Cortico-basal ganglia-thalamo-cortical loop

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Cortico-basal ganglia-thalamo-cortical loop
Basal ganglia circuits.svg
Connections of the basal ganglia.
Details
Part of Cerebrum
Anatomical terms of neuroanatomy

The cortico-basal ganglia-thalamo-cortical loop (CBGTC loop) is a system of neural circuits in the brain. The loop involves connections between the cortex, the basal ganglia, the thalamus, and back to the cortex. It is of particular relevance to hyperkinetic and hypokinetic movement disorders, such as Parkinson's disease and Huntington's disease, [1] as well as to mental disorders of control, such as attention deficit hyperactivity disorder (ADHD), [2] obsessive–compulsive disorder (OCD), [3] and Tourette syndrome. [4]

Contents

The CBGTC loop primarily consists of modulatory dopaminergic projections from the pars compacta of the substantia nigra, and ventral tegmental area as well as excitatory glutamatergic projections from the cortex to the striatum, where these projections form synapses with excitatory and inhibitory pathways that relay back to the cortex. The loop was originally proposed as a part of a model of the basal ganglia called the parallel processing model, which has been criticized and modified into another model called the center surround model. [5]

Current organization schemes characterize cortico-basal ganglia interactions as segregated parallel processing, meaning there is little convergence of distinct cortical areas in the basal ganglia. This is thought to explain the topographically organized functionality of the striatum. [4] The striatum is organized on a rostro-caudal axis, with the rostral putamen and caudate serving associative and cognitive functions and the caudal areas serving sensorimotor function. [6] Sometimes when the striatum is the expressed target the loop is referred to as the cortico-striatal-thalamic-cortical loop. [7]

Neuroanatomy

Indirect and direct pathways. Some neuroanatomy is excluded for simplicity. CBGTC.svg
Indirect and direct pathways. Some neuroanatomy is excluded for simplicity.

The two major input structures of the circuit are the striatum and the subthalamic nucleus (STN). The striatum receives inputs from both the cortex and the pars compacta of the substantia nigra (SNc), while the STN only receives cortical inputs.

Two pathways emerge from the striatum. One pathway is called the indirect (or NoGo) pathway and is inhibitory. This projects to and inhibits the globus pallidus externus (GPe), resulting in the disinhibition of the globus pallidus internus (GPi), leading to inhibition of the thalamus. This pathway also, as a result of inhibiting the GPe, disinhibits the subthalamic nucleus, which results in excitation of the GPi, and therefore inhibition of the thalamus.

The second pathway, is called the direct (or Go) pathway and is excitatory. This pathway inhibits the GPi, resulting in the disinhibition of the thalamus. The direct pathway mostly consists of monosynaptic connections driven by dopamine receptor D1, adenosine A1 receptor, and muscarinic acetylcholine receptor M4, while the indirect pathway relies on connections driven by dopamine receptor D2, adenosine A2A receptor, and muscarinic acetylcholine receptor M1. [1] [8]

The parallel CBGTC loops have been segregated according to the functions of associated cortical regions. One scheme involves the division into limbic and motor loops, with the motor loops containing indirect and direct pathways, which are in turn interconnected with the limbic loop that projects into the ventral striatum. [9] The loop has also been divided into limbic, associative, oculomotor, and motor circuits [4] to explain the role of dopamine in the basal ganglia on motivational states. [10] A five loop division based on primary cortical targets has been described as follows: [11]

A problem identified with the current anatomy of the circuit is that the time delay between the direct and indirect pathways should result in this circuit not working. To overcome this, the center surround hypothesis posits a hyperdirect pathway from the cortex would inhibit other inputs besides one focused cortical input. However, the timing of basal ganglia activity and limb moment, as well as lesion studies do not support this hypothesis. [12]

