Cholinergic interneurons (CINs) are essential elements of striatal circuits and functions. Although acetylcholine signaling via muscarinic receptors (mAChRs) has been well studied, more recent data indicate that postsynaptic nicotinic receptors (nAChRs) located on striatal GABAergic interneurons (GINs) are equally critical. One example is that CIN stimulation induces large disynaptic inhibition of striatal projection neurons (SPNs) mediated by nAChR activation of GINs. Although these circuits are ideally positioned to modulate striatal output, the neurons involved are not definitively identified because of an incomplete mapping of CINs-GINs interconnections. Here, we show that CINs modulate four GINs populations via an intricate mechanism involving co-activation of presynaptic and postsynaptic mAChRs and nAChRs. Using optogenetics, we demonstrate the participation of tyrosine hydroxylase-expressing GINs in the disynaptic inhibition of SPNs via heterotypic electrical coupling with neurogliaform interneurons. Altogether, our results highlight the importance of CINs in regulating GINs microcircuits via complex synaptic/heterosynaptic mechanisms.

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.

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.

Medicare Advantage enrollment is rising among older adults with kidney failure. Compared with Traditional Medicare, the contracted provider networks and utilization management of Medicare Advantage may introduce friction in transplant evaluation and living donor coordination, potentially restricting access for vulnerable beneficiaries. We examined whether Medicare Advantage is associated with access to living donor kidney transplantation and whether associations vary by rurality, age, or county-level social vulnerability.

Routine implementation of chronic kidney disease research into practice and policy is delayed, fragmented and inconsistent. This workshop aimed to identify strategies to strengthen the implementation of research findings into practice and policy from the perspectives of patients, their caregivers and health professionals.

Chitosan-polyethylene glycol (CS-PEG)-modified long-circulating liposomes were developed and loaded with tanshinone I (TaI@CS-PEG-L) to overcome its poor solubility and low bioavailability, as well as enhance the lipid-lowering efficacy of atorvastatin (At) and mitigate its tissues toxicity. After synthesis of CS-PEG copolymer, it was characterized with infrared and proton nuclear magnetic resonance. Thin-film hydration was used to prepare TaI@CS-PEG-L before optimization was performed using Box-Behnken design. Optimal liposomal formulation was obtained when mass ratio of lecithin:cholesterol:TaI mass ratio was 12:1:1 along with 0.2% CS-PEG, which displayed appropriate particle size (117.41 nm), polydispersity index (0.182), zeta potential (+17.31 mV), encapsulation efficiency (93.15%), and drug loading (5.19%). Besides, the liposomal preparation exhibited good long-term storage stability (over 30 days at 4 °C and 25 °C) and satisfactory gastrointestinal stability in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids for 4 h. TaI@CS-PEG-L displayed increased cellular uptake and in vitro release compared with free TaI and unmodified liposomes. Regarding pharmacokinetic studies, TaI@CS-PEG-L increased AUCₜ, t/, and C in rats by 7.26-fold, 2.43-fold, and 3.12-fold, respectively, which indicates significantly enhanced oral bioavailability. TaI@CS-PEG-L monotherapy markedly lowered serum lipid levels in hyperlipidemic mice, thereby improving liver function indices, and alleviating pathological liver injury. TaI@CS-PEG-L demonstrated synergistic lipid-lowering effects and efficiently reversed At-induced hepatic and pancreatic injuries after combination with At, thus outperforming free TaI and TaI@L. Therefore, CS-PEG-modified long-circulating liposomes could efficiently address delivery challenges of TaI, thereby yielding a formulation that could potently lower serum lipid levels and protect liver against injury. The findings of this study offer a promising 'efficacy-enhancing and toxicity-reducing' strategy for potential treatment of hyperlipidemia in the clinics.