Inhibitory interneurons regulate phasic activity of noradrenergic neurons in the mouse locus coeruleus and functional implications

doi:10.1113/JP279557

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24492

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24492

Title:	Inhibitory interneurons regulate phasic activity of noradrenergic neurons in the mouse locus coeruleus and functional implications
Authors:	Kuo, CC;Hsieh, JC;Tsai, HC;Kuo, YS;Yau, HJ;Chen, CC;Chen, RF;Yang, HW;Min, MY
Keywords:	chemogenetic;optogenetic;orbitofrontal cortex;prelimbic cortex;prepulse inhibition;whole-cell patch
Date:	2020
Issue Date:	2022-08-09T08:03:13Z (UTC)
Publisher:	WILEY
ISSN:	0022-3751
Abstract:	Key points The locus coeruleus (LC) contains noradrenergic (NA) neurons that respond to novel stimuli in the environment with phasic activation to initiate an orienting response; phasic LC activation is also triggered by stimuli, representing the outcome of task-related decision processes, to facilitate ensuing behaviours and help optimize task performance. Here, we report that LC-NA neurons exhibit bursts of action potentialsin vitroresembling phasic LC activationin vivo, and the activity is gated by inhibitory interneurons (I-INs) located in the peri-LC. We also observe that inhibition of peri-LC I-INs enhances prepulse inhibition and axons from cortical areas that play important roles in evaluating the cost/reward of a stimulus synapse on both peri-LC I-INs and LC-NA neurons. The results help us understand the cellular mechanisms underlying the generation and regulation of phasic LC activation with a focus on the role of peri-LC I-INs. Noradrenergic (NA) neurons in the locus coeruleus (LC) have global axonal projection to the brain. These neurons discharge action potentials phasically in response to either novel stimuli in the environment to initiate an orienting behaviour or stimuli representing the outcome of task-related decision processes to facilitate ensuing behaviours and help optimize task performance. Nevertheless, the cellular mechanisms underlying the generation and regulation of phasic LC activation remain unknown. We report here that LC-NA neurons recorded in brain slices exhibit bursts of action potentials that resembled the phasic activation-pause profile observed in animals. The activity was referred to as phasic-like activity (PLA) and was suppressed and enhanced by blocking excitatory and inhibitory synaptic transmissions, respectively. These results suggest the existence of a local circuit to drive PLA, and the activity could be regulated by the excitatory-inhibitory balance of the circuit. In support of this notion, we located a population of inhibitory interneurons (I-INs) in the medial part of the peri-LC that exerted feedforward inhibition of LC-NA neurons through GABAergic and glycinergic transmissions. Selective inhibition of peri-LC I-INs with chemogenetic methods could enhance PLA in brain slices and increase prepulse inhibition in animals. Moreover, axons from the orbitofrontal and prelimbic cortices, which play important roles in evaluating the cost/reward of a stimulus, synapse on both peri-LC I-INs and LC-NA neurons. These observations demonstrate functional roles of peri-LC I-INs in integrating inputs of the frontal cortex onto LC-NA neurons and gating the phasic LC output.
URI:	http://dx.doi.org/10.1113/JP279557 https://www.webofscience.com/wos/woscc/full-record/WOS:000550517000001 https://ir.csmu.edu.tw:8080/handle/310902500/24492
Relation:	JOURNAL OF PHYSIOLOGY-LONDON ,2020 ,v598 ,issue 18 ,p4003-4029
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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