Function

Two models have been proposed to explain how actions are selected in the basal ganglia. The actor-critic model suggests that actions are generated and evaluated by a "critic" in the ventral striatum, while the actions are carried out by an "actor" in the dorsal striatum. Another model proposes the basal ganglia acts as a selection mechanism, where actions are generated in the cortex and are selected based on context by the basal ganglia. [13] The CBGTC loop is also involved in reward discounting, with firing increasing with an unexpected or greater than expected reward. [2] One review supported the idea that the cortex was involved in learning actions regardless of their outcome, while the basal ganglia was involved in selecting appropriate actions based on associative reward based trial and error learning. [14]

Role in disease

The CBGTC loop has been implicated in many diseases. For example, in Parkinson's disease, degeneration of dopaminergic neurons leading to decreased activity of the excitatory pathway is thought to result in hypokinesia, [15] and in Huntington's disease, degeneration of GABAergic neurons driving the inhibitory pathway is thought to result in the jerky body movements. [2] The co-degeneration of limbic projections along with motor projections may result in many of the psychiatric symptoms of these primarily motor illnesses. [9] In OCD, the loop may be dysfunctional, with an imbalance between the indirect and direct pathways resulting in unwanted thoughts, getting "stuck". [3] In ADHD, decreased tonic dopaminergic signaling resulting in excessive discounting of delayed rewards is thought to result in decreased attention. [2]

Research

The CBGTC loop has been studied in relation to consciousness, action selection, in relation to other circuits, and in the context of memory and cognition. [16] [17] The CBGTC loop model has been criticized as oversimplified and too rigidly applied, given evidence of anatomical and functional overlap and interactions between the direct and indirect pathways. [18] The loop has also been researched in the context of deep brain stimulation. [16] As of 2013 there was intense debate with regards to division of the circuit, pathway interactions, number of pathways and general anatomy. [17]

