Voltage imaging has emerged as a powerful tool for recording membrane potential changes in living cells, offering a direct measurement of rapid neuronal events with high temporal precision. Since the brain is a three-dimensional circuit, it is essential to record signals across a volume. However, achieving effective three-dimensional voltage imaging over large neuronal populations remains challenging due to the need for high imaging speed, high signal-to-noise ratio, and extensive volume coverage. In this study, we demonstrate in vivo three-dimensional voltage imaging in larval zebrafish using oblique plane microscopy and QFDBD-QUAS-driven expression of the genetically encoded voltage indicator Ace-mNeon2-Kv2.1, achieving volumetric imaging rates of up to 200 volumes per second (VPS). This approach enables dye-free voltage imaging, simplifying experimental workflows and improving the reproducibility of in vivo voltage imaging experiments for investigating neuronal circuit dynamics in the living zebrafish animal model.

The neurotransmitter acetylcholine (ACh) is essential in both the central and peripheral nervous systems. Recent studies highlight the significance of interactions between ACh and various neuromodulators in regulating complex behaviors. The ability to simultaneously image ACh and other neuromodulators can provide valuable information regarding the mechanisms underlying these behaviors. Here we developed a series of red fluorescent G-protein-coupled receptor activation-based ACh sensors, with a wide detection range and expanded spectral profile. The high-affinity sensor rACh1h reliably detects ACh release in various brain regions, including the nucleus accumbens, amygdala, hippocampus and cortex. Moreover, rACh1h can be coexpressed with green fluorescent sensors to record ACh release together with other neurochemicals in various behavioral contexts using fiber photometry, mesoscopic imaging and two-photon imaging with high spatiotemporal resolution.

Many open questions about neural circuit and systems function could be answered if spikes and synaptic potentials could be accurately measured from many neurons simultaneously in a given network with cell-type specificity, cellular resolution, and at the millisecond time scale. Voltage imaging with genetically encoded voltage indicators (GEVIs) has advanced to the point that this is now possible for small networks or sparsely labeled neurons, and emerging optical methods promise to soon enable imaging from larger, dense cell populations. This review describes recent discoveries made using GEVIs to understand local and propagating cortical activity, network oscillations, and cortical and hippocampal microcircuit dynamics, and outlines several promising future applications in systems neuroscience.

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.

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.

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.

Iron (Fe) and zinc (Zn) deficiencies severely threaten global human health. Thus, rice biofortification to enhance intrinsic Fe and Zn levels in grains represents an effective strategy to alleviate human Fe and Zn deficiencies. Several biofortification strategies have successfully increased Fe and Zn concentrations in the rice endosperm, with multigene approaches demonstrating synergistic micronutrient accumulation. To enhance Fe and Zn accumulation in rice endosperm, we designed a transformation construct (NYFN) in which OsNRAMP7 and OsNAS2 were driven by the 35S promoter, OsYSL2 by the OsSUT1 promoter, and OsFER2 by the endosperm-specific OsGluA2 promoter. Multi-year field trials were conducted at two locations to evaluate Fe and Zn accumulation in transgenic NYFN rice plants derived from Nipponbare (NB) and commercial cultivar Huaidao 5 (HD5) genetic backgrounds. The results showed that transgenic NB lines exhibited 10.93-14.72 μg/g DW Fe and 33.01-48.33 μg/g DW Zn in polished grains, representing 4.9- to 6.3-fold increases in Fe and 2- to 2.7-fold increases in Zn compared to the NB control. Polished grains of HD5 transformants contained 10.24-13.35 μg/g DW Fe and 32.17-50.33 μg/g DW Zn, corresponding to 4- to 7.4-fold elevations in Fe and 2- to 2.3-fold elevations in Zn relative to the HD5 control. X-ray fluorescence spectroscopy (µ-XRF) and Perls' Prussian blue staining analyses confirmed the significantly enhanced Fe and Zn accumulation in transgenic grains. Transgenic NB lines exhibited significant changes in certain agronomic traits, including reduced 1000-grain weight, grain size, and grain filling rate, whereas transgenic HD5 lines showed no significant agronomic differences relative to the wild type. Total grain weight per plant remained unchanged in both the transgenic NB and HD5 lines compared to the wild type. The results demonstrate that the NYFN strategy enables sustainable Fe and Zn biofortification, representing a promising solution to the global challenge of human Fe and Zn deficiency.