These peptides elicit “late slow” depolarization that lasts minutes (Jan and Jan, 1982 and Kuffler and Sejnowski, 1983). In addition to suppressing

K+ currents such as the M-current, the neurotransmitters can also excite the neurons through activation of a Na+-dependent basal cation current that is apparently carried by the basal Na+ leak conductance (Brown and Adams, 1980, Jones, 1985 and Kuba and Koketsu, 1978). Such a mechanism of excitation through the activation of Na+-leak-like basal conductances has also been found in the excitation of serotonin neurons in the dorsal raphe nucleus by orexin (Liu et al., 2002), VTA dopaminergic neurons by SP and neurotensin Selleckchem ZVADFMK (Farkas et al., 1996), locus coeruleus neurons by SP and muscarine (Shen and North, 1992a and Shen and North, 1992b), and pre-Bötzinger complex neurons by serotonin

and SP (Peña and Ramirez, 2004 and Ptak et al., 2009). Similarly, suppression of a Na+ leak-like current can lead to hyperpolarization by driving the RMP toward EK, as suggested in the gastrin-releasing peptide containing retinorecipient neurons in the suprachiasmatic nucleus PFI-2 nmr (SCN). In these neurons, a one-hour light exposure causes a large reduction (>100 pA) of what appears to be a Na+-leak current and a hyperpolarization of membrane potential by 15 mV (LeSauter et al., 2011). Background Na+ leak conductances are also implicated in the generation and/or maintenance of spontaneous firing of neurons. Neurons with autonomous firing have been

found in many regions in the nervous systems (Häusser et al., 2004 and Llinás, 1988). The ability to generate rhythmic firing in some neurons is clearly the cell’s intrinsic property as it persists in dissociated neurons in culture and in slices when synaptic transmission is blocked. Subthreshold conductances such as the TTX-sensitive persistent Na+ conductance, resurgent Na+ conductance, voltage-activated Ca2+ channels and Ih have been shown to be the major determinants in the autorhythmicity in many neurons such as cerebellar Purkinje neurons (Raman Carnitine palmitoyltransferase II and Bean, 1997 and Raman et al., 2000) and substantia nigra pars compacta neurons (Chan et al., 2007, Guzman et al., 2009 and Puopolo et al., 2007). In some neurons such as the cerebellar nuclei neurons (Raman et al., 2000), cerebellar unipolar brush cells (Russo et al., 2007), SCN neurons (Jackson et al., 2004), dopaminergic VTA neurons (Khaliq and Bean, 2010), and substantia nigra pars reticulata neurons (Atherton and Bevan, 2005), the autonomous firing also involves conductances similar to the TTX-insensitive background Na+-leak conductance. The presence of such a conductance is proposed to set the “resting” membrane potential close to the threshold (for example −50 mV) above which voltage-sensitive channels are activated, or to depolarize the cells to the threshold potential during inter-spike interval (Khaliq and Bean, 2010).