Spatio-temporal extension in site of origin for cortical calretinin neurons in primates

Abstract

The vast majority of cortical GABAergic neurons can be defined by parvalbumin, somatostatin or calretinin expression. In most mammalians, parvalbumin and somatostatin interneurons have constant proportions, each representing 5–7% of the total neuron number. In contrast, there is a threefold increase in the proportion of calretinin interneurons, which do not exceed 4% in rodents and reach 12% in higher order areas of primate cerebral cortex. In rodents, almost all parvalbumin and somatostatin interneurons originate from the medial part of the subpallial proliferative structure, the ganglionic eminence (GE), while almost all calretinin interneurons originate from its caudal part. The spatial pattern of cortical GABAergic neurons origin from the GE is preserved in the monkey and human brain. However, it could be expected that the evolution is changing developmental rules to enable considerable expansion of calretinin interneuron population. During the early fetal period in primates, cortical GABAergic neurons are almost entirely generated in the subpallium, as in rodents. Already at that time, the primate caudal ganglionic eminence (CGE) shows a relative increase in size and production of calretinin interneurons. During the second trimester of gestation, that is the main neurogenetic stage in primates without clear correlates found in rodents, the pallial production of cortical GABAergic neurons together with the extended persistence of the GE is observed. We propose that the CGE could be the main source of calretinin interneurons for the posterior and lateral cortical regions, but not for the frontal cortex. The associative granular frontal cortex represents around one third of the cortical surface and contains almost half of cortical calretinin interneurons. The majority of calretinin interneurons destined for the frontal cortex could be generated in the pallium, especially in the newly evolved outer subventricular zone that becomes the main pool of cortical progenitors.

Secretagogin is Expressed by Developing Neocortical GABAergic Neurons in Humans but not Mice and Increases Neurite Arbor Size and Complexity

“…These cells often exhibited bipolar or bitufted morphology and coexpressed CR and VIP (Fig. 4E-J), consistent with CGE/LGE origins (Xu et al 2004;Fogarty et al 2007;Miyoshi et al 2010;DeFelipe et al 2013;Ma et al 2013;Dzaja et al 2014;Hladnik et al 2014). …”

“…The increase in the proportion of GABAergic neurons in primate neocortex is thought to primarily reflect an increase in the vasoactive intestinal polypeptide (VIP)/calretinin (CR)-expressing subtype (Hansen et al 2013;Dzaja et al 2014;Hladnik et al 2014;Barinka et al 2015), which arises in the caudal and lateral ganglionic eminences (CGE/LGE) and preferentially occupies superficial cortical layers (Xu et al 2004;Fogarty et al 2007;Miyoshi et al 2010). In humans, half or more of neocortical GABAergic neurons may derive from the CGE (Hansen et al 2013), whereas in mice this number is closer to~30% (Miyoshi et al 2010).…”

The Outer Subventricular Zone and Primate-Specific Cortical Complexification

“…Although the actual proportions of OSVZ generated interneurons-as opposed to subpallium-derived interneurons-is still debated Ma et al, 2013), reports suggest that the OSVZ is the major production site of calretinin neurons (Hladnik et al, 2014), which represent the predominant category of interneurons in primates (12%) as opposed to rodents (4%). Thus, the OSVZ may serve as a permissive niche for the proliferation of GABAergic precursors.…”

New neurons in the adult striatum: from rodents to humans

“…A later study found that a subpopulation of Emx1 -lineage cells originating in the pallium migrates to the developing striatum during early prenatal development [41] and differentiates primarily into DARPP-32-positive medium-sized spiny neurons but also a small number of CR-positive (but no other) striatal interneurons [42]. The pallium has been proposed as the main source of CR+ interneurons in the primate neocortex–and the explanation for the specific expansion of this interneuron subtype in primates [43,44]. It is not yet clear whether any or all adult-born striatal interneurons derive from the Emx-1 lineage in the normal rodent, but these young neurons would represent a small proportion of the interneurons or Emx-1-derived neurons in the rodent striatum and could easily be overlooked.…”

“…Whether generation of striatal interneurons is greater in human than in rodents is less clear. Intriguingly, the proportion of striatal and neocortical interneurons that are CR-positive greatly increases across species, from less than 1% in rodents to 10% in humans, where they represent the predominant interneuron subtype [43,44,61,62]. The size of the vSVZ-derived ICj is also substantially greater in primates than in rodents [17,63].…”