The mouse cortico-basal ganglia-thalamic network

Abstract

The 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.

Striatal Direct Pathway Targets Npas1+Pallidal Neurons

“…These results were consistent with the functional anatomy dissected using optogenetic approaches (Figure 1h). In sum, our findings contextualize earlier observations that striatofugal axons are topographically arranged with new cellular insights (Szabo, 1962;Cowan and Powell, 1966;Chang et al, 1981;Wilson and Phelan, 1982;Hedreen and DeLong, 1991;Deniau et al, 1996;Romanelli et al, 2005;Fujiyama et al, 2011;Nambu, 2011;Bertino et al, 2020;Foster et al, 2020;Lee et al, 2020;Okamoto et al, 2020).…”

Reward Processing and Circuit Dysregulation in Posttraumatic Stress Disorder

“…In addition, glutamate afferents convey signals to the NAc about motivational stimuli from prefrontal cortex, basolateral amygdala, and ventral hippocampus (53). Additionally, the NAc receives excitatory afferents from the thalamus and projects back via ventral pallidum (VP) to midline and intralaminar thalamic nuclei that projects to prefrontal cortex, thus completing cortico-striatopallidal-thalamic loops/cortical-basal ganglia circuit (46,54,55).…”

A possible evolutionary function of phenomenal conscious experience of pain

“…In vertebrates, this abstract functional architecture maps rather closely onto the system of multiple parallel circuits that connect the basal ganglia (BG) -an evolutionarily old midbrain structure (Grillner and Robertson, 2016) -via the thalamus, to the forebrain (in mammals, the cortex) and back (Alexander et al, 1986;Redgrave et al, 2013;Friend and Kravitz, 2014). The wiring of this system in the mouse has recently been described in great detail by Foster et al (2020), who also provided for the first time direct evidence for the closed loop-like structure of the parallel circuits. Several key properties of this system that make it relevant to our hypothesis are briefly reviewed below.…”

“…Action selection generally happens under the control of reward signals (Humphries and Prescott, 2010;Redgrave et al, 2011). As discussed by Foster et al (2020), in stimulus-response or habit learning, a stimulus can trigger a hitherto reliably rewarded response, even when reward value is degraded (a runaway process of reward-driven learning can lead not only to habit formation, but also to addiction, both orchestrated by basal ganglia mechanisms; Graybiel, 2008;Redgrave et al, 2010). In contrast, action-outcome learning is goal-directed and results in behavior that is chosen on the basis of the perceived motivational value and estimated obtainability of the outcomecharacteristics that parallel the process of actors bidding on access to control, as posited by our model.…”