Background: Ventral tegmental area (VTA) glutamatergic neurons promote wakefulness in the sleep-wake cycle; however, their roles and neural circuit mechanisms during isoflurane (ISO) anesthesia remain unclear.
Methods: Fiber photometry and in vivo electrophysiology were used to observe the changes in neuronal or terminal activity during ISO anesthesia and arousal processes. Optogenetic and anesthesia behaviors were used to investigate the effects of VTA glutamatergic neurons and their projections to the lateral septum (LS) during ISO anesthesia and arousal. Anterograde and retrograde tracings were performed to identify the connections between VTA glutamatergic neurons and the LS.
Results: Population activity and firing rates of VTA glutamatergic neurons decreased during ISO anesthesia (ISO: 95% confidence interval [CI], 0.83-2.06 Spikes.s -1 vs wake: 95% CI, 3.53-7.83 Spikes.s -1 ; P =.0001; n = 34 from 4 mice). Optogenetic activation of VTA glutamatergic neurons reduced the burst-suppression ratio in electroencephalography (laser: 95% CI, 13.09%-28.76% vs pre: 95% CI, 52.85%-71.59%; P =.0009; n = 6) and facilitated emergence (ChR2: 95% CI, 343.3-388.0 seconds vs mCherry: 95% CI, 447.6-509.8 seconds; P < .0001; n = 11/12) from ISO anesthesia. VTA glutamatergic neurons monosynaptically innervated LS γ-aminobutyric acid (GABA)-ergic neurons. The activity of VTA glutamatergic terminals in the LS decreased during ISO anesthesia, and optogenetic activation of the VTA glutamatergic terminals in the LS facilitated emergence from ISO anesthesia. Furthermore, optogenetic activation of VTA glutamatergic terminals increased the firing rates of LS γ-aminobutyric acid-ergic (GABAergic) neurons (laser: 95% CI, 0.85-4.03 Spikes.s -1 vs pre: 95% CI, 0.24-0.78 Spikes.s -1 ; P =.008; n = 23 from 4 mice) during ISO anesthesia.
Conclusions: VTA glutamatergic neurons facilitated emergence from ISO anesthesia involving excitation of LS GABAergic neurons.
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http://dx.doi.org/10.1213/ANE.0000000000006739 | DOI Listing |
bioRxiv
December 2024
Department of Anesthesiology, Center for Clinical Pharmacology, Washington University Pain Center, Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Distinct excitatory synaptic inputs to the locus coeruleus (LC) modulate behavioral flexibility. Here we identify a novel monosynaptic glutamatergic input to the LC from the ventral tegmental area (VTA). We show robust VTA axonal projections provide direct glutamatergic transmission to LC.
View Article and Find Full Text PDFCNS Neurosci Ther
November 2024
Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Background: Dorsal raphe nucleus (DRN) serotonergic neurons projecting to the ventral tegmental area (VTA) neural circuit participate in regulating wake-related behaviors; however, the effect and mechanism of which in regulating sleep-wake are poorly understood.
Methods: Fiber photometry was used to study DRN serotonergic afferent activity changes in the VTA during sleep-wake processes. Optogenetics and chemogenetics were took advantage to study the effects of DRN serotonergic afferents modulating VTA during sleep-wake.
Eur J Pharmacol
January 2025
Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, 430048, China; Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, China.
The ventral tegmental area (VTA), located in the midbrain, plays a pivotal role in the regulation of many important behaviors, such as reward, addiction, aversion, memory, learning, and sleep-wakefulness cycles. The majority of VTA neurons are dopaminergic neurons, although there is a significant proportion of GABAergic neurons and few glutamatergic neurons. These neuronal types project to different brain regions, thus mediating various biological functions.
View Article and Find Full Text PDFBrain Res
February 2025
Physiology Research Group, Stress, Memory and Behavior Lab, Federal University of Pampa, Uruguaiana, RS, Brazil. Electronic address:
Br J Pharmacol
January 2025
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Background And Purpose: GABAergic neurons in mouse ventral tegmental area (VTA) exhibit elevated activity during withdrawal following chronic ethanol exposure. While increased glutamatergic input and decreased GABA receptor sensitivity have been implicated, the impact of inhibitory signaling in VTA GABA neurons has not been fully addressed.
Experimental Approach: We used electrophysiological and ultrastructural approaches to assess the impact of chronic intermittent ethanol vapour exposure in mice on GABAergic transmission in VTA GABA neurons during withdrawal.
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