An open cortico-basal ganglia loop allows limbic control over motor output via the nigrothalamic pathway

Abstract

Cortico-basal ganglia-thalamocortical loops are largely conceived as parallel circuits that process limbic, associative, and sensorimotor information separately. Whether and how these functionally distinct loops interact remains unclear. Combining genetic and viral approaches, we systemically mapped the limbic and motor cortico-basal ganglia-thalamocortical loops in rodents. Despite largely closed loops within each functional domain, we discovered a unidirectional influence of the limbic over the motor loop via ventral striatum-substantia nigra (SNr)-motor thalamus circuitry. Slice electrophysiology verifies that the projection from ventral striatum functionally inhibits nigro-thalamic SNr neurons. In vivo optogenetic stimulation of ventral or dorsolateral striatum to SNr pathway modulates activity in medial prefrontal cortex (mPFC) and motor cortex (M1), respectively. However, whereas the dorsolateral striatum-SNr pathway exerts little impact on mPFC, activation of the ventral striatum-SNr pathway effectively alters M1 activity. These results demonstrate an open cortico-basal ganglia loop whereby limbic information could modulate motor output through ventral striatum control of M1.

Anatomy and Connectivity of the Subthalamic Nucleus in Humans and Non-human Primates

“…More recently, a study on rodents (Aoki et al, 2019) has provided some interesting insight on the anatomo-functional organization of closed and open loop circuits within the rat basal ganglia. By combining genetic and viral approaches, the authors mapped the limbic and motor circuits between the cortex, the basal ganglia and the thalamus in rodents.…”

Interfacing behavioral and neural circuit models for habit formation

“…Other possible circuits that could promote communication between the DMS and DLS include corticostriatothalamic loops (e.g. Aoki et al, ), lateral connections made between striatal subregions (including through interneurons), and basal ganglia loops downstream of the striatum (e.g., through the globus pallidus externa, which sends projections back to the striatum). An ascending spiral circuit might also work in parallel with circuits that dampen rather than promote habit.…”

Heterogeneity in striatal dopamine circuits: Form and function in dynamic reward seeking

“…This continues, back and forth, until the most lateral portion of the SNc, which innervates the DLS and tail portion. This loop architecture has been demonstrated anatomically in both non‐human primates and rodents (Aoki et al, ; Haber et al, ; Ikemoto, ).…”

“…While there is an anatomical basis for striatal loop architecture, and some functional evidence, there is as yet no clear demonstration that serial plasticity across a hypothetical loop starting in ventromedial striatum and ending in dorsolateral striatum occurs during learning. Broadly, it is unclear how VTA, SNc, and ventral and dorsal striatum all interact in vivo , and under what changes in ventral versus dorsal striatal dopamine signaling, as described above, require plasticity outside the striatum, such as engagement of corticostriatal or thalamostriatal inputs (Aoki et al, ; Athalye, Santos, Carmena, & Costa, ; Balleine & O'Doherty, ; Cover et al, ; Gremel & Costa, ; Mandelbaum et al, ; Rothwell et al, ; Smith & Graybiel, ). Notably, relatively little work has examined the central portion of the striatum.…”