Dopamine is essential for striatal function and learning. Striatal dopamine release can be triggered by dopamine cell firing, but also by coordinated cholinergic interneuron activity, which stimulates dopamine release via presynaptic nicotinic acetylcholine receptors on dopamine axons. While acetylcholine-dependent dopamine release is well-documented ex vivo and under artificial optogenetic stimulation in vivo, its role during natural behavior has remained unclear. One possible endogenous driver of acetylcholine-dependent dopamine release is thalamic input, which provides strong excitatory drive to cholinergic interneurons. To examine whether thalamic input provokes acetylcholine-dependent dopamine release during behavior, we performed simultaneous fiber photometry recordings of striatal dopamine (GRAB-rDA3m) and thalamic axon activity (gCaMP8m) in the dorsomedial (DMS) and dorsolateral striatum (DLS) of mice learning the accelerating rotarod, a striatal-dependent task that demands precise and effortful motor control. Recordings were obtained on- and off-task and across days of training to capture the full arc of learning. Dopamine transients in DMS, but not DLS, were frequently coupled to peaks in thalamic axon activity via an acetylcholine-dependent mechanism. The occurrence of these thalamic-evoked DMS dopamine transients depended on learning, task engagement, and the recent history of dopamine activity, but did not contribute to motor error signals. Together, these findings establish thalamic input as a physiological driver of acetylcholine-dependent dopamine release in DMS. Moreover, they reveal that striatal sensitivity to this local release mechanism is dynamically gated by dopaminergic history, providing a compelling framework for understanding how local and soma-triggered dopamine signals are coordinated to support learning.

High-resolution extracellular electrophysiology is the gold standard for recording spikes from distributed neural populations and is especially powerful when combined with optogenetics for manipulation of specific cell types with high temporal resolution. We integrated these approaches into prototype Neuropixels Opto probes, which combine electronic and photonic circuits. These devices pack 960 electrical recording sites and two sets of 14 light emitters onto a 70-μm-wide, 1-cm-long shank, allowing spatially addressable optogenetic stimulation with blue and red light. In mouse cortex, Neuropixels Opto probes delivered high-quality recordings together with spatially addressable optogenetics, differentially activating or silencing neurons at distinct cortical depths. In the mouse striatum and other deep structures, Neuropixels Opto probes delivered efficient optotagging, facilitating the identification of two cell types in parallel. Neuropixels Opto probes represent a promising tool for recording, identifying and manipulating neuronal populations.

Although learning in response to extrinsic reinforcement is theorized to be driven by dopamine signals that encode the difference between expected and experienced rewards, skills that enable verbal or musical expression can be learned without extrinsic reinforcement. Instead, spontaneous execution of these skills is thought to be intrinsically reinforcing. Whether dopamine signals similarly guide learning of these intrinsically reinforced behaviours is unknown. In juvenile zebra finches learning from an adult tutor, dopamine signalling in a song-specialized basal ganglia region is required for successful song copying, a spontaneous, intrinsically reinforced process. Here we show that dopamine dynamics in the song basal ganglia faithfully track the learned quality of juvenile song performance on a rendition-by-rendition basis. Furthermore, dopamine release in the basal ganglia is driven not only by inputs from midbrain dopamine neurons classically associated with reinforcement learning but also by song premotor inputs, which act by means of local cholinergic signalling to elevate dopamine during singing. Although both cholinergic and dopaminergic signalling are necessary for juvenile song learning, only dopamine tracks the learned quality of song performance. Therefore, dopamine dynamics in the basal ganglia encode performance quality during self-directed, long-term learning of natural behaviours.

Basal Ganglia Advances is a collection highlighting research on the structure, function, and disorders of the basal ganglia. It features studies spanning neuroscience, clinical insights, and computational models, serving as a hub for advances in movement, cognition, and behavior.

Recent advances in the field of Voltage Imaging, with a special focus on new constructs and novel implementations.

Work related to place tuning, spatial navigation, orientation and direction. Mainly includes articles on connectivity in the hippocampus, retrosplenial cortex, and related areas.

Effective transition programs are essential for adolescents and young adults with sickle cell disease (SCD), yet their long-term impact remains unexplored. The St. Jude SCD Transition Program provides structured transition interventions, such as disease education, personal health record (PHR) communication training, transition skills-building, academic guidance, and early adult care introduction for patients aged 12 to 25 years. This 13-year retrospective cohort study evaluated program effectiveness on first adult visit attendance, successful transfer to adult care, adult ambulatory and acute care use, and health-related quality of life (HRQOL). Among 638 patients, 74.5% attended their first adult visit and 40.0% successfully transferred to adult care (2 visits within the first year after transfer). Increased participation in nearly all transition interventions was associated with first adult visit attendance, and all interventions were associated with successful transfer. In-person SCD education and early introduction to adult care were independently associated with first adult visit attendance, whereas in-person SCD education and PHR training were independently associated with successful transfer. A predictive model incorporating intervention exposure and demographics yielded an area under the curve of 0.81 for attendance at the first adult visit (95% confidence interval, 0.75-0.88; sensitivity 0.76, specificity 0.70). PHR training was associated with adult ambulatory use up to 3 years after transfer and improved early adulthood HRQOL. No interventions were associated with acute care use. Transition interventions that improve disease literacy, communication, and care transfer processes are linked to better transition outcomes and HRQOL, though sustained adult care engagement remains low. Future research is needed to promote adult care engagement.

The treatment of acute myeloid leukemia (AML) is a major clinical challenge, with patients often having poor prognoses, especially in subtypes with high-risk genetic profiles. PGAM5 plays a critical role in the progression of various malignancies; however, its biological function and underlying molecular mechanisms in AML remain unclear. The study aimed to systematically investigate the role and potential mechanisms of PGAM5 in AML. Bioinformatics analysis revealed that PGAM5 expression was significantly upregulated in AML patients compared with healthy controls, and high PGAM5 expression was closely associated with unfavorable prognosis. Further analysis suggested that PGAM5 may be related to the PI3K/AKT/mTOR signaling pathway. By establishing AML cell models with PGAM5 knockdown, functional experiments demonstrated that suppressing PGAM5 expression significantly arrested cell cycle progression, inhibited proliferation, and induced apoptosis. Mechanistic studies indicated that PGAM5 is closely associated with glycolytic metabolism in AML and enhances glycolytic flux through the transcription factor HIF-1α. Upon PGAM5 knockdown, AML cells exhibited significant reductions in glucose consumption, ATP production, and lactate output. Furthermore, treatment with the PI3K activator 740Y-P in PGAM5-knockdown cells provided additional evidence that PGAM5 plays a critical role in supporting AML cell proliferation and metabolic reprogramming, suggesting that PGAM5 may represent a candidate molecule for further functional investigation in AML. In summary, this study elucidates the key role of PGAM5 in metabolic remodeling in AML, suggesting its potential as a novel therapeutic target for AML treatment.