Quantitative localization of AMPA/kainate and kainate glutamate receptor subunit immunoreactivity in neurochemically identified subpopulations of neurons in the prefrontal cortex of the macaque monkey

Abstract

Excitatory amino acid transmission has been proposed as the principal synaptic mechanism for distribution of information through corticocortical and thalamocortical pathways. The following study utilized a double labeling paradigm, using antibodies that recognize non-NMDA ionotropic glutamate receptor subunits and other neuronal markers, to further define, quantitatively, the subclasses of neurons that contain immunoreactivity for the AMPA/kainate and kainate receptor subunits in the monkey prefrontal cortex. Double labeling with an antibody that recognizes common epitopes in AMPA/kainate subunits GluR2 and GluR3 (GluR2/3) in combination with an antibody that recognizes the kainate receptor subunits GluR5, GluR6, and GluR7 (GluR5/6/7) demonstrated that immunoreactivity for these two receptor classes was highly colocalized in a great majority of the pyramidal neurons in this region but present in only a minority of neurochemically identified subclasses of GABAergic interneurons. Furthermore, GluR2/3 immunoreactivity had principally a somatic distribution whereas GluR5/6/7 labeling was predominately found in the perikarya and/or particular dendritic domains. In contrast, intense GluR1 labeling was observed in a small subpopulation of interneurons and low GluR1 immunoreactivity was present in many other cortical neurons. These results demonstrate that there is a high degree of specificity in the distribution of AMPA/kainate and kainate receptor-class proteins to subclasses of neurons within the neocortex. A neuron's combination of excitatory amino acid receptor subunits may regulate its response to excitatory inputs and further defines the role of identified subclasses of neurons in the complex circuitry of the cerebral cortex and may also indicate the basis for the apparent cellular selectivity of excitotoxic degenerative processes.

Kainate receptor gene expression in the developing rat brain

“…Growth rates of developing dendrites can be slowed down by focal application of physiological concentrations of glutamate or kainate to individual growth cones (Mattson et al, 1988a). These regressive effects of kainate are mediated by ionotropic receptors located on the growth cone (Mattson et al, 1988a,b) and would be in keeping with dendritic locations seen in the adult Vickers et al, 1993). In a study using cultured cerebellar granule cells, kainate (60 PM) enhanced neurite development (both elongation and sprouting), whereas AMPA (20 /IM) had no effect (Pizzi et al, 1994).…”

“…This observation might further support the idea of kainate-selective receptors that are present on dendrites or axons. Immunocytochemistry with an antibody that cross-reacts with the GluR-5, GluR-6, and GluR-7 subunits shows that these subunits are particularly enriched on dendritic shafts Vickers et al, 1993) although this has not been so far examined in the developing CNS.…”

A neurochemical signature of visual recovery after extrastriate cortical damage in the adult cat

“…Previous reports in rodents (Geiger et al, 1995;Vissavajjhala et al, 1996;Angulo et al, 1997;Kondo et al, 1997) and primates (Vickers et al, 1993;Munoz et al, 1999) suggest that some classes of cortical neurons, including those expressing calcium-binding proteins, can be differentiated by their expression of different AMPA receptor subunits. However, our present experiments revealed that in normal cats, the great majority of calbindin-and parvalbuminpositive cells, and the majority of LS-projecting pyramidal cells in layer II/III of area 18 expressed all four subunits of the AMPA receptor.…”

“…They are comprised of four subunits-GluR1, GluR2, GluR3, and GluR4-that are differentially expressed in different neurons (Vickers et al, 1993;Geiger et al, 1995; Vissavaijhala et al, 1996;Angulo et al, 1997;Kondo et al, 1997;Munoz et al, 1999;Van Damme et al, 2003). Although many glutamate receptors (such as AMPA, N-methyl-D-aspartate [NMDA], kainate) play a role in activity-dependent neuronal plasticity (Collingridge and Singer, 1990;Malenka and Nicoll, 1993), the sensitivity of AMPA receptor to changes in connectivity and function within the cat visual system has been well demonstrated (Gordon et al, 1996;Price and Huxlin, 2001;Van Damme et al, 2003).…”

Immunolocalization of NMDA receptors in the central nervous system of weakly electric fish: functional implications for the modulation of a neuronal oscillator

“…Recently, antibodies raised against subunits of other amino acid receptors have served as useful tools to explore receptor location on large populations of cells with cellular and often subcellular resolution (Rogers et al, 1991;Blackstone et al, 1992a,b;Hampson et al, 1992;Martin et al, 1992;Petralia and Wenthold, 1992;Huntley et al, 1993;Martin et al, 1993a,b;Vickers et al, 1993). The immunohistochemical approach complements and offers some advantages over previous efforts at receptor localization using microelectrodes and pharmacological manipulations, as well as labeled-ligand binding and in situ hybridization techniques.…”