Cortico-basal ganglia-thalamo-cortical loop

The cortico-basal ganglia-thalamo-cortical loop (CBGTC) is a system of neural pathways in the brain that primarily consists of modulatory dopaminergic projections from the substantia nigra pars compacta 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. The loop is of particular relevance to hyper- and hypo-kinetic movement disorders, such as Parkinson's disease and Huntington's disease, as well as to psychiatric disorders of control, such as ADHD,OCD, and Tourette syndrome.

The circuit consists of modulatory SNc and excitatory cortical inputs into the striatum, where two pathways originate. One pathway is inhibitory, sometimes called the NoGo or indirect pathway, which projects into and inhibits the globus pallidus externus, resulting in the disinhibition of the globus pallidus internus, 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 excitatory pathway, sometimes called the Go or direct pathway, inhibits the globus pallidus internus, 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. The CBGCTC loops may also be divided into limbic and motor loops, with the motor loops containing indirect and direct pathways, which is interconnected with the limbic loop that projects into the ventral striatum. The loop has also been divided into limbic, associative, oculomotor, and motor circuits to explain the role of dopamine in the basal ganglia on motivational states. 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

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