Membrane properties and synaptic regulation of rat globus pallidus neurons.

摘要

The globus pallidus (GP) in rodents, homologous to the external GP of primate not only is considered to be an important integrative locus in basal ganglia, playing a significant role in modulation of information processing within the entire basal ganglia macrocircuit, but also shown to be implicated in the manifestation of parkinsonian motor symptoms. To this end, multidisciplinary studies on understanding the physiology of GP neurons, with particular focus on the membrane properties and synaptic pharmacology of these neurons in vitro, were performed.; Under infrared differential interference contrast (IR-DIC) microscopy, whole cell recordings were made from pallidal slices acutely prepared from young Sprague-Dawley (SD) rats. The predominant group of neurons fired with high frequency with little or no accommodation, in response to depolarizing current injections. On the other hand, these neurons exhibited characteristic slowly developing, time-dependent inward reification when injected with hyperpolarizing current steps, showing the characteristics of the activation of hyperpolarization-activated Ih conductance in these neurons.; On the other hand, the biophysical properties of synaptic GABAA receptor, and the detailed localization and function of GABAB receptors were also studied. Action potential-independent GABAergic synaptic responses, namely miniature postsynaptic currents (mIPSCs) were recorded from pallidal slices. The amplitude distribution of these mIPSCs was highly skewed and exhibited large variability. This variability was found being attributed to multiple afferents synapse on GP neurons.; In addition to metabotropic GABAB receptors expression, the immunohistochemistry for metabotropic glutamate receptors (mGluRs) have also been mapped in GP. GP was found to be one the region that account for highest density of mGluR1alpha in the rat brain. Immunohistochemical experiments using antibodies that raise against mGluR1alpha, demonstrate that these receptors are homogenously expressed in GP and found to localized in the dendrites and sometimes the soma of GP neurons, suggesting they play a very important role in glutamate transmission.; Finally, with the use of s&barbelow;odium d&barbelow;odecyl s&barbelow;ulpfate-digested f&barbelow;reeze-fracture r&barbelow;eplica l&barbelow;abeling (SDS-FRL) technique, we demonstrated that NMDA receptors NR1 and NR2D subunits are targeted to glutamatergic synapses and colocalized with GluR4, a AMPA receptor subunit. Thus these NR2D-containing NMDA receptors are undoubtedly to be activated by spontaneous glutamate release and mediate normal transmission. (Abstract shortened by UMI.)