Neurons that fire spontaneously set a rhythm of tonic activity in many brain areas. Ethanol alters activity of distinct types of these “tonically active” neurons. Although ethanol potentiates the firing of dopamine neurons, it inhibits the firing of midbrain GABAergic neurons (Adermark et al., 2014; Burkhardt and Adermark, 2014; Stobbs et al., 2004) (Figure 2G). Interneurons of the striatum are also differentially affected by acute ethanol (Blomeley et al., 2011; Clarke and Adermark, 2015). Ethanol decreases the tonic firing frequency of cholinergic interneurons in the striatum, which then affects the activity of medium spiny neurons (MSNs) (Adermark et al., 2011b; Blomeley et al., 2011) (Figure 2H). These findings indicate that ethanol’s effects on intrinsic excitability are region and cell-type specific. Indeed, in the globus pallidus external segment, acute ethanol decreases the firing of low-frequency, but not high-frequency, firing neurons. The ethanol-induced inhibition of low-frequency firing neurons is attributable to ethanol activation of the BK channel (Abrahao et al., 2017). Thus, this is one neuronal subtype in which the bottom-up approach can be used to assess the circuit and behavioral effects of BK activation by ethanol.