References

  1. 1 2 Silkis, I. (1 January 2001). "The cortico-basal ganglia-thalamocortical circuit with synaptic plasticity. II. Mechanism of synergistic modulation of thalamic activity via the direct and indirect pathways through the basal ganglia". Bio Systems. 59 (1): 7–14. doi:10.1016/S0303-2647(00)00135-0. ISSN   0303-2647. PMID   11226622.
  2. 1 2 3 4 Maia, Tiago V.; Frank, Michael J. (15 January 2017). "From Reinforcement Learning Models of the Basal Ganglia to the Pathophysiology of Psychiatric and Neurological Disorders". Nature Neuroscience. 14 (2): 154–162. doi:10.1038/nn.2723. ISSN   1097-6256. PMC   4408000 . PMID   21270784.
  3. 1 2 Maia, Tiago V.; Cooney, Rebecca E.; Peterson, Bradley S. (1 January 2008). "The Neural Bases of Obsessive-Compulsive Disorder in Children and Adults". Development and Psychopathology. 20 (4): 1251–1283. doi:10.1017/S0954579408000606. ISSN   0954-5794. PMC   3079445 . PMID   18838041.
  4. 1 2 3 DeLong, Mahlon; Wichmann, Thomas (15 January 2017). "Changing Views of Basal Ganglia Circuits and Circuit Disorders". Clinical EEG and Neuroscience. 41 (2): 61–67. doi:10.1177/155005941004100204. ISSN   1550-0594. PMC   4305332 . PMID   20521487.
  5. ↑ Utter, Amy A.; Basso, Michele A. (1 January 2008). "The basal ganglia: an overview of circuits and function". Neuroscience and Biobehavioral Reviews. 32 (3): 333–342. doi:10.1016/j.neubiorev.2006.11.003. ISSN   0149-7634. PMID   17202023. S2CID   810947.
  6. ↑ Kim, HF; Hikosaka, O (July 2015). "Parallel basal ganglia circuits for voluntary and automatic behaviour to reach rewards". Brain: A Journal of Neurology. 138 (Pt 7): 1776–800. doi:10.1093/brain/awv134. PMC   4492412 . PMID   25981958.
  7. ↑ Fettes, P.; Schulze, L.; Downar, J. (2017). "Cortico-Striatal-Thalamic Loop Circuits of the Orbitofrontal Cortex: Promising Therapeutic Targets in Psychiatric Illness". Frontiers in Systems Neuroscience. 11: 25. doi: 10.3389/fnsys.2017.00025 . PMC   5406748 . PMID   28496402.
  8. ↑ Parent, A.; Hazrati, L. N. (1 January 1995). "Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop". Brain Research. Brain Research Reviews. 20 (1): 91–127. doi:10.1016/0165-0173(94)00007-C. PMID   7711769. S2CID   28252990.
  9. 1 2 NF, Mehrabi; Malvindar, Singh-Bains; Henry, Waldvogel; Richard, Faull (21 July 2016). "Cortico-Basal Ganglia Interactions in Huntington's Disease".{{cite journal}}: Cite journal requires |journal= (help)
  10. ↑ Ikemoto, Satoshi; Yang, Chen; Tan, Aaron (1 September 2015). "Basal ganglia circuit loops, dopamine and motivation: A review and enquiry". Behavioural Brain Research. 290: 17–31. doi:10.1016/j.bbr.2015.04.018. PMC   4447603 . PMID   25907747.
  11. ↑ Squire, Larry (2013). Fundamental neuroscience (4th. ed.). Amsterdam: Elsevier/Academic Press. p. 728. ISBN   978-0-12-385870-2.
  12. ↑ DeLong, Mahlon; Wichmann, Thomas (15 January 2017). "Update on models of basal ganglia function and dysfunction". Parkinsonism & Related Disorders. 15 (Suppl 3): S237 –S240. doi:10.1016/S1353-8020(09)70822-3. ISSN   1353-8020. PMC   4275124 . PMID   20082999.
  13. ↑ Redgrave, P.; Prescott, T.J.; Gurney, K. (April 1999). "The Basal Ganglia: A Vertebrate Solution to the Selection Problem?". Neuroscience. 89 (4): 1009–1023. CiteSeerX   10.1.1.32.4792 . doi:10.1016/S0306-4522(98)00319-4. PMID   10362291. S2CID   3187928.
  14. ↑ Hélie, Sébastien; Ell, Shawn W.; Ashby, F. Gregory (1 March 2015). "Learning robust cortico-cortical associations with the basal ganglia: an integrative review". Cortex. 64: 123–135. doi:10.1016/j.cortex.2014.10.011. ISSN   1973-8102. PMID   25461713. S2CID   17994331.
  15. ↑ Lanciego, José L.; Luquin, Natasha; Obeso, José A. (15 January 2017). "Functional Neuroanatomy of the Basal Ganglia". Cold Spring Harbor Perspectives in Medicine. 2 (12) a009621. doi:10.1101/cshperspect.a009621. ISSN   2157-1422. PMC   3543080 . PMID   23071379.
  16. 1 2 Brittain, JS; Sharott, A; Brown, P (June 2014). "The highs and lows of beta activity in cortico-basal ganglia loops". The European Journal of Neuroscience. 39 (11): 1951–9. doi:10.1111/ejn.12574. PMC   4285950 . PMID   24890470.
  17. 1 2 Schroll, Henning; Hamker, Fred H. (30 December 2013). "Computational models of basal-ganglia pathway functions: focus on functional neuroanatomy". Frontiers in Systems Neuroscience. 7: 122. doi: 10.3389/fnsys.2013.00122 . PMC   3874581 . PMID   24416002.
  18. ↑ Calabresi, Paolo; Picconi, Barbara; Tozzi, Alessandro; Ghiglieri, Veronica; Filippo, Massimiliano Di (1 August 2014). "Direct and indirect pathways of basal ganglia: a critical reappraisal". Nature Neuroscience. 17 (8): 1022–1030. doi:10.1038/nn.3743. PMID   25065439. S2CID   8983260.
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