Cell-type homologies and the origins of the neocortex

Abstract

The six-layered neocortex is a uniquely mammalian structure with evolutionary origins that remain in dispute. One long-standing hypothesis, based on similarities in neuronal connectivity, proposes that homologs of the layer 4 input and layer 5 output neurons of neocortex are present in the avian forebrain, where they contribute to specific nuclei rather than to layers. We devised a molecular test of this hypothesis based on layer-specific gene expression that is shared across rodent and carnivore neocortex. Our findings establish that the layer 4 input and the layer 5 output cell types are conserved across the amniotes, but are organized into very different architectures, forming nuclei in birds, cortical areas in reptiles, and cortical layers in mammals.T he evolutionary origins of the mammalian neocortex have been the subject of debate for over a century (1-3). Although the six-layered neocortex is remarkably well conserved in all extant mammals, it is not present in our closest living relatives, the reptiles and birds. Birds in particular are an extremely successful radiation with large brains, but the bird dorsal telencephalon does not include a morphologically identifiable cortex; it is, instead, a collection of nuclei (4).Studies of the neurochemistry, anatomy, and physiology of the central region of the bird telencephalon, which is called the dorsal ventricular ridge (DVR), have shown conclusively that the DVR is a pallial structure (2). In mammals the pallium (dorsal telencephalon) includes the neocortex and the nuclei of the piriform lobe, specifically the claustrum and parts of the amygdala. A classical hypothesis that has attracted renewed interest from modern neuroembryologists and neuromorphologists proposes a field homology between the nuclei of the bird DVR and the mammalian piriform lobe nuclei, including the amygdala (5, 6). A second, more controversial hypothesis proposes that, despite the gross differences in morphology between bird DVR and mammalian neocortex, these structures share a homology (7-9).The best evidence for neocortex-DVR homology lies in their circuitries. Both the mammalian neocortex and avian DVR receive ascending sensory input from the thalamus, and both send outputs to brainstem premotor areas. These input and output territories form specific, well-defined populations of neurons in both mammals and birds. In mammals, layer 4 neocortical neurons receive thalamic input, and layer 5 neocortical neurons project to the brainstem. In birds there are separate DVR nuclei that receive projections from the thalamus or send axons to the brainstem. The most developed version of the neocortex-DVR hypothesis proposes homology between these input and output neurons at the cell-type level (7); specifically, that the layer 4 input (L4/I) and layer 5 output (L5/O) neurons of the neocortex share a common ancestry with neurons that populate the input and output nuclei of the DVR.These two prevailing hypotheses about DVR homology are in direct conflict; one is a field homology argument comparing...

Task-related “cortical” bursting depends critically on basal ganglia input and is linked to vocal plasticity

“…Moreover, as with the prefrontal cortex, stimulation of LMAN does not evoke motor (song) output (24,46,63). Alternatively, or in addition, with respect to the hypothesis that avian nuclei are homologous to mammalian cortical layers (11,12,64), LMAN shares some but not all of the features of layer II/III intracortically connecting neurons. Yellow, green, and purple boxes indicate basal ganglia, thalamic, and cortical structures, respectively.…”

“…The AFP indirectly connects the song premotor cortical analog HVC (HVC is used as its proper name) and the song motor cortical analog RA (robust nucleus of the arcopallium) via the basal ganglia (striato-pallidal) nucleus Area X, the thalamus, and the prefrontal cortical analog LMAN (lateral magnocellular nucleus of the nidopallium) [see Fig. 1A for specific parallels to mammals; although these parallels are not complete (11,12), for simplicity we hereafter refer to LMAN as cortical]. As in mammals, the AFP is not required for the production of well-learned behaviors, but it is critically important for motor plasticity (13)(14)(15)(16)(17)(18).…”

From sauropsids to mammals and back: New approaches to comparative cortical development

“…However, regions such as the striatum and hippocampus, which share homology and function between birds and mammals, displayed conservation among groups of coexpressed and marker genes (Belgard et al, 2013). Our comparative transcriptomic analysis allowed us to critically evaluate recent studies of the avian brain that compared a relatively small number of genes (Dugas‐Ford et al, 2012; Suzuki et al, 2012; Montiel and Molnár, 2013). Indeed, our data suggest there are genes that, if selected, could be used to support many different relationships (Montiel and Molnár, 2013; Fig.…”

“…This serves as a substrate for further innovations that produced neocortical expansion (Smart et al, 2002; Dehay et al, 2015). Comparisons of circuits, analysis of cell lineage, and gene expression patterns between avian and mammalian brains reveals that cells originating from different lineages can develop convergent gene networks evolving to integrate into functional circuits (Dugas‐Ford et al, 2012; Suzuki et al, 2012; Belgard and Montiel, 2013; Belgard et al, 2013; Fournier et al, 2015)…”

Evolution of the forebrain — revisiting the pallium

“…(For supplementary histological materials, see http://Wiley.Biolucida.net/ JCN521-16Jarvis_Chen). The patterns of expression largely confirm (see also Dugas-Ford et al, 2012) the pallial nature of many of the structures situated ventral to the lateral ventricle, which classical neuroanatomists had considered to be subpallial. More importantly, the current studies demonstrate that several subventricular populations are topologically continuous with, and share molecular expression properties with, populations situated above the lateral ventricle suggesting an origin from a common embryonic cytological field.…”