Editorial: Updates and discussions about basal ganglia and their circuits

The basal ganglia (BG) comprise a complex network of interconnected subcortical nuclei traditionally including the striatum (caudate nucleus, putamen, and nucleus accumbens), globus pallidus (internal and external), subthalamic nucleus, and substantia nigra (pars compacta and pars reticulata) (Lanciego et al., 2012; Calabresi et al., 2014). Although historically associated with motor control, these regions are now recognized as participating in a broad range of functions involving cognition, motivation, reward processing, and emotional regulation (Graybiel, 2000; Obeso et al., 2000).

In this context, this canonical model, together with the extensive dopaminergic, glutamatergic, and GABAergic connectivity of the basal ganglia, still provides an important basis for understanding their functional diversity. In particular, the nigrostriatal, mesolimbic, and mesocortical dopaminergic pathways originating mainly from the substantia nigra pars compacta and ventral tegmental area, remain central to our understanding of neuropathological disorders such as Parkinson's and Huntington's diseases (Björklund and Dunnett, 2007).

As previously discussed, by Gerfen (2023), the classical models of BG organization proposed that the direct and indirect pathways exert opposing influences over movement, with the former facilitating and the latter suppressing motor actions, respectively. In parallel, the hyperdirect pathway, characterized by excitatory cortical projections to the subthalamic nucleus, reinforces inhibitory basal ganglia output and further contributes to movement regulation (Nelson and Kreitzer, 2014).

In fact, this framework remains highly influential from both conceptual and didactic perspectives. However, recent studies have demonstrated concurrent activation of both pathways during movement initiation and execution, challenging the traditional “go/no-go” interpretation of basal ganglia function. Additionally, recent findings indicate that non-canonical striosomal direct and indirect pathways may modulate dopamine release and motor behavior in ways that extend beyond the traditional matrix-based circuitry, adding another layer of complexity to current models of basal ganglia function (Cui et al., 2013; Varin et al., 2023; Rocha et al., 2026).

In this Research Topic, the submitted manuscripts explore multiple dimensions of basal ganglia research, ranging from classical neuroanatomical organization to contemporary imaging and therapeutic perspectives. Together, these studies reinforce the steadfast relevance of basal ganglia investigations for both basic and translational neuroscience.

A solid conceptual foundation was laid by Rocha et al., whose mini-review addresses the functional anatomy, neurochemistry, and circuit dynamics of the basal ganglia, with particular focus on the direct and indirect pathways and their dopaminergic modulation in voluntary movement. This timely review serves as an introduction for the more specialized works that follow.

The dopaminergic system was revisited here from two complementary angles. Guissoni Campos et al. investigated the expression of clock proteins Per1, Per2, and Cry1 in the substantia nigra and subthalamic nucleus of Sapajus apella, a diurnal primate, and concluded that these circadian regulators are present in key motor areas of the basal ganglia. Conversely, Azambuja et al. examined whether normal aging causes detectable loss of TH-immunopositive neurons or volumetric changes in the substantia nigra pars compacta and ventral tegmental area of the common marmoset.

Striatal vulnerability under chronic stress was the focus of Lira-Bandeira et al., who used stereological methods to evaluate the effects of social isolation and ayahuasca treatment on striatal neurons in juvenile marmosets. Furthermore, two contributions examined basal ganglia pathology through neuroimaging. Wang et al. explored the relationship between enlarged perivascular spaces in the basal ganglia and cerebral perfusion in elderly patients, while Zuo et al. used resting-state fMRI to assess cerebellar-cerebral connectivity in patients with cognitive impairment after basal ganglia stroke.

The final two articles addressed therapeutic possibilities. Singh and Reynolds reviewed the application of focused ultrasound to basal ganglia disorders, covering mechanisms ranging from thermal ablation and blood-brain barrier opening to neuromodulation and sonogenetics, with a discussion of early clinical evidence in Parkinson's disease, essential tremor, and dystonia. Lucena et al. took a different approach, systematically reviewing the neuroprotective effects of marine algae-derived polysaccharides in animal models of basal ganglia neurodegeneration.

Collectively, these articles demonstrate progress of basal ganglia research, from cellular morphology and circadian biology to functional neuroimaging and therapeutic innovation. We believe this assemblage of studies will be useful to both researchers approaching this complex topic for the first time and those already contributing to the field.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Footnotes

Edited and reviewed by: Javier DeFelipe, Universidad Politécnica de Madrid, Spain