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.

Chronic low back pain is common, disabling, and often inadequately controlled with current pharmacologic options, underscoring the need for safer non-opioid treatments. Dronabinol, a synthetic formulation of Δ9-tetrahydrocannabinol, has analgesic potential but has not been rigorously evaluated for chronic low back pain. This article describes a phase IIa, single-site, randomized, double-blind, placebo-controlled, parallel-group trial in Veterans with chronic low back pain. Seventy-five participants will be randomized 2:1 to oral dronabinol or matching placebo for 8 weeks following a screening period of up to 4 weeks. The primary objective is to evaluate safety and tolerability. Primary outcomes include treatment-emergent adverse events, serious adverse events, laboratory findings, vital signs, and electrocardiogram results. Secondary outcomes are exploratory and include pain intensity, physical functioning, emotional functioning, global improvement, analgesic use, and medication adherence. This study is designed to generate safety data and preliminary estimates of variance and effect size to inform a future confirmatory trial; it is not powered to test efficacy hypotheses.Clinical trial registration: http://www.clinicaltrials.gov identifier is NCT06454669.

Nutritional status has been associated with prognosis in several cancers. We investigated whether baseline prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI) as well as their variations during treatment predicted response and survival in extensive-stage small cell lung cancer (ES-SCLC) patients treated with atezolizumab plus chemotherapy. In this multicenter study, records of ES-SCLC patients who received first-line atezolizumab plus platinum-etoposide combination were reviewed retrospectively. Baseline PNI <45 and GNRI <98 were accepted as low. They were reassessed on day 1 of the third cycle to calculate changes from the baseline (ΔPNI and ΔGNRI). Regression models were used to determine predictive factors for response, progression-free and overall survival (PFS and OS). The study included 145 patients. High baseline PNI was independently associated with objective response (odds ratio=2.50, P=0.02). In patients with a low baseline PNI, median PFS was significantly shorter (6.1 vs. 8.7 mo, P=0.04) and it significantly predicted PFS (hazard ratio=1.52, P=0.03). Median OS was significantly shorter in patients with ΔPNI ≤-10% (11.1 vs. 14.9 mo, P=0.01), which independently predicted OS (hazard ratio=2.10, P=0.001). Baseline GNRI and ΔGNRI were not associated with efficacy. However, in patients 65 years of age or older, median PFS was significantly shorter in cases with a low baseline GNRI (7.1 vs. 10.7 mo, P=0.04). PNI and its variations as convenient and cost-effective markers can help predict response and prognosis in ES-SCLC patients receiving first-line atezolizumab plus chemotherapy. GNRI might emerge as an additional prognostic tool in patients 65 years of age or older.

The inability to adopt a hands-on approach can be viewed as a limitation to provide veterinary care virtually. The objective of this study was to establish guidance to support the remote delivery of a companion animal physical examination by video.