Rodrigo Suárez

Evolution and development of interhemispheric connections in the vertebrate forebrain.

Axonal connections between the left and right sides of the brain are crucial for bilateral integration of lateralized sensory, motor, and associative functions. Throughout vertebrate species, forebrain commissures share a conserved developmental plan, a similar position relative to each other within the brain and similar patterns of connectivity. However, major events in the evolution of the vertebrate brain, such as the expansion of the telencephalon in tetrapods and the origin of the six-layered isocortex in mammals, resulted in the emergence and diversification of new commissural routes. These new interhemispheric connections include the pallial commissure, which appeared in the ancestors of tetrapods and connects the left and right sides of the medial pallium (hippocampus in mammals), and the corpus callosum, which is exclusive to eutherian (placental) mammals and connects both isocortical hemispheres. A comparative analysis of commissural systems in vertebrates reveals that the emergence of new commissural routes may have involved co-option of developmental mechanisms and anatomical substrates of preexistent commissural pathways. One of the embryonic regions of interest for studying these processes is the commissural plate, a portion of the early telencephalic midline that provides molecular specification and a cellular scaffold for the development of commissural axons. Further investigations into these embryonic processes in carefully selected species will provide insights not only into the mechanisms driving commissural evolution, but also regarding more general biological problems such as the role of developmental plasticity in evolutionary change.

Balanced Interhemispheric Cortical Activity Is Required for Correct Targeting of the Corpus Callosum

Bilateral integration of sensory and associative brain processing is achieved by precise connections between homologous regions in the two hemispheres via the corpus callosum. These connections form postnatally, and unilateral deprivation of sensory or spontaneous cortical activity during a critical period severely disrupts callosal wiring. However, little is known about how this early activity affects precise circuit formation. Here, using in utero electroporation of reporter genes, optogenetic constructs, and direct disruption of activity in callosal neurons combined with whisker ablations, we show that balanced interhemispheric activity, and not simply intact cortical activity in either hemisphere, is required for functional callosal targeting. Moreover, bilateral ablation of whiskers in symmetric or asymmetric configurations shows that spatially symmetric interhemispheric activity is required for appropriate callosal targeting. Our findings reveal a principle governing axon targeting, where spatially balanced activity between regions is required to establish their appropriate connectivity.

Mutual influences between the main olfactory and vomeronasal systems in development and evolution

The sense of smell plays a crucial role in the sensory world of animals. Two chemosensory systems have been traditionally thought to play-independent roles in mammalian olfaction. According to this, the main olfactory system (MOS) specializes in the detection of environmental odorants, while the vomeronasal system (VNS) senses pheromones and semiochemicals produced by individuals of the same or different species. Although both systems differ in their anatomy and function, recent evidence suggests they act synergistically in the perception of scents. These interactions include similar responses to some ligands, overlap of telencephalic connections and mutual influences in the regulation of olfactory-guided behavior. In the present work, we propose the idea that the relationships between systems observed at the organismic level result from a constant interaction during development and reflects a common history of ecological adaptations in evolution. We review the literature to illustrate examples of developmental and evolutionary processes that evidence these interactions and propose that future research integrating both systems may shed new light on the mechanisms of olfaction.

Heterogeneities of size and sexual dimorphism between the subdomains of the lateral-innervated accessory olfactory bulb (AOB) of Octodon degus (Rodentia: Hystricognathi).

The vomeronasal system (VNS) of rodents participates in the regulation of a variety of social and sexual behaviours related to semiochemical communication. All rodents studied so far possess two parallel pathways from the vomeronasal organ (VNO) to the accessory olfactory bulb (AOB). These segregated afferences express either Gi2 or Go protein alpha-subunits and innervate the rostral or caudal half of the AOB, respectively. In muroid rodents, such as rats and mice, both subdivisions of the AOB are of similar proportions; as there is no anatomical feature indicative of the segregation, histochemical detection has been required to portray its boundary. We studied the AOB of Octodon degus, a diurnal caviomorph rodent endemic to central Chile, and found several distinctive traits not reported in a rodent before: (i) the vomeronasal nerve innervates the AOB from its lateral aspect, in opposition to the medial innervation described in rabbits and muroids, (ii) an indentation that spans all layers delimits the boundary between the rostral and caudal AOB subdivisions (rAOB and cAOB, respectively), (iii) the rAOB is twice the size of the cAOB and features more and larger glomeruli, and (iv) the rAOB, but not the cAOB, shows male-biased sexual dimorphisms in size and number of glomeruli, while the cAOB, but not the rAOB, shows a male-biased dimorphism in mitral cell density. The heterogeneities we describe here within AOB subdomains suggest that these segregated regions may engage in distinct operationalities. We discuss our results in relation to conspecific semiochemical communication in O. degus, and present it as a new animal model for the study of VNS neurobiology and evolution.

