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RESEARCH PRODUCT

Subthreshold oscillation of the membrane potential in magnocellular neurones of the rat supraoptic nucleus

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The hypothalamic supraoptic nucleus (SON) contains two major populations of magnocellular neurosecretory neurones, producing and secreting vasopressin and oxytocin, respectively (for review see Poulain & Wakerley 1982). Neurones of a subpopulation of supraoptic neurosecretory cells share the capability of generating phasic bursts of action potentials. In these neurones, action potentials are succeeded by a depolarizing afterpotential (DAP; Andrew, 1987; Armstrong et al. 1994; Li et al. 1995). Depending on the discharge frequency, DAPs summate, eventually resulting in the generation of a plateau potential that gives rise to the discharge of a long-lasting train of action potentials. Thus, DAPs may provide a mechanism for the maintenance of the active state. The initiation of rhythmic bursting, i.e. the repetitive slow transition between active and inactive states, was assumed to depend on the occurrence of slow depolarizations (Andrew, 1987). The duration of phasic burst discharge in rat supraoptic neurones in vitro was reported to range from 1 s to 5 min (Inenaga et al. 1993). In SON neurones displaying both phasic discharge and DAPs, intrinsic oscillatory burst activity was reported to occur during perifusion of brain slices with low-calcium perifusion medium (Li & Hatton, 1996). These bursts were observed to repeat with a mean interval of 453 ms. Damped rhythmic oscillation of the membrane potential with an initial duration of 140 to 300 ms were reported to occur in magnocellular neurones of the guinea-pig SON (Erickson et al. 1993). On a shorter time scale, repetitively occurring non-synaptic depolarizing potentials (NSDPs) of 20 to 125 ms duration were observed to be generated 5-7 mV subthreshold to the initiation of spike discharge in rat supraoptic neurones (Bourque et al. 1986). NSDPs were suggested to be involved in spike and burst triggering. Similar functional roles for the regulation of neuronal activity in other brain regions were attributed to higher frequency subthreshold oscillatory activity (Alonso & Klink, 1993; Lampl & Yarom, 1993). The occurrence of endogenous subthreshold oscillatory activity was demonstrated in a variety of neuronal systems including the neocortex (Gray et al. 1989; Gutfreund et al. 1995), the entorhinal cortex (Alonso & Klink, 1993), the thalamus (McCormick & Pape, 1990), the nucleus basalis magnocellularis (Alonso et al. 1996), the amygdaloid complex (Pareet al. 1995; Pape et al. 1998; Pape & Driesang, 1998), the inferior olive (Llinas & Yarom, 1986; Bal & McCormick, 1997) and the dorsal root ganglia (Amir et al. 1999). Ionic mechanisms involved in rhythmogenesis of repetitive fluctuations of the membrane potential seem to be as manifold as the characteristics of oscillatory phenomena. The generation of slow oscillatory activity in SON neurones seems to depend on the rhythmic increase and decrease of calcium influx (Andrew, 1987) or depends on calcium currents and TTX-sensitive sodium currents (Inenaga et al. 1993). Rapid mobilization of calcium from intracellular stores, influx of sodium through persistent sodium channels (INa,P) as well as gap junctions were reported to be important for the generation of slow oscillatory activity in supraoptic neurones of the rat observed during perifusion with low calcium medium (Li & Hatton, 1996). In SON neurones of the guinea-pig, a T-type calcium current (IT) and mechanisms generating depolarizing afterpotentials were associated with damped membrane potential oscillations (Erickson et al. 1993). Concerning the generation of fast oscillatory activity, the interplay between IT and a hyperpolarization-activated cation current (Ih) was shown to be important in the lateral geniculate nucleus (McCormick & Pape, 1990) as well as in the inferior olive (Bal & McCormick, 1997). In other neuronal systems TTX-sensitive conductances seem to be of high importance for the generation of subthreshold oscillation of the membrane potential. Oscillations in stellate cells of the entorhinal cortex are generated by the interplay of INa,P and an outward rectifying potassium conductance blocked by barium (Klink & Alonso, 1993). Fast oscillations in cortical pyramidal cells were blocked by TTX or a high concentration of tetraethylammonium (TEA; Gutfreund et al. 1995) and were simulated in a model to be generated by the interaction of INa,P and a slow non-inactivating potassium current. In the basolateral amygdala, subthreshold oscillations were blocked by TTX or carbachol (Pape & Driesang, 1998) suggesting the contribution of INa,P and the M-type potassium current (IM) to the rhythmogenesis. Additionally, oscillatory activity in dorsal root ganglion neurones was demonstrated to be sensitive to the application of the local anaesthetic lidocaine (Amir et al. 1999). In the present study, we report the occurrence, properties and ionic basis of rhythmic subthreshold oscillation of the membrane potential in magnocellular neurones of the rat SON in a brain slice preparation. The initiation of subthreshold oscillation is voltage dependent and is eliminated by TTX, procaine or 15 mM TEA, but is not blocked during superfusion with low Ca2+-high Mg2+ artificial cerebrospinal fluid (ACSF) or by Cd2+. The latter is also true for various potassium channel antagonists and the IM channel agonist carbachol. Furthermore, subthreshold oscillation can still be induced during the application of the uncoupling agent heptanol. Part of this work has been presented in abstract form (Greffrath et al. 1999).