Striatal ionotropic glutamate receptor ontogeny in the rat.

Rat striatal N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate (KA) receptor staining were evaluated postnatally in the rat. Immunohistochemistry was used to detect subunit proteins of the three glutamate receptor subtypes. The glutamate receptors displayed distinct developmental expression patterns in the striatum. Morphological distributions for the NMDA R1 subunit (representative of NMDA receptors), Glu R1 and Glu R2/3 subunits (indicative of AMPA receptors), and Glu R5/6/7 subunits (demonstrating KA receptors) attained adult expression patterns and levels at different postnatal time points. The ontogenic maturation sequence of striatal glutamate receptor expression was KA, then AMPA and lastly NMDA. Staining patterns for NMDA and AMPA subunit proteins were detected initially as dense patches in the neuropil, which changed to a homogeneous stain of the striatum by the second week of life. Cellular staining for the three subtypes was intense within the highly reactive neuropil patches, but less intensely stained in neurons located outside these zones. The KA receptor subunit did not exhibit neuropil heterogeneity, but was distributed evenly at birth. All three glutamate receptor subtypes were visible within the striatal neuron populations. Populations of striatal neurons that expressed the three differential glutamate receptor subtypes overlap, exhibit different growth patterns and dendritic staining. These results support a functional emergence of different glutamate receptor activation within the striatum and provide a potential therapeutic means to isolate developmental disorders specifically associated with excitatory circuits of the basal ganglia.

Electrophysiological and morphological analyses of cortical neurons obtained from children with catastrophic epilepsy: dopamine receptor modulation of glutamatergic responses.

The present study examined the electrophysiological effects produced by activation of specific dopamine (DA) receptors and the distribution of DA receptor subtypes and glutamate receptor subunits [N-methyl-D-aspartate (NMDAR1) and GluR1] in cortical tissue samples obtained from children (ages 3 months to 16 years) undergoing epilepsy surgery. DA receptor activation produced differential effects depending on the receptor subtype that was activated. D1 receptor family agonists generally enhanced cortical excitability and favored the emergence of epileptogenic activity. In contrast, D2 receptor family agonists had more variable effects on cortical excitability and the expression of epileptiform discharges. Activation of D1 or D2 receptors decreased the amplitude of non-NMDA-mediated excitatory postsynaptic potentials. In contrast, DA and D1 agonists increased the amplitude of NMDA-mediated potentials. Immunohistochemical analysis showed that the DA receptor subtypes and glutamate receptor subunits examined were present in all cortical layers and areas throughout development. Whole-cell voltage clamp recordings of pyramidal neurons visualized with differential interference contrast optics and infrared videomicroscopy indicated that these neurons displayed a persistent Na(+) current, followed by an outward current. DA reduced the outward current but had little effect on the persistent Na(+) current. These results suggest a dual role for DA's actions in the human cerebral cortex. Activation of D2 receptors or antagonism of D1 receptors may help control seizures in children.