Probing the spatiotemporal release dynamics of multiple neurochemicals simultaneously in vivo is essential for understanding the molecular basis of brain function and behavior. Microdialysis enables multiplexed neurochemical analysis when combined with advanced molecular tools such as mass spectrometry, but existing microdialysis probes typically exhibit low recovery rates and provide temporal resolution of several minutes, which […]

Noradrenergic neurons in the locus coeruleus (LC) shape sensory processing, yet how LC activity influences population taste coding remains unclear. Using optogenetic LC activation with miniscope imaging in the gustatory cortex (GC), we examined LC modulation of multiple taste attributes. Phasic LC activation strengthens correlations between neuronal responses and palatability and expands the dynamic range […]

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in MECP2. Disordered breathing is a hallmark feature of RTT that negatively impacts quality of life and can be life-threatening. Despite this, the mechanisms underlying disordered breathing in RTT are poorly understood. Although RTT is primarily considered a central nervous system disorder, we found that […]

In the Drosophila antenna, olfactory sensilla are the fundamental unit of odor detection and processing. Sensilla house one to four olfactory neurons enwrapped by three distinct support cells: thecogen, trichogen, and tormogen cells. While olfactory neurons and their odor receptors have been extensively studied in Drosophila, and increasingly in other insect species, much less is […]

Synapse formation and function are coordinated spatially and temporally by a host of synaptic proteins that regulate neuronal signaling, synapse specificity, and plasticity, many of which are implicated in neuropsychiatric disorders. Many members of the C1q/TNF superfamily function as synaptic organizers, shaping synapse assembly and maintenance. Among them, C1QL3 plays a putative role in trans-synaptic […]

Reliable 3D reconstruction of tissue architecture from sequential 2D multiplex images is challenging due to the noise and distortions introduced by ultrathin (50 nm) slicing and complex alignment procedures. Conventional cell tracking methods often fail under such conditions, resulting in inaccurate linkage of cells across sections. To bridge this gap, we propose a Bayesian Transformer […]

Acetylcholine (ACh) affects both the intrinsic properties of individual neurons and the oscillatory tendencies of cortical microcircuits by modulating the muscarinic-receptor gated m-current. ACh concentrations have historically been assumed to vary exclusively over long (supra-second) neuromodulatory timescales, conventionally simplified in silico as a set and constant modulatory tone. However, contemporary experimental studies show cortical ACh […]

The lateral hypothalamic area (LHA) is well-known for its conserved role in modulating and driving many forms of innate behaviors, yet the cellular diversity underlying these functions remains incompletely understood. Although neurons expressing the neuropeptide thyrotropin-releasing hormone (TRH) in the hypothalamic paraventricular nucleus have been well-characterized for their hypophysiotropic functions and role in metabolism and […]

Minor intron-containing genes (MIGs), which require the minor spliceosome (MiS) for their splicing, are highly represented among genes involved in mouse spermatogenesis. Leveraging gene- and intron-level ortholog data, we show that conservation of these genes as MIGs is particularly strong in chordates but not in other species groups, suggesting lineage-specific changes to their splicing regulation. […]

Brain systems mediating responses to previously encountered threats provide critical survival functions. Fear memory and extinction are underpinned by neural representations in the basolateral amygdala (BLA)^(1-7), but the contribution of non-neuronal cells, including astrocytes, to these processes remains unresolved. Here, using in vivo calcium (Ca^(2+)) imaging and causal astrocyte manipulations, we find that BLA astrocytes […]

Three-dimensional genome organization influences splicing, yet how introns, particularly rare introns, are arranged within the nucleus and whether this organization contributes to splicing have not been fully explored. We mapped the organization of six intron classes, major, minor, minor-like, hybrid, major-like, and non-canonical, across four human cell lines using Hi-C, TSA-seq, and DamID-seq. Minor intron-containing […]

KCNQ2 potassium channel variants are linked to developmental and epileptic encephalopathy (DEE). However, the mechanisms by which pathogenic variants, especially those outside known hotspots, such as the S4-S5 linker, lead to disease remain unknown. Here, we examined the H228R variant, a pathogenic mutation in the S4-S5 linker associated with DEE. We tested whether H228R induces […]