An amygdalar oscillator coordinates cellular and behavioral rhythms

Qiang Liu; Jiali Xiong; Dong Won Kim; Sang Soo Lee; Benjamin J Bell; Chloe Alexandre; Seth Blackshaw; Alban Latremoliere; Mark N Wu

doi:10.1016/j.neuron.2024.08.013

An amygdalar oscillator coordinates cellular and behavioral rhythms

Neuron. 2024 Nov 20;112(22):3750-3767.e7. doi: 10.1016/j.neuron.2024.08.013. Epub 2024 Sep 19.

Authors

Qiang Liu¹, Jiali Xiong², Dong Won Kim³, Sang Soo Lee¹, Benjamin J Bell¹, Chloe Alexandre⁴, Seth Blackshaw⁵, Alban Latremoliere⁴, Mark N Wu⁶

Affiliations

¹ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
² Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁴ Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁵ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁶ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: marknwu@jhmi.edu.

PMID: 39303704
PMCID: PMC11581920 (available on 2025-11-20)
DOI: 10.1016/j.neuron.2024.08.013

Abstract

Circadian rhythms are generated by the master pacemaker suprachiasmatic nucleus (SCN) in concert with local clocks throughout the body. Although many brain regions exhibit cycling clock gene expression, the identity of a discrete extra-SCN brain oscillator that produces rhythmic behavior has remained elusive. Here, we show that an extra-SCN oscillator in the lateral amygdala (LA) is defined by expression of the clock-output molecule mWAKE/ANKFN1. mWAKE is enriched in the anterior/dorsal LA (adLA), and, strikingly, selective disruption of clock function or excitatory signaling in adLA^mWAKE neurons abolishes Period2 (PER2) rhythms throughout the LA. mWAKE levels rise at night and promote rhythmic excitability of adLA^mWAKE neurons by upregulating Ca²⁺-activated K⁺ channel activity specifically at night. adLA^mWAKE neurons coordinate rhythmic sensory perception and anxiety in a clock-dependent and WAKE-dependent manner. Together, these data reveal the cellular identity of an extra-SCN brain oscillator and suggest a multi-level hierarchical system organizing molecular and behavioral rhythms.

Keywords: SCN; anxiety; circadian; clock; lateral amygdala; local clock; mWAKE; rhythm; touch.

MeSH terms

Amygdala / metabolism
Amygdala / physiology
Animals
Basolateral Nuclear Complex / metabolism
Basolateral Nuclear Complex / physiology
Behavior, Animal / physiology
Biological Clocks / physiology
Circadian Rhythm* / physiology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neurons* / metabolism
Neurons* / physiology
Period Circadian Proteins* / genetics
Period Circadian Proteins* / metabolism
Suprachiasmatic Nucleus / metabolism
Suprachiasmatic Nucleus / physiology

Substances

Period Circadian Proteins
Per2 protein, mouse

Abstract

MeSH terms

Substances

Grants and funding