Publications by authors named "Yan Jiao Wu"

Effective psychotherapy of post-traumatic stress disorder (PTSD) remains challenging owing to the fragile nature of fear extinction, for which the ventral hippocampal CA1 (vCA1) region is considered as a central hub. However, neither the core pathway nor the cellular mechanisms involved in implementing extinction are known. Here, we unveil a direct pathway, where layer 2a fan cells in the lateral entorhinal cortex (LEC) target parvalbumin-expressing interneurons (PV-INs) in the vCA1 region to propel low-gamma-band synchronization of the LEC-vCA1 activity during extinction learning.

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Chronic itch often clinically coexists with anxiety symptoms, creating a vicious cycle of itch-anxiety comorbidities that are difficult to treat. However, the neuronal circuit mechanisms underlying the comorbidity of anxiety in chronic itch remain elusive. Here, we report anxiety-like behaviors in mouse models of chronic itch and identify γ-aminobutyric acid-releasing (GABAergic) neurons in the lateral septum (LS) as the key player in chronic itch-induced anxiety.

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Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors.

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Article Synopsis
  • Homeostatic synaptic scaling adjusts synaptic strength in response to prolonged changes in neuronal activity and is linked to neuropsychiatric disorders.
  • Sustained high levels of GABA due to GAT1 deletion or inhibition lead to increased synaptic strength in corticostriatal pathways, causing hyperactivity in locomotion.
  • The study indicates that restoring the function of certain receptors can mitigate these effects, suggesting potential therapeutic strategies for addressing locomotor issues associated with GAT1 deficiency.
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  • Threat and extinction memories are vital for survival in changing environments, encoded by different neuron ensembles in the brain, specifically within the insular cortex (IC).
  • Research using male mice revealed two distinct neuron subpopulations in the IC that target the central amygdala (CeA) for fear memory and the nucleus accumbens (NAc) for extinction memory, highlighting how intracortical inhibition influences which memory type emerges.
  • The study also found that IC-NAc neurons receive inputs from the orbitofrontal cortex (OFC), suggesting that this area enhances extinction memory, illustrating the IC's role in distinguishing between fear and extinction memories with help from the OFC.
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  • - Fear extinction can help control learned fear responses, but often fails, leading to a return of the original fear due to forgetting of the extinction memory.
  • - Researchers found that specific neurons related to fear extinction memory are located in the medial prefrontal cortex, basolateral amygdala, and ventral hippocampus, and they work together in a directional way to help retrieve extinction memories.
  • - When fear returns, the connections for retrieving extinction memories become less accessible, but further extinction training or certain experimental techniques can restore these connections and prevent the fear from coming back.
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  • Synaptic associativity, a concept from Hebbian plasticity, plays a crucial role in how associations are formed and influence learning, particularly concerning fear memories.
  • Researchers discovered that fear renewal—where extinguished fear responses can come back—depends on the synaptic connections between the auditory cortex and the ventral hippocampus acting on the lateral amygdala.
  • Inactivating these connections prevents fear renewal, while stimulating them can trigger the same response, indicating that the link between these brain regions is essential for the resurgence of fear memories.
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The photo-manipulation of bioactive molecules provides unique advantages due to the high temporal and spatial precision of light. The first visible-light uncaging reaction by photocatalytic deboronative hydroxylation in live cells is now demonstrated. Using Fluorescein and Rhodamine derivatives as photocatalysts and ascorbates as reductants, transient hydrogen peroxides were generated from molecular oxygen to uncage phenol, alcohol, and amine functional groups on bioactive molecules in bacteria and mammalian cells, including neurons.

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Extinction of conditioned fear necessitates the dynamic involvement of hippocampus, medial prefrontal cortex (mPFC), and basolateral amygdala (BLA), but key molecular players that regulate these circuits to achieve fear extinction remain largely unknown. Here, we report that acid-sensing ion channel 1a (ASIC1a) is a crucial molecular regulator of fear extinction, and that this function requires ASIC1a in ventral hippocampus (vHPC), but not dorsal hippocampus, mPFC, or BLA. While genetic disruption or pharmacological inhibition of ASIC1a in vHPC attenuated the extinction of conditioned fear, overexpression of the channel in this area promoted fear extinction.

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Article Synopsis
  • ASIC1a, an ion channel found in the brain, is crucial for motor skills and learning related to the striatum, a part of the basal ganglia.
  • * Research showed that the absence of ASIC1a in mice led to structural issues in neurons and reduced function of key receptors, impacting motor coordination and procedural learning.
  • * The deficits seen in mice without ASIC1a were linked to decreased activation of specific proteins (CaMKII and ERKs), but could be corrected by restoring ASIC1a or CaMKII in the striatum.
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An imbalance between neuronal excitation and inhibition represents a core feature in multiple neuropsychiatry disorders, necessitating the development of novel strategies to calibrate the excitatory-inhibitory balance of therapeutics. Here we identify a natural compound quercetin that reduces prefrontal cortical GABAergic transmission and alleviates the hyperactivity induced by glutamatergic N-methyl-d-aspartate receptor antagonist MK-801. Quercetin markedly reduced the GABA-activated currents in a noncompetitive manner in cultured cortical neurons, and moderately inhibited spontaneous and electrically-evoked GABAergic inhibitory postsynaptic current in mouse prefrontal cortical slices.

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  • The study investigates the role of ASIC1a in synaptic plasticity in the mouse hippocampus, finding that its deletion or blockage reduces long-term potentiation (LTP) probability but does not completely eliminate it.
  • ASIC1a's influence is more pronounced in LTP induced by high-frequency stimulations, while it does not impact long-term depression induced by low-frequency stimulation.
  • The research reveals that ASIC1a enhances NMDA receptor function among other mechanisms in LTP, contributing to a broader understanding of synaptic plasticity in the brain.
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  • A molecularly imprinted polymer (MIP) was created to specifically bind to chlorsulfuron, a herbicide, using various chemical components through a specific synthesis method.
  • The binding efficiency of the MIP for chlorsulfuron was tested through equilibrium adsorption experiments, demonstrating a strong affinity for the target molecule.
  • An optimized solid-phase extraction (SPE) method using the MIP was established to effectively capture and analyze chlorsulfuron residue in water, soils, and wheat plants, resulting in high recovery rates in various samples.
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A new and efficient analytic methodology based on cloud point extraction (CPE) was developed for determination of pesticide residues of metsulfuron-methyl (MSM), chlorsulfuron (CS), and bensulfuron-methyl (BSM) in water, soil, and rice grain by high-performance liquid chromatography (HPLC). Multiple experimental conditions that affected CPE efficiency-including surfactant type and concentration, equilibration temperature and duration, ionic strength, and solution pH were identified. CPE conditions were optimized as follows: 1.

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