PSEM agonist for chimeric ligand-gated ion channel pores with nAChR α7 LBD L141F or L141F/Y115F mutant (PSAM) in vitro and in vivo.
PSEM89S is a pharmacologically selective effector molecule (PSEM) that acts as a selective agonist in vitro and in vivo for chimeric pharmacologically selective actuator modules (PSAMs) composed of nAChR α7 ligand-binding domain (LBD) with L141F mutation fused to the ion pore domain (IPD) of a ligand-gated ion channel (LGIC), including glycine receptor (PSAML141F-GlyR & PSAML141F/Y115F-GlyR). 5-HT3 (PSAML141F-5-HT3 & PSAML141F/Y115F-5-HT3) and high-conductance 5-HT3 (PSAML141F-5-HT3 HC & PSAML141F/Y115F-5-HT3 HC).
Direction-selective ganglion cells (DSGCs) are tuned to motion in one direction. Starburst amacrine cells (SACs) are thought to mediate this direction selectivity through precise anatomical wiring to DSGCs. Nevertheless, we previously found that visual adaptation can reverse DSGCs's directional tuning
Opioids are widely used medicinally as analgesics and abused for hedonic effects, actions that are each complicated by substantial risks such as cardiorespiratory depression. These drugs mimic peptides such as β-endorphin, which has a key role in endogenous analgesia. The
Homeostasis is a biological principle for regulation of essential physiological parameters within a set range. Behavioural responses due to deviation from homeostasis are critical for survival, but motivational processes engaged by physiological need states are incompletely understood. We examined motivational
The locus coeruleus (LC) projects throughout the brain and spinal cord and is the major source of central noradrenaline. It remains unclear whether the LC acts functionally as a single global effector or as discrete modules. Specifically, while spinal-projections from
We examined adaptations in nucleus accumbens (NAc) neurons in mouse and rat peripheral nerve injury models of neuropathic pain. Injury selectively increased excitability of NAc shell indirect pathway spiny projection neurons (iSPNs) and altered their synaptic connectivity. Moreover, injury-induced tactile
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