1A) have already been described in prior magazines (Hanson et al., 2004;Gnay et al., 2008). constructed some nine GP neuron versions that differed just within their dendritic NaF route appearance level to measure the useful influence of the parameter. The versions were all very similar in their simple electrophysiological features; nevertheless, higher expression degrees of dendritic NaF stations increased the comparative efficiency of distal inputs for both excitatory and inhibitory synapses, broadening the effective level from the dendritic tree. Higher dendritic NaF channel expression also made the neurons more resistant to tonic inhibition and highly sensitive to clustered synchronous excitation. The dendritic NaF channel expression pattern may therefore be a critical determinant of convergence for both the striatopallidal and subthalamopallidal projections, while also dictating which spatiotemporal input patterns are most effective at driving GP neuron output. == Introduction == The globus pallidus (GP in rodents, GPe in primates) is usually a tonically active, inhibitory PF 573228 nucleus in the basal ganglia indirect pathway. GP neurons receive excitation from the subthalamic nucleus (STN) and inhibition from the striatum and from other PF 573228 GP neurons (Falls et al., 1983;Kita and Kitai, 1994;Smith et al., 1998;Sadek et al., 2007). They project to the STN, the basal ganglia output nuclei, and in some cases back to the striatum (Kita and Kitai, 1994;Parent and Hazrati, 1995;Bevan et al., 1998;Smith et al., 1998;Sato et al., 2000). These network connections put the GP in a position to directly influence information flow through the basal ganglia circuit at PF 573228 almost every stage. Rat GP dendritic fields can extend 1 mm in diameter (Park et al., 1982;Millhouse, 1986), nearly one-half the diameter of the whole nucleus, and are positioned with the long axis perpendicular to the topographically organized striatal afferents (Park et al., 1982;Yelnik et al., 1984;Kita and Kitai, 1994). As a result, the distal dendrites on opposite sides of a single GP neuron likely receive synaptic input from nonoverlapping striatal regions, and single striatal axons likely Rabbit Polyclonal to PKA-R2beta contact GP neurons whose cell bodies are far apart (Chang et al., 1981;Park et al., 1982;Wilson and Phelan, 1982;Kawaguchi et al., 1990). The excitatory projection from the STN to GP has a comparable topographical organization (Shink et al., 1996;Smith et al., 1998) and could involve convergence and divergence of connectivity for the same reasons. However, many GP dendrites are of submicron diameter (Difiglia et al., 1982;Park et al., 1982), so passive voltage attenuation will severely reduce the impact of distal synaptic inputs unless counteracted by some form of dendritic amplification. Antibody labeling has demonstrated the presence of fast, transient, voltage-dependent Na+channel (NaF channel) proteins in rat GP dendrites, and whole-cell recordings from brain slices indicated that excitatory synaptic inputs could evoke propagating dendritic spikes in some instances (Hanson et al., 2004). This raises the central question of the present study: in what ways would GP neurons with higher levels of dendritic NaF conductance (gNaF) differ functionally from GP neurons with lower dendriticgNaF? To address this question, we constructed and compared nine model GP neurons that differed only in their dendriticgNaFdistributions. We found that by changing the dendriticgNaFin a declining gradient from the soma to the distal dendritic tips, the totalgNaFexpression level could change by >40-fold while still maintaining realistic spike shapes, rates, and frequency-current response characteristics. Despite their comparable basic profiles, the model neurons differed widely in terms of the spatiotemporal pattern of synaptic input that most effectively drove their activity, indicating an important role of dendritic NaF channels in GP function. == Materials and Methods == == == == == == Electrophysiology. == Coronal slices 300 m in thickness were prepared from 16- to 21-d-old male Sprague Dawley rats according to procedures described previously (Hanson et al., 2004;Gnay et al., 2008). Briefly, rats were anesthetized with halothane and then decapitated. The brains were rapidly removed and immersed in ice-cold artificial CSF (ACSF) made up of the following (in mm): 124 NaCl, 3 KCl, 1.9 MgSO4, 1.2 KH2PO4, 26 NaHCO3, 2 CaCl2, and 20d-glucose, bubbled continuously with a mixture of 95% O2/5% CO2. Each brain was affixed to a chilled stainless steel block with cyanoacrylate glue, the two hemispheres were separated by a midsagittal scalpel cut, and slices were cut with a vibratome (Sigmann Elektronik) and transferred immediately to an incubation chamber made up of.