Biology subjects

Niu, L.-G.

Publications and source records attributed to Niu, L.-G..

5 recordsLinked to original sources

bioRxiv2025

Long-term editing of brain circuits in mice using an engineered electrical synapse

Electrical signaling across distinct populations of brain cells underpins cognitive and emotional function; however, approaches that selectively regulate electrical signaling between two cellular components of a mammalian neural circuit remain sparse. Here, we engineered an electrical synapse composed of two connexin proteins found in Morone americana (white perch fish) - connexin34.7 and connexin35 - to accomplish mammalian circuit modulation. By exploiting protein mutagenesis, devising a new in vitro system for assaying connexin hemichannel docking, and performing computational modeling of hemichannel interactions, we uncovered a structural motif that contributes to electrical synapse formation. Targeting these motifs, we designed connexin34.7 and connexin35 hemichannels that dock with each other to form an electrical synapse, but not with other major connexins expressed in the mammalian central nervous system. We validated this electrical synapse in vivo using C. elegans and mice, demonstrating that it can strengthen communication across neural circuits composed of pairs of distinct cell types and modify behavior accordingly. Thus, we establish Long-term integration of Circuits using connexins (LinCx) for precision circuit-editing in mammals.

neuroscience↗

bioRxiv2025

Melatonin Enhances Sleep via MT1-Driven Activation of Slo1 in Suprachiasmatic Nucleus Neurons

Melatonin promotes sleep through mechanisms that have remained elusive. Here, we identify a molecular pathway by which melatonin promotes sleep by activating BK channels (Slo1) via MT1 receptors in the suprachiasmatic nucleus (SCN), the brains master circadian clock. In melatonin-proficient CBA/CaJ mice, knockout of either MT1 or Slo1 reduces REM and NREM sleep during the rest phase (daytime), accompanied by prolonged action potentials and diminished afterhyperpolarization in SCN neurons. These electrophysiological and behavioral changes are minimal during the active phase (nighttime). Strikingly, Slo1 expression in the SCN peaks during the daytime, contrary to previous reports, but aligning with its sleep-promoting function. Slo1, but not MT1, deletion also triggers spontaneous seizures, highlighting broader functions beyond circadian control. Structural mapping identifies critical domains mediating MT1-Slo1 coupling. Together, these findings position the MT1-Slo1 signaling axis as a core circadian mechanism linking melatonin to sleep regulation and a potential therapeutic target for sleep disorders.

neuroscience↗

bioRxiv2023

Specific configurations of electrical synapses filter sensory information to drive choices in behavior

Synaptic configurations in precisely wired circuits underpin how sensory information is processed by the nervous system, and the emerging animal behavior. This is best understood for chemical synapses, but far less is known about how electrical synaptic configurations modulate, in vivo and in specific neurons, sensory information processing and context-specific behaviors. We discovered that INX-1, a gap junction protein that forms electrical synapses, is required to deploy context-specific behavioral strategies during C. elegans thermotaxis behavior. INX-1 couples two bilaterally symmetric interneurons, and this configuration is required for the integration of sensory information during migration of animals across temperature gradients. In inx-1 mutants, uncoupled interneurons display increased excitability and responses to subthreshold temperature stimuli, resulting in abnormally longer run durations and context-irrelevant tracking of isotherms. Our study uncovers a conserved configuration of electrical synapses that, by increasing neuronal capacitance, enables differential processing of sensory information and the deployment of context-specific behavioral strategies. One-Sentence SummaryCoupling of interneurons by electrical synapses reduces membrane resistance and filters sensory inputs to guide sensory-dependent behavioral choices.

neuroscience↗

bioRxiv2022

Channel-independent function of UNC-9/INX in spatial arrangement of GABAergic synapses in C. elegans

Precise synaptic connection of neurons with their targets is essential for the proper functioning of the nervous system. A plethora of signaling pathways act in concert to mediate the precise spatial arrangement of synaptic connections. Here we show a novel role for a gap junction protein in controlling tiled synaptic arrangement in the GABAergic motor neurons in C. elegans, in which their axons and synapses overlap minimally with their neighboring neurons within the same class. We found that while EGL-20/Wnt controls axonal tiling, their presynaptic tiling is mediated by a gap junction protein UNC-9/Innexin, that is localized at the presynaptic tiling border between neighboring DD neurons. Strikingly, the gap junction channel activity of UNC-9 is dispensable for its function in controlling tiled presynaptic patterning. While gap junctions are crucial for the proper functioning of the nervous system as channels, our finding uncovered the novel channel-independent role of UNC-9 in synapse patterning.

neuroscience↗

bioRxiv2019

Slo2 potassium channel function depends on a SCYL1 protein

Slo2 potassium channels play important roles in neuronal function, and their mutations in humans cause epilepsies and cognitive defects. However, little is known how Slo2 function is regulated by other proteins. Here we found that the function of C. elegans Slo2 (SLO-2) depends on adr-1, a gene important to RNA editing. However, slo-2 transcripts have no detectable RNA editing events and exhibit similar expression levels in wild type and adr-1 mutants. In contrast, mRNA level of scyl-1, which encodes an orthologue of mammalian SCYL1, is greatly reduced in adr-1 mutants due to deficient RNA editing at a single adenosine in its 3-UTR. SCYL-1 physically interacts with SLO-2 in neurons. Single-channel open probability of SLO-2 in neurons is reduced by [~]50% in scyl-1 knockout whereas that of human Slo2.2/Slack is doubled by SCYL1 in a heterologous expression system. These results suggest that SCYL-1/SCYL1 is an evolutionarily conserved regulator of Slo2 channels.

neuroscience↗