Medial prefrontal cortex activity precedes dorsomedial striatum in need for change during history-based flexible behavior

Being cognitively flexible is vital for survival, and its impairment is central to many psychiatric and neurodegenerative disorders. Both the medial prefrontal cortex (mPFC) and dorsomedial striatum (DMS) are essential for cognitive flexibility, but their specific roles—particularly which region first detects and encodes environmental changes—remain debated. Using head-restrained mice in a choice task based on […]

Genetically encoded calcium (Ca2+) indicators (GECIs) are essential tools for monitoring neuronal activity, but the performance of red fluorescent GECIs has remained limited. In particular, many red indicators are relatively dim, produce low signal-to-noise ratios and can undergo unwanted photoswitching when exposed to blue light, restricting their use in all-optical experiments that combine imaging with […]

Brain-resident macrophages, microglia, have been proposed to have an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that several neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse that lacks microglia (Csf1r∆FIRE/∆FIRE), we find that intrinsic properties, synapse number and synaptic maturation […]

The progressive loss of cerebral white matter during aging contributes to cognitive decline, but whether reduced blood flow is a cause or a consequence remains debatable. Using deep multi-photon imaging in mice, we examined microvascular networks perfusing myelinated tissues in cortical layer 6 and the corpus callosum. We identified sparse, wide-reaching venules, termed principal cortical […]

Restoring retinal pigment epithelium (RPE) cells is crucial for treating retinal degenerative (RD) diseases, with chemical reprogramming offering a transformative, scalable solution. However, identifying key chemical compounds for generating functional RPE cells from somatic cells remains challenging. Here, we present a two-step chemical reprogramming strategy to convert fibroblasts into functional chemical induced RPE (ciRPE) cells. […]

ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome is a rare genetic disease caused by variants in alpha-kinase 1 (ALPK1) resulting in downstream pro-inflammatory signaling mediated by the TIFA/TRAF6/NF-κB pathway. Here, we report the design of an ALPK1 inhibitor, DF-003, with pharmacokinetic properties suitable for daily oral dosing. In biochemical assays, DF-003 […]

Brain-resident macrophages, microglia, have been proposed to have an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that several neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse that lacks microglia (Csf1r∆FIRE/∆FIRE), we find that intrinsic properties, synapse number and synaptic maturation […]

Being able to switch from established choices to new alternatives when conditions change – behavioral flexibility – is essential for survival. Cholinergic signaling in the striatum contributes to such flexible behavior, yet the timing and spatial organization of acetylcholine release during contingency changes remain unclear, limiting conceptual understanding of its role in behavioral flexibility. Using […]

Neurons in prefrontal cortex (PF) represent mnemonic information about current goals until the action can be selected and executed. However, the neuronal dynamics underlying the transition from goal into specific actions are poorly understood. Here, we show that the goal-coding PF network is dynamically reconfigured from mnemonic to action selection states and that such reconfiguration […]

Under conditions of scarce food availability and cool ambient temperature, the mouse (Mus Musculus) enters into torpor, a state of transient metabolic suppression mediated in part by the autonomic nervous system. Hypothalamic orexins are involved in the coordination of behaviors and autonomic function. We tested whether orexins are necessary for the coordinated changes in physiological […]