This brief review summarizes the most recent progress in in vivo voltage imaging in the neurosciences, as an extension to the work presented at the voltage imaging session of the 2025 FENS regional meeting in Oslo. First, we outline the latest advances in genetically encoded voltage indicators. Next, we examine technical innovations that have reshaped imaging platforms and lay the groundwork to investigate neural activity in real time across large fields of view and in deep tissue. Finally, we highlight a selection of compelling applications that have emerged over the past 5 years, illustrating how voltage imaging evolved from a proof of concept to being deployed to answer pending neuroscientific questions.

Striatum processes a wide range of functions including goal-directed behavior and habit formation, respectively encoded by the dorsomedial striatum (DMS) and dorsolateral striatum (DLS). GABAergic feedforward inhibition is known to control the integration of cortical information by striatal projection neurons (SPNs). Here we questioned whether this control is specific between distinct striatal functional territories. Using opto-activation and opto-inhibition of identified GABAergic interneurons, we found that different circuits are engaged in DLS and DMS, both ex vivo and in vivo: while parvalbumin interneurons efficiently control SPNs in DLS, somatostatin interneurons control SPNs in DMS. Moreover, both parvalbumin and somatostatin interneurons use a dual hyperpolarizing/depolarizing effect to control cortical input integration depending on SPN activity state: GABAergic interneurons potently inhibit spiking SPNs while in resting SPNs, they favor cortical activity summation via a depolarizing effect. Our findings establish that striatal GABAergic interneurons exert efficient territory-specific and state-dependent control of SPN activity and functional output.

Activity of the mesolimbic dopamine system has long been implicated in encoding primary rewards and contributing to the addictive properties of drugs of abuse. Dopamine neurons in the ventral tegmental area (VTA) of the midbrain typically show patterns of spontaneous burst activity that align with the onset of salient events or rewarding stimuli, resulting in phasic dopamine release in the nucleus accumbens (NAc). Fiber photometry is increasingly being used as an accessible technique to quantify neural activity with high temporal resolution at sensors offering signal specificity in stable recordings over extended periods of time. It has been well established by multiple techniques that opioids increase mesolimbic dopamine activity, likely through disinhibition of VTA neurons. Here we used fiber photometry to compare sub-second transient events from VTA neurons with GCaMP6f and dopamine release in the lateral shell of the NAc with dLight1.3b and GRABDA2h in response to morphine treatment. In weekly sessions, one dose of morphine was administered in escalating order (2.5, 5,7.5, and 10 mg/kg, intraperitoneal). Consistent with prior literature, both GCaMP6f in VTA neurons and dLight1.3b in NAc showed patterns of increased signal following morphine treatment. In contrast, morphine suppressed transient activity at GRABDA2h sensors. Further analyses of whole signal streams from each sensor showed a generalized increase, but reduction in variability of the GRABDA2h signal, consistent with the interpretation of sensor saturation. Such results emphasize the importance of the inclusion of appropriate controls to contextualize the interpretation of biosensor responses, particularly in response to pharmacological treatment.

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

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.

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

This brief review summarizes the most recent progress in in vivo voltage imaging in the neurosciences, as an extension to the work presented at the voltage imaging session of the 2025 FENS regional meeting in Oslo. First, we outline the latest advances in genetically encoded voltage indicators. Next, we examine technical innovations that have reshaped imaging platforms and lay the groundwork to investigate neural activity in real time across large fields of view and in deep tissue. Finally, we highlight a selection of compelling applications that have emerged over the past 5 years, illustrating how voltage imaging evolved from a proof of concept to being deployed to answer pending neuroscientific questions.

The striatum is a major cortical input site of the basal ganglia and plays a critical role in the control of orofacial movements such as licking. However, how striatal activity relates to the spatial features of licking behavior remains unclear. In this study, we examined whether neural activity in the striatal matrix and striosomal compartments is associated with the spatial position of a licking target during an operant task. Head-fixed male mice performed a licking task in which the target positions were varied across three spatial dimensions. Using fiber photometry in Calb1-IRES-Cre (n = 7) and Pdyn-IRES-Cre (n = 6) mice, we recorded calcium signals from matrix and striosomal neurons. Associations between neural activity, target position, and behavioral variables were quantified using linear mixed-effects modeling with cross-validation. Matrix activity prior to the first detected lick was associated with reaction time and the dorsal-ventral target position. During licking, matrix activity was associated with the anterior-posterior and medial-lateral positions, independent of reaction time and lick count, whereas striosomal activity was associated with the dorsal-ventral position. These associations were correlational and differed in strength. The association between matrix activity and the anterior-posterior and medial-lateral positions was the most robust. The present findings are limited to male mice and to the hemisphere ipsilateral to the spout.

Diabetic foot infection (DFI) significantly increases the risks of hospitalization and amputation, with biofilm infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Escherichia coli (CREC) being key drivers of treatment failure. Here, we analyzed MRSA/CREC biofilm-infected ulcer tissues from patients using proteomics and metabolomics. Compared with nonhealing tissues, healed tissues exhibit activation of low-density lipoprotein receptor (LDLR)-mediated low-density lipoprotein cholesterol (LDL-C) endocytosis and increased free fatty acid production; thus, we hypothesize a potential countermeasure against biofilms. However, the oxidative instability of free fatty acids limits their therapeutic use. Building on our findings demonstrating the potent anti-MRSA/CREC activity of rhein and its synergy with Ag⁺, we developed an injectable hydrogel for sustained codelivery of both agents. This formulation outperforms Ag⁺ monotherapy, accelerating wound closure in biofilm-infected diabetic wounds. Mechanistically, rhein binds to LDLR, upregulates its expression, and enhances the LDL-C endocytosis pathway in vascular endothelial cells to generate more free fatty acids. Among these, eicosapentaenoic acid (EPA) is identified as the most critical free fatty acid that promotes healing, as it inhibits biofilm formation and synergizes with Ag⁺ to exert antibacterial and pro-healing effects. In summary, this study identifies endogenous host lipid metabolites as "metabolic antibiotics" and establishes a synergistic therapeutic strategy that concurrently suppresses biofilm formation, inhibits planktonic bacteria, alleviates inflammation, and promotes tissue repair in drug-resistant biofilm-infected diabetic wounds.