Slow wave activity in the medial prefrontal cortex of the anaesthetised rat : sub-regional characterisation and dopaminergic modulation

Abstract

During non-rapid eye movement (NREM) sleep, information may be transferred from hippocampus to cortex for long-term storage through synchronised reactivation of these areas. Electrical brain activity during deep NREM sleep consists mainly of a slow (< 1 Hz) alternation between ‘Up’ and ‘Down’ states (UDS). UDS enable the coordination of fast oscillations (> 6 Hz) at different frequencies between different brain regions, which is thought to aid memory consolidation. Coordinated reactivation is though to be guided by the medial prefrontal cortex (mPFC) with its strong connections to many other cortical and subcortical regions. Dopamine strongly modulates mPFC function during wakefulness. However, UDS are not well characterized in the mPFC and little is know about how dopamine modulates mPFC activity during sleep. We recorded UDS in the mPFC of urethane-anaesthetised rats and found significant variation in UDS characteristics both between mPFC sub-regions and between cortical laminae. Activation of the intrinsic dopamine system using tonic, high-frequency electrical stimulation of the ventral tegmental area abolished UDS in the mPFC, shifting activity to a low amplitude fast rhythm, as occurs during rapid eye movement (REM) sleep. This effect was blocked by a dopamine D1 receptor (D1R) antagonist, but not a D2R antagonist. An increase of extracellular dopamine by systemic amphetamine application significantly decreased the power of spindle (6-15 Hz) and gamma (30-80 Hz) oscillations during the Up state. D4R and D1R agonists also affected highfrequency oscillations associated with Up states. These results suggest that D1 receptors might play a role in the change in mPFC activity associated with the transition from NREM sleep to REM sleep. In addition, dopaminergic modulation shows the ability to finely tune Up state-associated fast oscillations, which may potentially be relevant for the coordination between different brain regions, as is necessary for memory consolidation.