Neuron-astrocyte Coupling in Lateral Habenula Mediates Depressive-like Behaviors DOI Open Access

Qianqian Xin,

Junying Wang,

Jing Zheng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 3, 2024

Summary The lateral habenular (LHb) neurons and astrocytes have been strongly implicated in depression etiology but it was not clear how the two dynamically interact during onset. Here, using multi-brain-region calcium photometry recording freely-moving mice, we discover that stress induces a unique, bimodal neuronal response most rapid astrocytic LHb. LHb requires α 1A -adrenergic receptor, depends on recurrent neural network between locus coeruleus (LC). Through gliotransmitter glutamate ATP/Adenosine, mediate second-wave activation of local as well release norepinephrine (NE). Activation or inhibition signaling facilitates prevents stress-induced depressive-like behaviors respectively. These results identify positive feedback loop LHb-LC axis, with being critical relay. identification this prominent neuron-glia interaction may shed light management prevention.

Language: Английский

Projection-targeted photopharmacology reveals distinct anxiolytic roles for presynaptic mGluR2 in prefrontal- and insula-amygdala synapses DOI
Hermany Munguba,

Ipsit Srivastava,

Vanessa A. Gutzeit

et al.

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Binding of HCN channels to GABAB receptors in dopamine neurons of the VTA limits synaptic inhibition and prevents the development of anxiety DOI Creative Commons

Enrique Pérez‐Garci,

Kateryna Pysanenko, Giorgio Rizzi

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106831 - 106831

Published: Feb. 1, 2025

During GABAergic synaptic transmission, G protein-coupled GABAB receptors (GBRs) activate K+ channels that prolong the duration of inhibitory postsynaptic potentials (IPSPs). We now show KCTD16, an auxiliary GBR subunit, anchors hyperpolarization-activated cyclic nucleotide-gated (HCN) containing HCN2/HCN3 subunits to GBRs. In dopamine neurons VTA (DAVTA neurons), this interaction facilitates activation HCN via hyperpolarization during IPSPs, counteracting GBR-mediated late phase these IPSPs. Consequently, disruption GBR/HCN complex in KCTD16-/- mice leads prolonged optogenetic inhibition DAVTA neuron firing. exhibit increased anxiety-like behavior response stress - a replicated by CRISPR/Cas9-mediated KCTD16 ablation or intra-VTA infusion antagonist wild-type mice. Our findings support retention at synapses GBRs provides negative feedback mechanism restricts IPSP and mitigates development anxiety.

Language: Английский

Citations

0
Genome sequencing and identification of candidate variants for a red/black color polymorphism in tilapia (Oreochromis spp.) DOI Creative Commons
Kristen A. Behrens,

Aimee H. Danley,

Soumya Jailwala

et al.

Aquaculture, Journal Year: 2025, Volume and Issue: unknown, P. 742411 - 742411

Published: March 1, 2025

Language: Английский

Citations

0
Red and far-red cleavable fluorescent dyes for self-labelling enzyme protein tagging and interrogation of GPCR co-internalization DOI Creative Commons
Kilian Roßmann,

Ramona Birke,

Joshua Levitz

et al.

RSC Chemical Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Post-labelling cleavable substrates for self-labelling protein tags, such as SNAP- and Halo-tags, can be used to study cell surface receptor trafficking events by stripping dyes from non-internalized pools. Since the complexity of biology requires use multiple orthogonal approaches simultaneously probe pools, we report development four membrane impermeable probes that covalently bind either or Halo-tag in red far-red range. These molecules bear a disulfide bond release using reducing agent sodium 2-mercaptoethane sulfonate (MESNA). As such, our approach allows simultaneous visualization internalized proteins two colors which showcase G protein-coupled receptors. We this detect group II metabotropic glutamate (mGluRs), homo- heterodimers, reveal unidirectional crosstalk between co-expressed glucagon-like peptide 1 (GLP1R) glucose-dependent insulinotropic polypeptide receptors (GIPR). In these applications, translate method both high resolution imaging quantitative, throughput assays, demonstrating value wide range applications.

Language: Английский

Citations

2
Non-canonical adrenergic neuromodulation of motoneuron intrinsic excitability through β-receptors in wild-type and ALS mice DOI Creative Commons
Stefano Antonucci, Guillaume Caron,

Natalie Dikwella

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 29, 2024

Abstract Homeostatic feedback loops are essential to stabilize the activity of neurons and neuronal networks. It has been hypothesized that, in context Amyotrophic Lateral Sclerosis (ALS), an excessive gain might hyper- or hypo-excite motoneurons (MNs) contribute pathogenesis. Here, we investigated how neuromodulation MN intrinsic properties is homeostatically controlled presymptomatic adult SOD1(G93A) mice age-matched control WT mice. First, determined that β2 β3-adrenergic receptors, which Gs-coupled receptors subject tight robust loops, specifically expressed spinal MNs both SOD1 at P45. We then demonstrated these elicit a so-far overlooked firing excitability MNs. These electrical regulated following receptor engagement, triggers ion channel transcriptional changes downregulates those receptors. homeostatic feedbacks not dysregulated mice, they set upon β-adrenergic neuromodulation.

Language: Английский

Citations

1
Neuron-astrocyte Coupling in Lateral Habenula Mediates Depressive-like Behaviors DOI Open Access

Qianqian Xin,

Junying Wang,

Jing Zheng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 3, 2024

Summary The lateral habenular (LHb) neurons and astrocytes have been strongly implicated in depression etiology but it was not clear how the two dynamically interact during onset. Here, using multi-brain-region calcium photometry recording freely-moving mice, we discover that stress induces a unique, bimodal neuronal response most rapid astrocytic LHb. LHb requires α 1A -adrenergic receptor, depends on recurrent neural network between locus coeruleus (LC). Through gliotransmitter glutamate ATP/Adenosine, mediate second-wave activation of local as well release norepinephrine (NE). Activation or inhibition signaling facilitates prevents stress-induced depressive-like behaviors respectively. These results identify positive feedback loop LHb-LC axis, with being critical relay. identification this prominent neuron-glia interaction may shed light management prevention.

Language: Английский

Citations

1