Vertebrate brains and evolutionary connectomics: on the origins of the mammalian 'neocortex'

Abstract

The organization of the non-mammalian forebrain had long puzzled neurobiologists. Unlike typical mammalian brains, the telencephalon is not organized in a laminated 'cortical' manner, with distinct cortical areas dedicated to individual sensory modalities or motor functions. The two major regions of the telencephalon, the basal ventricular ridge (BVR) and the dorsal ventricular ridge (DVR), were loosely referred to as being akin to the mammalian basal ganglia. The telencephalon of non-mammalian vertebrates appears to consist of multiple 'subcortical' groups of cells. Analysis of the nuclear organization of the avian brain, its connections, molecular properties and physiology, and organization of its pattern of circuitry and function relative to that of mammals, collectively referred to as 'evolutionary connectomics', revealed that only a restricted portion of the BVR is homologous to the basal ganglia of mammals. The remaining dorsal regions of the DVR, wulst and arcopallium of the avian brain contain telencephalic inputs and outputs remarkably similar to those of the individual layers of the mammalian 'neocortex', hippocampus and amygdala, with instances of internuclear connections strikingly similar to those found between cortical layers and within radial 'columns' in the mammalian sensory and motor cortices. The molecular properties of these 'nuclei' in birds and reptiles are similar to those of the corresponding layers of the mammalian neocortex. The fundamental pathways and cell groups of the auditory, visual and somatosensory systems of the thalamus and telencephalon are homologous at the cellular, circuit, network and gene levels, and are of great antiquity. A proposed altered migration of these homologous neurons and circuits during development is offered as a mechanism that may account for the altered configuration of mammalian telencephalae.

Keywords: auditory; birds; microcircuitry; nuclear to laminar transformation; radial columns; reptiles.

Figure 1.

Pre-1969 ‘classic view’ of avian (a) and mammalian (b) brain relationships. Individual brain regions are coloured according to the earlier concepts of the homologous relationships of each general brain regions. Note that the vast majority of the avian telencephalon was considered to be homologous to the mammalian basal ganglia and claustrum. This concept was based exclusively on studies of non-experimental material. There was no information regarding regions of the avian forebrain that were involved in processing clearly defined sensory/motor information in a manner comparable to that performed by the mammalian cortices. (c,d) ‘Modern view’ of avian and mammalian brain relationships according to the proposal of the Avian Brain Nomenclature Forum, largely based on the formulation proposed by Karten [6]. Note that based on an expanding body of experimental material, only a limited portion of the telencephalon is now considered to be homologous to the mammalian basal ganglia. As in mammals, the major portion of the dorsal telencephalon contains discrete components to various pallial derivatives, including those homologous to cortex, hippocampus, claustrum and amygdala. Well-defined auditory, visual and somatosensory fields are now well recognized in birds and non-avian reptiles (modified from [9]).

Figure 2.

Neurons in the nuclei of the avian DVR are homologous to neurons in layers of mammalian cortex. Although differing in macroarchitecture, the basic cell types and connections of sensory input and output neurons of (a) avian/reptilian and (b) mammalian telencephalon are nearly identical, most notably lacking the familiar pyramidal cell morphology. The populations receiving sensory input and the output neurons of both regions express the same genes found in the sensory recipient and output laminae of mammalian neocortex as indicated by the colour code of genes and layers [13]. In birds and other non-mammalian vertebrates, individual laminae were often disposed as distinct nuclei, particularly within the large intraventricular expansion of the dorsal ventricular ridge (DVR). The cell clusters share properties with individual layers of the mammalian sensory cortex, particularly the auditory and tectofugal visual sensory cortex of the temporal lobe. In mammals, the homologous neurons are found in laminae, a characteristic feature of mammalian neocortex. The major change that may have occurred with the evolution of mammals is an altered pattern of migration of these cell groups from the DVR into laminae in the dorsolateral pallium. In birds, a separate pallial region, the dorsomedial ‘wulst’ or ‘bump’ shares many properties with the mammalian striate cortex, though with the output layer lying most externally. In contrast, the basal ganglia occupy similar location, connections, relative volume and molecular properties in all classes of vertebrates and appear to have experienced few changes over the past 535 million years. Aiv, arcopallium intermedium; BG, basal ganglia; DVR, dorsal ventricular ridge; Hp, hippocampus; Spt, septum; St Ctx, striate cortex; V, ventricle; Wulst, ‘bump’ homologous to mammalian striate cortex; WhM, white matter; EAG2 and RORbeta, genes commonly expressed in sensory neurons of layer 4; ER81 and PCP4, genes commonly express in output neurons of layers 5b-6 of cortex.

Figure 3.

Comparable laminar and columnar organization of the avian auditory pallium (a) and the mammalian AI auditory cortex (b). Note that this schematic drawing illustrates only the major components of this intricate network. The microanatomy is now also supported by recent molecular analyses of the profiles of the corresponding populations, as well as electrophysiological studies by Calabrese and Woolley [21] (Illustration based on [20]).

Figure 4.

Schematic of the postulated difference between non-mammalian (a) and mammalian (b) forms with respect to the ontogenetic derivation of neurons composing the pallial mantle. In both forms, numerous pallial neurons are proliferated in embryonic development by the ependyma of the mantle proper (arrows 1 and 2). Only short stretches of the continuous ependymal lining of the cerebral ventricle have been indicated (in black). It is suggested in the text that the mammalian neocortex results from an augmentation of the intrinsic pallial cell population by neuroblasts proliferated by the ependyma of the dorsal ventricular ridge (DVR, arrow 3 in b); the corresponding proliferation in non-mammalian forms produces the DVR (arrows 3, in a). The striatal complex of the non-mammalian brain and the caudoputamen-globus pallidus of the mammal are indicated by vertical shading; the non-mammalian external striatum is shown by cross-hatching. DVR, dorsal ventricular ridge; IC, internal capsule; LFB, lateral forebrain bundle [15].

Figure 5.

Schematic of a parasagittal section through the brains of birds (a,b), a teleost fish (c), and a rodent (d), showing the relative location of the lateral ventricle (blue) in relation to neural populations homologous to the mammalian cortex (green) and subpallial domains (magenta). In mammals (d), the cortex (pallium) lies entirely above the ventricle, which led early anatomists to consider the entire region below the ventricle in birds to be subpallial (a). Studies since 1969 [5] have shown that cortical-equivalent cell groups lie both above and below the lateral ventricle (b) and its extension (blue dotted line) suggesting that the lateral ventricle is not a useful demarcation between pallial (cortex) and subpallial (striatopallidal) fields. The situation in teleosts (c) is even more extreme where the telencephalic ventricle is covered by the membranous tela choroidea and lies entirely dorsal of the telencephalic neuronal populations. The detailed organization and homologies of pallial cell groups in teleosts remains to be elucidated. More extensive arrays of gene expression data and details of connectivity are necessary in order to discern the full organization of the forebrain in ray-finned fishes. Panels (a,b) are adapted from Jarvis et al. [28]; panel (c) is adapted from [34]; panel (d) is based on the Allen Brain Atlas (http://mouse.brain-map.org). (Adapted from [17].)