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(2R,6R)-Hydroxynorketamine elicits rapid antidepressant effects by promoting astrocytic μ-δ opioid receptor heterodimerization

Ketamine produces rapid antidepressant effects but is constrained by psychotomimetic properties and abuse potential. The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) shows antidepressant-like efficacy without N-methyl-D-aspartate receptor (NMDAR) blockade, yet its upstream targets remain unclear. Here we show that HNK potentiates hippocampal excitatory transmission and reverses stress-induced behavioural deficits through opioid receptor signaling.

bioRxiv 7d ago

A thalamus–brainstem attractor network drives history-biased decisions

Abstract Natural environments often change gradually, making it adaptive to bias decisions on the basis of the recent past — a phenomenon known as serial dependence1,2,3. Large-scale recordings during behaviour have identified that serial dependence is a common motif for decision-making, with neural representations of past experiences found throughout the brain4,5,6,7,8,9,10,11. However, it remains unclear whether this bias arises from dedicated neural circuits with history-specific...

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