Regulation of limbic information outflow by the subthalamic nucleus: Excitatory amino acid projections to the ventral pallidum

The subthalamic nucleus (STN), a component of the basal ganglia motor syste m, sends an excitatory amino acid (EAA)containing projection to the ventral pallidum (VP), a major limbic system output region. The VP contains both N MDA and AMPA subtypes of EAA receptors. To characterize the physiology of t he subthalamic pathway to the VP, and to determine the influence of EAA rec eptor subtypes, in vivo intracellular recordings, and in vivo extracellular recordings combined with microiontophoresis, were made from VP neurons in anesthetized rats. Of the intracellularly recorded neurons, 86% responded t o STN stimulation, and these, displayed EPSPs with an onset of 8.7 msec, co nsistent with a monosynaptic input. The EPSPs evoked in spontaneously firin g neurons were nearly twice the amplitude of those in nonfiring cells (13.1 vs 6.8 mV, respectively). As neurons were depolarized by current injection , the latency for spiking decreased from 24.2 to 14.2 msec, although EPSP l atency was unaffected. Eighty-seven percent of the extracellularly recorded VP neurons responded to STN stimulation with a rapid and robust enhancemen t of spiking; the response onset, like the EPSP onset, equaled 8.7 msec. Fi ring rate was enhanced by NMDA in 94% of the STN-excited cells, and AMPA in creased firing in 94% as well. The NMDA-selective antagonist AP-5 attenuate d 67% of the STN-evoked excitatory responses, and the AMPA-selective antago nist CNQX attenuated 52%. Both antagonists attenuated 33% of responses, and 78% were attenuated by at least one. This evidence suggests that a great m ajority of VP neurons are directly influenced by STN activation and that bo th NMDA and non-NMDA receptors are involved. Moreover, the VP response to S TN stimulation appears to be strongly dependent on the depolarization state of the neuron.