Biology subjects

Min, M.-Y.

Publications and source records attributed to Min, M.-Y..

4 recordsLinked to original sources

bioRxiv2026

Mild and Reversible Proprioception Perturbation Suggests Causal Biomechanics for Memory-Dependent Spatial Behavior in Mice

The neural system at the periphery is a frontline for embodied cognition, yet an acute, mild perturbation to dissect functional causality is hard to achieve. Peripheral neural processes and the central nervous system may work in concert to generate sophisticated representations regarding self and environments in the brain. This hypothesis, together with the underlying mechanisms, is particularly difficult to test for certain sensory inputs due to the lack of reversible manipulation techniques. Long postulated as a component for path integration, proprioception is one of such modalities. In this study, we developed a murine experimental system to manipulate proprioceptive inputs during memory-dependent localization task (which required precise operant-conditioned licks) in spatial virtual reality (VR). Through bioluminescent optogenetics (luminopsin) selectively expressed in the parvalbumin-positive neurons of the dorsal root ganglia in mice, proprioceptive processing was compromised directly from the periphery to bypass the bottleneck of specific central targeting, which results from the lack of anatomically or genetically dedicated proprioceptive circuits in the brain. In-vivo IVIS imaging and behavior suggested the effects of luminopsin last for roughly 20 minutes. While mice exhibited normal performance in tasks relying on gross motor skills, they showed subtle deficits in challenging spatial tasks that required integration of past movements. These observations support a task-specific role for proprioception, and demonstrate a potential of chemogenetics-like, rapidly reversible strategies for characterizing peripherally defined sensory contribution to spatial cognition. Future work will optimize this approach; for instance, to activate opsins by light with millisecond precision. To our knowledge, this is a first causal demonstration for acute participation of proprioception in path-integration biomechanics, enabling the first temporally defined method for mild perturbation of path-integration mechanisms.

neuroscience↗

bioRxiv2025

Pharmacological and Physiological Characteristics of Synaptic Transmissions from the Medial Prefrontal Cortex onto Noradrenergic Neurons and Their Presynaptic Neurons in the Mouse Locus Coeruleus

The locus coeruleus (LC) is the primary source of norepinephrine in the brain and is known to modulate brain-wide arousal state. Recent evidence suggests that it also regulates immediate attentional responses by resetting related cortical networks to optimize behavioral outcomes. Cortical regions of high cognitive function, such as the medial prefrontal cortex (mPFC), are theorized to directly influence LC output for the purpose of behavioral regulation. However, the available evidence is insufficient to provide a comprehensive understanding of the underlying mechanisms and properties. To provide further comprehensive data on this issue, we combined ex vivo whole-cell recording with an optogenetic approach to study the synaptic transmission of mPFC inputs to LC neurons, including noradrenergic (NA) neurons and GABAergic neurons presynaptic to them (preLC neurons). Our findings indicate that the mPFC exhibits monosynaptic connections with both NA and GABAergic preLC neurons. These synaptic connections demonstrate cell-type-specific disparities in glutamate release properties. In comparison to those on GABAergic preLC neurons, the mPFC fibers synapsing on LC-NA exhibit a lower release probability (higher paired-pulse ratio) and demonstrate a presynaptic enhancement of glutamate release efficacy during behavior. The features of simultaneous connections onto LC-NA and GABAergic preLC neurons, which exhibit cell-type-specific differences in plastic function of the transmitter release, enable the mPFC to effectively multiplex information to the LC for the adaptive regulation of behavior.

neuroscience↗

bioRxiv2025

Axon collateral pattern of a sparse locus coeruleus norepinephrine neuron in mouse cerebral cortex.

The locus coeruleus (LC) contains predominantly norepinephrine (NE) neurons that project widely throughout the brain. The LC plays a critical role in controlling behavior, particularly arousal. Historically, it was thought that the LC-NE system performed its behavioral control function by uniformly releasing NE throughout most brain regions. However, recent evidence suggests that the LCs cortical projections are organized into modules, which allows for the coordination of diverse, and sometimes opposing, functions such as fear memory formation and extinction. Nevertheless, many details remain unclear and require data from the axon collaterals of sparse neurons. We modified a viral tracing protocol using a dual-recombinase system to trace the axonal collaterals of sparse LC neurons projecting to the cingulate cortex (CgC). Our results show that even a small number of LC neurons have broad cortical projections, though the pattern is not uniform. Centered-log ratio transformation of NE fiber distribution across the cortex and hippocampus reveals a few preferential target areas (PTAs) of the labeled LC-NE neurons axonal projections. The summed NE fiber length in these defined PTs is enriched relative to the geometric mean of all other cortical and hippocampal regions where NE fibers were detected. Notably, the defined PTAs--including the rostral splenial cortex, dorsal hippocampus, somatosensory cortex, and CgC (the retrograde viral labeling injection site)--are functionally related to navigation. These results demonstrate that LC-NE neurons are organized into distinct projection modules, each comprising a small number of neurons with functionally correlated major cortical targets.

neuroscience↗

bioRxiv2024

Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors

The brainstem cell group, locus coeruleus (LC), is present across vertebrates and influences cardiorespiratory, metabolic, immune, and cognitive functions by activating in two putatively distinct firing patterns. Yet, the degree to which the LC firing rates and patterns are homogenous across species has never been assessed due to inherently limited sample sizes. To remedy this, we pooled cross-species data from 20 laboratories to show that firing rates differ across species and are modulated by sex, age, and type of in vitro or in vivo preparation. Contrary to the prevailing dual-mode firing pattern schema, we observed patterns spread across a low-dimensional manifold, with subregions enriched for specific biological factors and neurodegenerative disease models. Our findings show considerable diversity in an ancestral vertebrate neuromodulatory system.

neuroscience↗