suggested that the basal ganglia and thalamus are involved in movement planning and preparation, there was little direct evidence in humans to support this hypothesis. Deep brain stimulation (DBS) is a well-established treatment for movement disorders such as Parkinson's disease, tremor, and dystonia. In patients undergoing DBS surgery, we recorded simultaneously from scalp contacts and from electrodes surgically implanted in the subthalamic nucleus (STN) of 13 patients with Parkinson's disease and in the “cerebellar” thalamus of 5 patients with tremor. The aim of our studies was to assess the role of the cortico-basal ganglia-thalamocortical loop through the STN and the cerebello-thalamocortical circuit through the “cerebellar” thalamus in movement preparation. The patients were asked to perform self-paced wrist extension movements. All subjects showed a cortical readiness potential (RP) with onset ranging between 1.5 to 2s before the onset of movement. Subcortical RPs were recorded in 11 of 13 with electrodes in the STN and in 4 of 5 patients with electrodes in the thalamus. The onset time of the STN and thalamic RPs were not significantly different from the onset time of the scalp RP. The STN and thalamic RPs were present before both contralateral and ipsilateral hand movements. Postoperative MRI studies showed that contacts with maximum RP amplitude generally were inside the target nucleus. These findings indicate that both the basal ganglia and the cerebellar circuits participate in movement preparation in parallel with the cortex.

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Double dissociation of single-interval and rhythmic temporal prediction in cerebellar degeneration and Parkinson’s disease

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1810596115 ◽

2018 ◽

Vol 115 (48) ◽

pp. 12283-12288 ◽

Cited By ~ 36

Author(s):

Assaf Breska ◽

Richard B. Ivry

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Cerebellar Degeneration ◽

Common Mechanism ◽

Attentional Orienting ◽

Subcortical Structures ◽

Double Dissociation ◽

Temporal Prediction ◽

Single Interval

Predicting the timing of upcoming events is critical for successful interaction in a dynamic world, and is recognized as a key computation for attentional orienting. Temporal predictions can be formed when recent events define a rhythmic structure, as well as in aperiodic streams or even in isolation, when a specified interval is known from previous exposure. However, whether predictions in these two contexts are mediated by a common mechanism, or by distinct, context-dependent mechanisms, is highly controversial. Moreover, although the basal ganglia and cerebellum have been linked to temporal processing, the role of these subcortical structures in temporal orienting of attention is unclear. To address these issues, we tested individuals with cerebellar degeneration or Parkinson’s disease, with the latter serving as a model of basal ganglia dysfunction, on temporal prediction tasks in the subsecond range. The participants performed a visual detection task in which the onset of the target was predictable, based on either a rhythmic stream of stimuli, or a single interval, specified by two events that occurred within an aperiodic stream. Patients with cerebellar degeneration showed no benefit from single-interval cuing but preserved benefit from rhythm cuing, whereas patients with Parkinson’s disease showed no benefit from rhythm cuing but preserved benefit from single-interval cuing. This double dissociation provides causal evidence for functionally nonoverlapping mechanisms of rhythm- and interval-based temporal prediction for attentional orienting, and establishes the separable contributions of the cerebellum and basal ganglia to these functions, suggesting a mechanistic specialization across timing domains.

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Mouse Corticospinal System Comprises Different Functional Neuronal Ensembles Depending On Their Hodology

10.21203/rs.2.10990/v2 ◽

2019 ◽

Author(s):

Rafael Olivares-Moreno ◽

Mónica López-Hidalgo ◽

Alain Altamirano-Espinoza ◽

Adriana González-Gallardo ◽

Anaid Antaramian ◽

...

Keyword(s):

Spinal Cord ◽

Pyramidal Neurons ◽

Functional Organization ◽

Modular Organization ◽

Subcortical Structures ◽

Neuronal Ensembles ◽

Synaptic Interactions ◽

Spinal Cord Segment ◽

Different Populations ◽

Cortex Slices

Abstract Background: Movement performance depends on the synaptic interactions generated by coherent parallel sensorimotor cortical outputs to different downstream targets. The major outputs of the neocortex to subcortical structures are driven by pyramidal tract neurons (PTNs) located in layer 5B. One of the main targets of PTNs is the spinal cord through the corticospinal (CS) system, which is formed by a complex collection of distinct CS circuits. However, little is known about intracortical synaptic interactions that originate CS commands and how different populations of CS neurons are functionally organized. To further understand the functional organization of the CS system, we analyzed the activity of unambiguously identified CS neurons projecting to different zones of the same spinal cord segment using two-photon calcium imaging and retrograde neuronal tracers. Results: Sensorimotor cortex slices obtained from transgenic mice expressing GCaMP6 funder the Thy1 promoter were used to analyze the spontaneous calcium transients in layer 5 pyramidal neurons. Distinct subgroups of CS neurons projecting to dorsal horn and ventral areas of the same segment show more synchronous activity between them than with other subgroups. Conclusions: The results indicate that CS neurons projecting to different spinal cord zones segregated into functional ensembles depending on their hodology, suggesting that a modular organization of CS outputs controls sensorimotor behaviors in a coordinated manner.

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Disrupted basal ganglia—thalamocortical loops in focal to bilateral tonic-clonic seizures

10.1101/618215 ◽

2019 ◽

Author(s):

Xiaosong He ◽

Ganne Chaitanya ◽

Burcu Asma ◽

Lorenzo Caciagli ◽

Danielle S. Bassett ◽

...

Keyword(s):

Basal Ganglia ◽

Temporal Lobe Epilepsy ◽

Globus Pallidus ◽

Temporal Lobe ◽

Functional Organization ◽

Globus Pallidus Internus ◽

Effective Control ◽

Thalamocortical Connections ◽

Clonic Seizures ◽

Current History

AbstractFocal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, as well as unfavorable treatment outcomes. Achieving greater understanding of its underlying circuitry offers better opportunity to control these particularly serious seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and the cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia—thalamus network with resting-state functional magnetic resonance imaging in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for over one year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of “disconnection” simulations, we showed that these changes in interactive profiles of the basal ganglia—thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between the basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.

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