Neocortical calretinin neurons in primates: increase in proportion and microcircuitry structure

Abstract

In this article we first point at the expansion of associative cortical areas in primates, as well as at the intrinsic changes in the structure of the cortical column. There is a huge increase in proportion of glutamatergic cortical projecting neurons located in the upper cortical layers (II/III). Inside this group, a novel class of associative neurons becomes recognized for its growing necessity in both inter-areal and intra-areal columnar integration. Equally important to the changes in glutamatergic population, we found that literature data suggest a 50% increase in the proportion of neocortical GABAergic neurons between primates and rodents. This seems to be a result of increase in proportion of calretinin interneurons in layers II/III, population which in associative areas represents 15% of all neurons forming those layers. Evaluating data about functional properties of their connectivity we hypothesize that such an increase in proportion of calretinin interneurons might lead to supra-linear growth in memory capacity of the associative neocortical network. An open question is whether there are some new calretinin interneuron subtypes, which might substantially change micro-circuitry structure of the primate cerebral cortex.

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).…”

“…Neocortical interneurons include spiny nonpyramidal cells, which are mostly excitatory and located in layer IV, and aspiny non-pyramidal cells, which are inhibitory (GABAergic) and distributed throughout the cortical wall (Jones and Peters 1984;DeFelipe et al 2013). Modern estimates indicate that GABAergic neurons comprise~15% of all neocortical neurons in rats and mice and >20% in monkeys and humans (Lin et al 1986;Fitzpatrick et al 1987;Hendry et al 1987;Meinecke and Peters 1987;Beaulieu et al 1992Beaulieu et al , 1994Ren et al 1992;Beaulieu 1993;Hornung and De Tribolet 1994;Jones et al 1994;Micheva and Beaulieu 1995;del Rio and DeFelipe 1996;Gabbott and Bacon 1996;Gabbott et al 1997;Tamamaki et al 2003;Santana et al 2004;Dzaja et al 2014). The proportion is even higher in superficial layers of human neocortex, where nearly 40% of neurons in some regions are GABAergic (del Rio and DeFelipe 1996).…”

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.…”

Mild Traumatic Brain Injury Leads to Decreased Inhibition and a Differential Response of Calretinin Positive Interneurons in the Injured Cortex

“…33 Even though this is a relatively small fraction of the inhibitory neurons, their unique connectivity and placement in the circuitry affords them significant control over inhibitory regulation as a whole. 34 They have been described as being at the top of the intemeuron hierarchy due to the fact that they preferentially regulate the activity of other interneuron populations and specifically target dendritic inhibitory intemeurons to synchronize their activity. 35 • 36 This synchronization of dendritic inhibitory cells is a crucial process to provide effective inhibitory control of excitatory pyramidal cells.…”