Biology subjects

Dumrongprechachan, V.

Publications and source records attributed to Dumrongprechachan, V..

5 recordsLinked to original sources

bioRxiv2026

Proteomic profiling across early postnatal development of midbrain dopamine axons innervating the dorsal striatum

Precise wiring and tuning of dopamine axons in the brain is crucial for normal development of basal ganglia circuits. This process takes place both pre and postnatally, with early postnatal windows reflecting important periods of terminal maturation. Protein expression and precise localization are vital to this process, underlying changes in axon structure and function. Yet, technical hurdles have prohibited mapping protein expression and localization as dopamine axons mature to form functional release sites. Here we employ targeted proximity labeling in midbrain dopamine neurons and track isolated distal axonal proteins in the striatum across development, from the neonatal period through adolescence. Our approach enabled high-precision evaluation of the axonal proteome, supported by a combination of Cre-recombinase based restriction and spatial separation. We map co-varying subpopulations of axonal proteins differentially expressed across development. Microtubule-associated proteins decreased over time, revealing temporal dynamics of dopaminergic axon stabilization at the proteomic level. Conversely, proteins supporting coordinated action potential firing increased over time, likely contributing to the characteristic tonic firing of dopamine neurons emerging over development. Intersecting our findings with recent GWAS of psychiatric and neurological disorders provided functional confirmation of disease and disorder risk. This analysis highlighted early expression and localization of risk gene products, providing spatial-temporal points of convergence for disease-associated variants specifically to the initial stages of postnatal neurodevelopment of dopamine neurons. Together, these findings provide the essential grounding for understanding postnatal dopaminergic axon development and contextualize neurodevelopmental functions for numerous risk gene products.

neuroscience↗

bioRxiv2022

Dynamic proteomic and phosphoproteomic atlas of corticostriatal axon neurodevelopment

Mammalian axonal development begins in embryonic stages and continues postnatally. After birth, axonal proteomic landscape changes rapidly, coordinated by transcription, protein turnover, and post-translational modifications. Comprehensive profiling of axonal proteomes across neurodevelopment is limited, with most studies lacking cell-type and neural circuit specificity, resulting in substantial information loss. We create a Cre-dependent APEX2 reporter mouse line and map cell-type specific proteome of corticostriatal projections across postnatal development. We synthesize analysis frameworks to define temporal patterns of axonal proteome and phosphoproteome, identifying co-regulated proteins and phosphorylations associated with genetic risk for human brain disorders. We discover proline-directed kinases as major developmental regulators. APEX2 transgenic reporter proximity labeling offers flexible strategies for subcellular proteomics with cell type specificity in early neurodevelopment, a critical period for neuropsychiatric disease.

neuroscience↗

bioRxiv2021

Peptidergic modulation of fear responses by the Edinger-Westphal nucleus

Many neuronal populations that release fast-acting excitatory and inhibitory neurotransmitters in the brain also contain slower acting neuropeptides. These facultative peptidergic cell types are common, but it remains uncertain whether obligate peptidergic neurons exist. Our fluorescence in situ hybridization, genetically-targeted electron microscopy, and electrophysiological characterization data strongly suggest that neurons of the non-cholinergic, centrally-projecting Edinger-Westphal nucleus in mice are fundamentally obligately peptidergic. We further show, using fiber photometry, monosynaptic retrograde tracing, anterograde projection mapping, and a battery of behavioral assays, that this peptidergic population both promotes fear responses and analgesia and activates in response to loss of motor control and pain. Together, these findings elucidate an integrative, ethologically relevant function for the Edinger-Westphal nucleus and functionally align the nucleus with the periaqueductal gray, where it resides. This work advances our understanding of the peptidergic modulation of fear and provides a framework for future investigations of putative obligate peptidergic systems.

neuroscience↗

bioRxiv2021

Cell type and subcellular compartment specific APEX2 proximity labeling proteomics in the mouse brain

The vertebrate brain consists of diverse neuronal types, classified by distinct anatomy and function, along with divergent transcriptomes and proteomes. Defining the cell type-specific neuroproteome is important for understanding the development and functional organization of neural circuits. This task remains challenging in complex tissue, due to suboptimal protein isolation techniques that often result in loss of cell-type specific information and incomplete capture of subcellular compartments. Here, we develop a genetically targeted proximity labeling approach to identify cell-type specific subcellular proteome in the mouse brain. Using adeno- associated viral transduction, we express subcellular-localized APEX2 to map the proteome of the nucleus, cytosol, and cell membrane of Drd1 receptor-positive striatal neurons. We show that each APEX2 construct can differentially and rapidly biotinylate proteins in situ across various subcellular compartments, confirmed by imaging, electron microscopy, and mass spectrometry. This method enables flexible, cell-type specific quantitative profiling of subcellular proteome in the mouse brain.

neuroscience↗

bioRxiv2020

Ketamine restores escape behavior by re-engaging dopamine systems to drive cortical spinogenesis

Escaping aversive stimuli is essential for complex organisms, but prolonged exposure to stress leads to maladaptive learning. Stress alters plasticity, neuromodulatory signaling, and neuronal activity in distributed networks, yet the field lacks a unifying framework for its varied consequences. Here we describe neuromodulatory and plasticity changes following aversive learning by using a learned helplessness paradigm, where ketamine restores escape behavior. Dopaminergic neuron activity in the ventral tegmental area systematically varies across learning, correlating with future sensitivity to ketamine treatment. Ketamines effects are blocked by chemogenetic inhibition of dopamine signaling and mimicked by optogenetic activation. We use 2-photon glutamate uncaging/imaging to interrogate structural plasticity in medial prefrontal cortex, revealing that dendritic spinogenesis on pyramidal neurons is both regulated by aversive experience and recovered by ketamine in a dopamine-dependent manner. Together, these data describe recurrent circuits that causally link neuromodulatory dynamics, aversive learning, and plasticity enhancements driven by a therapeutically promising antidepressant.

neuroscience↗