Thalamus orchestrates local acetylcholine-dependent dopamine release in the learning striatum.
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.
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.
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.
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Most Popular Recent Articles
How Does Targeted Human Milk Fortification Influence Body Composition and Growth in Preterm Infants? A Narrative Literature Review.
Preterm infants fed human milk (HM) require additional calories and nutrients, as unfortified HM alone is inadequate to support optimal growth and body composition. Fortification methods have evolved to include targeted fortification (TF), based on measured macronutrient content of HM, rather than standard fortification (SF), which relies on assumed HM composition. The energy, protein-to-energy ratio, and macronutrient content of HM influence fat mass (FM) and fat-free mass (FFM) accretion, key factors for neurodevelopment and long-term metabolic health. This narrative literature review evaluated the impact of TF versus SF on body composition among preterm infants.
Uncovering the role of ABI2 as a key regulator of flowering time in Arabidopsis.
Abscisic acid (ABA) is a fundamental regulator of plant development, growth, and drought adaptation, and it modulates the transition to flowering. However, the molecular mechanisms by which ABA delays flowering remain unclear. Recently, ABA INSENSITIVE 2 (ABI2), a core component of the ABA signaling pathway, was reported to positively regulate floral transition in . The expression of floral repressors such as and was strongly upregulated, whereas flowering promoting genes including , and were downregulated in the mutant. Moreover, ABI5 protein levels and phosphorylation status were enhanced in , suggesting that ABI2 reduces ABI5 activity and suppresses the activation of its target genes, such as . Genetic analyses revealed that ABI2 functions upstream of ABI5. In conclusion, these findings indicate that ABI2 is a major switch that fine-tunes the crosstalk between ABA signaling and floral transition in .
A multiple-choice SDT model for cognitive diagnosis models.
A model for multiple-choice (MC) items based on signal detection theory (SDT), the MC-SDT model (DeCarlo, 2021a), follows from assumptions about perceptual and decision processes involved when examinees choose alternatives for MC items. The model can be expressed as a hierarchical model with an 'item-level', Level 1, and an 'examinee-level', Level 2. Here it is shown that cognitive diagnosis models (CDMs) can also be viewed as consisting of two levels, with the MC-SDT model serving as the first-level model, whereas the second-level model determines the type of CDM. Thus, the theory about how examinees make choices for MC items is unified across different CDMs. The resulting MC-SDT-CDM models are shown to be parsimonious sub-models of MC-CDMs. The models have straightforward interpretations (MC-SDT at Level 1), avoid estimation problems, and are useful for small sample sizes. The models are illustrated with an application to MC items from the TIMSS 2007 4th grade exam.