Electrical stimulation of the ventral tegmental area evokes sleep‐like state transitions under urethane anaesthesia in the rat medial prefrontal cortex via dopamine D₁‐like receptors

Abstract

The role of dopamine in regulating sleep‐state transitions during, both natural sleep and under anaesthesia, is still unclear. Recording in vivo in the rat mPFC under urethane anaesthesia, we observed predominantly slow wave activity (SWA) of <1 Hz in the local field potential interrupted by occasional spontaneous transitions to a low‐amplitude‐fast (LAF) pattern of activity. During periods of SWA, transitions to LAF activity could be rapidly and consistently evoked by electrical stimulation of the ventral tegmental area (VTA). Spontaneous LAF activity, and that evoked by stimulation of the VTA, consisted of fast oscillations similar to those seen in the rapid eye movement (REM)‐like sleep state. Spontaneous and VTA stimulation‐evoked LAF activity occurred simultaneously along the dorsoventral extent of all mPFC subregions. Evoked LAF activity depended on VTA stimulation current and could be elicited using either regular (25–50 Hz) or burst stimulation patterns and was reproducible upon repeated stimulation. Simultaneous extracellular single‐unit recordings showed that during SWA, presumed pyramidal cells fired phasically and almost exclusively on the Up state, while during both spontaneous and VTA‐evoked LAF activity, they fired tonically. The transition to LAF activity evoked by VTA stimulation depended on dopamine D 1 ‐like receptor activation as it was almost completely blocked by systemic administration of the D 1 ‐like receptor antagonist SCH23390. Overall, our data demonstrate that activation of dopamine D 1 ‐like receptors in the mPFC is important for regulating sleep‐like state transitions.

Amphetamine Promotes Cortical Up State in Part Via Dopamine Receptors

“…In line with our results, D -amphetamine increases the release of both NE and DA ( Kuczenski and Segal, 1997 ; Rothman et al, 2001 ) and has been shown to accelerate emergence from anesthesia via DA receptors ( Taylor et al, 2013 ; Kenny et al, 2015 ). Furthermore, activation of DA neurons in the ventral tegmental area is known to induce an Up state-like depolarization in PFC pyramidal neurons ( Lewis and O’donnell, 2000 ; Onn and Wang, 2005 ; Iwashita, 2014 ; Gretenkord et al, 2020 ), accelerate emergence from anesthesia ( Solt et al, 2014 ; Taylor et al, 2016 ), and promote wakefulness ( Eban-Rothschild et al, 2016 ; Oishi et al, 2017a ; Sun et al, 2017 ). Additional evidence suggests that DA produces these effects, at least in part, via D1 and D2-like receptors in the nucleus accumbens ( Eban-Rothschild et al, 2016 ; Oishi et al, 2017b ; Luo et al, 2018 ; Zhang et al, 2021 ).…”

The role of intracerebral dopamine D1 and D2 receptors in sleep‐wake cycles and general anesthesia

“…What's more, electrical stimulation of VTA continuously eliminates slow‐wave activity (SWA) and induces low amplitude rapid (LAF) network rhythm, similar to REMs. Systemic infusion of D1‐like receptors antagonist inhibited the effects of VTA stimulation in all mPFC subregions, implying that DA mediates the shift from SWA to REM‐like state induced by VTA stimulation through D1‐like receptors 36 …”

“…Systemic infusion of D1-like receptors antagonist inhibited the effects of VTA stimulation in all mPFC subregions, implying that DA mediates the shift from SWA to REM-like state induced by VTA stimulation through D1-like receptors. 36 In another study, microinjecting D1R agonist or antagonist facilitated or delayed the awakening from isoflurane anesthesia in young mice by activating or inhibiting D1Rs in the NAc shell, respectively. Nonetheless, this modulation capacity of D1Rs in the NAc shell declined in aged mice.…”

“…Previous studies have indicated that electrical stimulation of VTA, the major dopaminergic nuclei, resulted in membrane depolarization of putative pyramidal cells in the rat's mPFCunder urethane anesthesia 36 . What's more, electrical stimulation of VTA continuously eliminates slow‐wave activity (SWA) and induces low amplitude rapid (LAF) network rhythm, similar to REMs.…”

Investigação da modulação dopaminérgica na sincronia da atividade oscilatória da circuitaria hipocampo-córtex pré-frontal

“…Nosso grupo (Ruggiero et al, 2018; (Morales & Margolis, 2017). A transição é marcada pela alteração na dinâmica oscilatória do PFC regulada por receptores dopaminérgicos D 1 , e é observada também durante sono natural (Gretenkord et al, 2019). Também foi mostrado que a depleção aguda de dopamina suprime parcialmente o sono de ondas lentas e totalmente o sono REM, sendo este último recuperado pela injeção sistêmica de agonistas de receptores dopaminérgicos D 2 , mas não D 1 .…”