Biology subjects

Wang, K.-Y.

Publications and source records attributed to Wang, K.-Y..

5 recordsLinked to original sources

bioRxiv2026

Acetylcholine drives astrocytic JAK2-STAT3 signaling to modulate male-to-female approach behavior

Astrocytes are essential regulators of neural circuits and behavior, sensing synaptic activity and modulating plasticity through diverse intracellular mechanisms. However, the contribution of astrocyte transcription factor-based cascades, linking external stimuli to long-term transcriptional programs, is currently misunderstood. Here we show that the JAK2-STAT3 signaling plays a critical role in male-to-female social behavior. Hence, in male mice, exposure to estrus females rapidly and selectively induces STAT3 signaling in ventral hippocampal astrocytes. Surprisingly, this induction is not driven through canonical cytokine signaling but by septo-hippocampal cholinergic inputs acting through 7 nicotinic acetylcholine receptors (7nAChR). Astrocytic 7nAChR-JAK2-STAT3 signaling in turn modulates vCA1 pyramidal neuron activity and is required for context-appropriate male approach behavior. These findings reveal a previously unsuspected cellular pathway integrating neuromodulatory inputs and transcription factor-based signaling to shape male behavioral response depending on female receptivity.

neuroscience↗

bioRxiv2026

Sex-dependent involvement of lateral septum astrocytes in social fear: Role of oxytocin receptor signaling

Astrocytes are now widely recognized as important modulators of synaptic plasticity and socio-emotional behaviors. Recent studies highlight their involvement in anxiety- and depressive-like behaviors, particularly via oxytocin (OXT) signaling. While the specific contributions of astrocytes remain largely unexplored, the role of OXT receptor (OXTR) signaling in the lateral septum (LS) in regulating social fear expression has been well characterized. Here, we studied the differential contribution of astrocytic OXTR signaling using a social fear conditioning (SFC+) paradigm. We found the highest abundance of astrocytes, and especially of OXTR-expressing (OXTR+) astrocytes, within the caudal LC (LSc) compared to the rostral LS in both male and female mice. Interestingly, female mice displayed a significantly higher number of astrocytes and OXTR+ astrocytes in the LSc in comparison to males. However, social fear acquisition resulted in dynamic changes in LSc astrocytic morphology and calcium activity in male mice. Furthermore, we showed that pre-SFC acquisition pharmacology-induced loss of local astrocytic function facilitated the extinction of social fear in males. In support, astrocyte-specific OXTR knockdown in the LSc also facilitated social fear extinction in both males and females. Taken together, our study identifies OXTR-signaling in LSc astrocytes as a crucial component in the mechanisms underlying the regulation of social fear in a sex-dependent manner.

neuroscience↗

bioRxiv2024

Oxytocin Gαi signaling-induced amygdala astrocytes processes retraction shapes behavioral stress response

Anticipated reactions to stressful situations are vital for the survival and well-being of organisms, and abnormal reactions are involved in stress-related disorders. The neuropeptide oxytocin is a key modulator ensuring well-adapted stress responses. Oxytocin acts on both neurons and astrocytes, but the molecular and cellular mechanisms mediating stress response remain poorly understood. Here, we focus on the amygdala, a crucial hub that integrates and processes sensory information through oxytocin- dependent mechanisms. Using an acute stress paradigm in mice, genetic and pharmacological manipulations combined with proteomic, morphological, electrophysiological and behavioral approaches, we reveal that oxytocinergic modulation of the freezing response to stress is mediated by transient Gi-dependent retraction of astrocytic processes, followed by enhanced neuronal sensitivity to extracellular potassium in the amygdala. Our findings elucidate a pivotal role for astrocytes morphology- dependent modulation of brain circuits that is required for proper anticipated behavioral response to stressful situations.

neuroscience↗

bioRxiv2023

Inhibitory fear memory engram in the mouse central lateral amygdala

Engrams are cellular substrates of memory traces that have been identified in various brain areas, including the amygdala. Most engrams identified so far are formed by excitatory, glutamatergic neurons. However, little attention has been paid to defining GABAergic inhibitory engrams. Here, we report an inhibitory engram in the central lateral amygdala (CeL), a crucial area for Pavlovian fear conditioning. This engram is primarily composed of GABAergic somatostatin-expressing (SST+) and to a lesser extent of protein kinase C-{delta}-expressing [PKC-{delta}(+)] neurons. Fear memory is accompanied by a preferential enhancement of mIPSC frequency onto PKC-{delta}(+) neurons as well as a general increment of amplitude. Moreover, non-engram cells exhibit higher mIPSC frequency than engram cells. The inhibition of the CeL GABAergic engram disinhibits the activity of engram-targeted areas and increases selectively the encoded fear expression. Our data defines the behavioral function of an engram formed exclusively by GABAergic inhibitory neurons in the mammalian CNS.

neuroscience↗

bioRxiv2023

Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System

A causal relationship exists among the aging process, organ decay and dis-function, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termed Klf1K74R/K74R or Klf1(K74R), carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/ EKLF has been generated that possesses extended lifespan and healthy characteristics including cancer resistance. We show that the healthy longevity characteristics of the Klf1(K74R) mice, as exemplified by their higher anti- cancer capability, are likely gender-, age- and genetic background-independent. Significantly, the anti-cancer capability, in particular that against melanoma as well as hepatocellular carcinoma, and lifespan-extending property of Klf1(K74R) mice could be transferred to wild-type mice via transplantation of their bone marrow mononuclear cells at young age of the latter. Furthermore, NK(K74R) cells carry higher in vitro cancer cell-killing ability than wild type NK cells. Targeted/global gene expression profiling analysis has identified changes of the expression of specific proteins, including the immune checkpoint factors PDCD and CD274, and cellular pathways in the leukocytes of the Klf1(K74R) that are in the directions of anti-cancer and/or anti-aging. This study demonstrates the feasibility of developing a transferable hematopoietic/ blood system for long-term anti-cancer and, potentially, for anti-aging.

cancer biology↗