Expression of GABA and GABA_a receptors by neurons of the subplate zone in developing primate occipital cortex: Evidence for transient local circuits

Abstract

Several lines of evidence suggest that the transient subplate zone of the embryonic mammalian telencephalon could influence cortical development through synaptic or trophic interactions with growing cortical afferents and migrating neurons. Since such interactions may involve neurotransmitters and their receptor molecules, we have examined the expression of GABA and subunits of the GABAA/benzodiazepine receptor complex in the occipital lobe of embryonic rhesus monkeys by immunochemistry and in situ hybridization. We found that during the second half of gestation, when the subplate zone reaches peak maturity in this species, many neurons can be immunolabeled with both GABA antisera and monoclonal antibodies against GABAA receptor subunits. The most robust labeling occurs at approximately embryonic day (E)125 (birth is at E165). Electron microscopic observations of receptor subunit-immunolabeled material confirmed that subunits of the GABAA receptor are localized in the subplate neurons and their dendritic processes. In many instances the reaction product is associated with the plasma membranes of labeled processes, some of which form symmetrical synapses with small unlabeled axon terminals. The results of in situ hybridization are in accord with the results of receptor subunit immunochemistry. From E80 to E141, hybridization signal for GABAA receptor subunit mRNA occurs in the subplate zone and increases steadily to peak levels between E125 and E141. The present results reveal that all the elements necessary for the formation of functional GABAergic synaptic circuitry are present in the subplate zone. Further, the ages showing the most pronounced receptor and transmitter expression in this primate coincide with the ingrowth of major cortical afferent systems. Taken together, these findings suggest that GABAergic local neuronal circuits in the subplate may be involved in the development of long tract connections stationed in this zone prior to their transfer to the overlying cortical plate.

Development of axonal pathways in the human fetal fronto‐limbic brain: histochemical characterization and diffusion tensor imaging

“…This concept is further supported by the shifts in molecular markers (Bayatti et al 2008a,b). The molecular identification of subplate neurons was the research goal for multiple groups (Chun & Shatz, 1988;Meinecke & Rakic, 1992;Delalle et al 1997;Kwan et al 2008;Ayoub & Kostović, 2009;Hoerder-Suabedissen et al 2009;McKellar & Shatz, 2009;Osheroff & Hatten, 2009). Zečević and colleagues have shown that glial cells also show differential distribution within the subplate (Jakovcevski & Zecevic, 2005).…”

Subplate in the developing cortex of mouse and human

“…Both electrophysiological properties and cell morphology point to a high degree of underlying diversity among subplate neurons (Antonini & Shatz, 1990;Hanganu et al 2001;Hoerder, 2007). There are two basic classes of neuronal phenotypes in the subplate, glutamatergic and c-aminobutyric acid (GABA)ergic (Antonini & Shatz, 1990;Meinecke & Rakic, 1992), with each class expressing heterogeneous molecular markers (Allendoerfer & Shatz, 1994;Hevner & Zecevic, 2006;Hoerder-Suabedissen et al 2009). It is not yet clear whether the same types of subplate neurons possess intracortical and extracortical projections and how the diverse somatodendritic morphologies relate to the equally diverse neurochemical properties and physiological fingerprints.…”

Early history of subplate and interstitial neurons: from Theodor Meynert (1867) to the discovery of the subplate zone (1974)

“…On the other hand, in humans and monkeys a substantial portion of both subplate and interstitial neurons are probably GABAergic inhibitory interneurons (Kostović & Rakic, 1990;Meinecke & Rakic, 1992; for review see Judaš et al, 2010). Therefore, we recently proposed ) that GABAergic interstitial neurons serve as important modulators of normal cortical functions and that this inhibitory action is facilitated by their strategic position at the cortical ⁄ white matter interface where limbic and modulatory afferent pathways enter the prefrontal cortex.…”