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.

Currently, the elimination of postsurgical osteosarcoma (OS) and defect repair are still separately explored, which is unlike real-world clinical scenarios. Inadequate bone marrow stromal cells (BMSCs) compromise their repair and antitumor efficiencies. Here, PFSSTKT (PFS)-functionalized KLD-12 peptide hydrogels (KLD-PFS) have been engineered and integrated with 2D BiOIO nanosheets to obtain the injectable sono-piezoelectric/pyroelectric peptide hydrogels (KLD-PFS@BiOIO) featuring a supramolecular peptide nanofiber (SMPNF) structure. Differing from the dominant BaTiO in sono-piezoelectric dynamic therapy (SPDT) of cancer, BiOIO nanosheets can produce ROS through sono-piezoelectric and pyroelectric catalytic processes under ultrasound irradiation, thus enabling the combination of SPDT with pyroelectric dynamic therapy against residual OS. More significantly, PFS as a bone marrow homing peptide enables KLD-PFS to capture and recruit more BMSCs, and the inherent SMPNF structure, direct ultrasound-induced current stimuli, sono-piezoelectricity/pyroelectricity-induced current stimuli and ROS birth expedite BMSCs differentiation and bone regeneration. These multifaceted actions follow the signaling pathways associated with calcium flux and cancer-neuron communication disruptions and metabolic dysfunction rectification. They have been successfully validated to repress residual OS and favor bone regeneration in a clinical scenarios-matched postsurgical osteosarcoma and bone defect model. This study offers a promising strategy for comprehensive osteosarcoma management.

Medical biofilms are a significant problem in chronic diseases like diabetic ulcers that do not heal, infections of medical devices and CF. The extracellular polymeric matrix is a barrier to antibiotic penetration. In search of an alternative, approaches based on antimicrobial peptides (AMPs) and enzymes have been developed to tackle the multi-drug resistance. This review collates the existing literature on zoonotic and bacterial origin AMPs, along with the matrix-disrupting and quorum-quenching enzymes, highlighting those which have proven to be effective / against clinical isolates from patients. Enzymes (e.g. cellulase, alginate lyase, and dispersin B) can break down matrix components or block critical signaling molecules and can be seen to have strong synergy with antibiotics, whereas AMPs disrupt cell membranes and downregulate genes that encode biofilm-forming proteins. Our analysis reveals however, a key translational bottleneck: there were no clinical trials in human subjects identified despite strong preclinical evidence of activity. This review discusses these encouraging pre-clinical findings and identifies specific physiological and challenges that need to be overcome to take these alternative therapies to clinical practice.

Salivary pepsin has been proposed as a non-invasive biomarker for diagnosing laryngopharyngeal reflux (LPR); however, its diagnostic utility remains uncertain due to inconsistent findings across studies. This meta-analysis evaluated the diagnostic accuracy of a rapid lateral flow test (Peptest) compared to the reference standard of multichannel intraluminal impedance-pH (MII-pH) monitoring.