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Thalamus orchestrates local acetylcholine-dependent dopamine release in the learning striatum.

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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.

Neuropixels Opto: combining high-resolution electrophysiology and optogenetics.

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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.

Dual neuromodulatory dynamics underlie birdsong learning.

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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.
Latest Updated Curations

Basal Ganglia Advances

 
 
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.

Progress in Voltage Imaging

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

Navigation & Localization

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

Paediatric refraction practices: access to cyclopegia, barriers, and disparities among eye care professionals in Kuala Lumpur.

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Accurate paediatric refraction is essential for detecting and managing vision issues, including latent hyperopia, amblyopia, accommodative esotropia, and progressive myopia. Cycloplegic agents are critical for obtaining precise measurements in children, yet their use varies due to professional, regulatory, and systemic barriers. In Malaysia, where refractive services are divided between the public and private sectors, limited data exist on how eye care professionals implement cycloplegic refraction in paediatric practice.

Eccentric Hexapod external fixator assisted closed reduction and intramedullary nail fixation for the treatment of femoral shaft fractures.

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Closed reduction and intramedullary nail (IMN) fixation remains the gold-standard treatment for femoral shaft fractures (FSFs). However, technical challenges persist in achieving and maintaining anatomical alignment during the closed reduction process. This study aimed to evaluate the clinical efficacy of Hexapod external fixator (HEF)-assisted closed reduction and IMN fixation in the management of FSFs.

Optimizing diabetes self-care in patients with limited health literacy: a randomized controlled trial (RCT) of SCT-based education with and without an AI-designed photo-novel.

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Type 2 diabetes mellitus (T2DM) requires continuous self-care to prevent complications. Patients with limited health literacy often struggle to understand health information and adhere to treatment, resulting in poorer outcomes. Educational interventions tailored to improve self-care and health literacy arSCTe therefore essential. This study evaluated the effectiveness of a Social Cognitive Theory-based intervention, with and without health literacy strategies, in enhancing self-care among patients with T2DM and limited health literacy.
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