Home > Conscious > Chapter 7 > 7.6. Slow Oscillation and HCN Channels


Slow oscillations may occur in slices isolated from a few brain areas. However, in vivo, the slow oscillation always starts from the medial prefrontal cortex layer V, and then propagates to the medial temporal lobe and hippocampus (Massimini et al., 2004). Slow oscillations are local phenomena, some regions can be active while others are silent (Nir et al., 2011). The asynchronization can cause fragmentation of neuronal networks, resulting in unconsciousness (Lewis et al., 2012).

Inhibition of the dopamine's D1 receptor has been shown to increase slow-wave sleep (Monti et al., 1990). Activation of D1 reduces slow-wave sleep (Monti and Monti, 2007). Although dopaminergic neurons are mainly located in ventral tegmental area (VTA) and substantia nigra, the wake-active dopaminergic neurons reside in ventral periaqueductal grey matter (vPAG), which receives GABAergic inputs from ventrolateral preoptic nucleus (VLPO) (Lu et al., 2006). Damages to vPAG result in an increase of slow-wave sleep (Monti and Jantos, 2008). Thus, during natural sleep, the VLPO activated by adenosine may inhibit the dopaminergic neurons in vPAG, attenuating D1 signaling, thereby increasing slow-wave sleep. This mechanism is consistent with the finding that both adenosine increase and VLPO activation can induce slow-wave sleep (Bjorness and Greene, 2009; Varin et al., 2015).

How can D1 inhibition facilitate slow oscillations? Recently, a population of neurons exhibiting slow oscillations have been identified in layer V (5). These neurons are referred to as "network driver cells". Their slow oscillation activities can be facilitated by another group of neurons called "early firing cells". Following application of carbachol (nonselective mAChR agonist), these cells were rapidly and strongly depolarized, leading to continuous firing at the frequency 9.7 ± 2.29 Hz, which is exactly in the α band (Lorincz et al., 2015). These results suggest that the "early firing cells" could contain HCN channels, which are regulated by mAChR and D1 receptor (see Section 7.5). Inhibition of D1 receptor, like activation of mAChR (particularly M2 and M4), should suppress HCN currents and increase the excitability of early firing cells, hence facilitating slow oscillations. This notion is further supported by the finding that the general anesthetics capable of blocking HCN currents also increase slow oscillations (Section 7.8).