The modification of the discharge pattern of subthalamic nucleus (STN) neurons from single-spike activity to mixed burstfiring mode is one of the characteristics of parkinsonism in rat and primates. However, the mechanism of this process is not yet understood. Intrinsic firing patterns of STN neurons were examined in rat brain slices with intracellular and patch-clamp techniques. Almost half of the STN neurons that spontaneously discharged in the single-spike mode had the intrinsic property of

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... witching to pure or mixed burst-firing mode when the membrane was hyperpolarized from Ϫ41.3 Ϯ 1.0 mV (range, Ϫ35 to Ϫ50 mV; n ϭ 15) to Ϫ51.0 Ϯ 1.0 mV (range, Ϫ42 to Ϫ60 mV; n ϭ 20). This switch was greatly facilitated by activation of metabotropic glutamate receptors with 1S,3R-ACPD. Recurrent membrane oscillations underlying burst-firing mode were endogenous and Ca 2ϩ -dependent because they were largely reduced by nifedipine (3 M), Ni 2ϩ (40 M), and BAPTA-AM (10-50 M) at any potential tested, whereas TTX (1 M) had no effect. In contrast, simultaneous application of TEA (1 mM) and apamin (0.2 M) prolonged burst duration. Moreover, in response to intracellular stimulation at hyperpolarized potentials, a plateau potential with a voltage and ionic basis similar to those of spontaneous bursts was recorded in 82% of the tested STN neurons, all of which displayed a low-threshold Ni 2ϩsensitive spike. We propose that recurrent membrane oscillations during bursts result from the sequential activation of T/Rand L-type Ca 2ϩ currents, a Ca 2ϩ -activated inward current, and Ca 2ϩ -activated K ϩ currents. Key words: tonic and bursting activities of STN neurons in slices; burst ionic mechanisms; low-threshold spike; Ca 2ϩdependent plateau potential; intracellular and patch-clamp recordings; Parkinson's disease The subthalamic nucleus (STN) is composed of glutamatergic neurons that control the circuitry of the basal ganglia by modulating the activity of the two principal output structures of the network: the internal pallidal segment and the substantia nigra pars reticulata (for review, see Albin et al.