Cognitive ecology in hummingbirds: the role of sexual dimorphism and its anatomical correlates on memory.

In scatter-hoarding species, several behavioral and neuroanatomical adaptations allow them to store and retrieve thousands of food items per year. Nectarivorous animals face a similar scenario having to remember quality, location and replenishment schedules of several nectar sources. In the green-backed firecrown hummingbird (Sephanoides sephanoides), males are territorial and have the ability to accurately keep track of nectar characteristics of their defended food sources. In contrast, females display an opportunistic strategy, performing rapid intrusions into males territories. In response, males behave aggressively during the non-reproductive season. In addition, females have higher energetic demands due to higher thermoregulatory costs and travel times. The natural scenario of this species led us to compared cognitive abilities and hippocampal size between males and females. Males were able to remember nectar location and renewal rates significantly better than females. However, the hippocampal formation was significantly larger in females than males. We discuss these findings in terms of sexually dimorphic use of spatial resources and variable patterns of brain dimorphisms in birds.

Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum

The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of callosal axons is dependent upon the prior remodeling and degradation of the intervening interhemispheric fissure. This remodeling event is initiated by astroglia on either side of the interhemispheric fissure, which intercalate with one another and degrade the intervening leptomeninges. Callosal axons then preferentially extend over these specialized astroglial cells to cross the midline. A key regulatory step in interhemispheric remodeling is the differentiation of these astroglia from radial glia, which is initiated by Fgf8 signaling to downstream Nfi transcription factors. Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis.

Deterioration of the Gαo vomeronasal pathway in sexually dimorphic mammals.

In mammals, social and sexual behaviours are largely mediated by the vomeronasal system (VNS). The accessory olfactory bulb (AOB) is the first synaptic locus of the VNS and ranges from very large in Caviomorph rodents, small in carnivores and ungulates, to its complete absence in apes, elephants, most bats and aquatic species. Two pathways have been described in the VNS of mammals. In mice, vomeronasal neurons expressing Gαi2 protein project to the rostral portion of the AOB and respond mostly to small volatile molecules, whereas neurons expressing Gαo project to the caudal AOB and respond mostly to large non-volatile molecules. However, the Gαo-expressing pathway is absent in several species (horses, dogs, musk shrews, goats and marmosets) but no hypotheses have been proposed to date to explain the loss of that pathway. We noted that the species that lost the Gαo pathway belong to Laurasiatheria and Primates lineages, both clades with ubiquitous sexual dimorphisms across species. To assess whether similar events of Gαo pathway loss could have occurred convergently in dimorphic species we studied G-protein expression in the AOB of two species that independently evolved sexually dimorphic traits: the California ground squirrel Spermophilus beecheyi (Rodentia; Sciurognathi) and the cape hyrax Procavia capensis (Afrotheria; Hyracoidea). We found that both species show uniform expression of Gαi2-protein throughout AOB glomeruli, while Gαo expression is restricted to main olfactory glomeruli only. Our results suggest that the degeneration of the Gαo-expressing vomeronasal pathway has occurred independently at least four times in Eutheria, possibly related to the emergence of sexual dimorphisms and the ability of detecting the gender of conspecifics at distance.

Shared and differential traits in the accessory olfactory bulb of caviomorph rodents with particular reference to the semiaquatic capybara

The vomeronasal system is crucial for social and sexual communication in mammals. Two populations of vomeronasal sensory neurons, each expressing Gαi2 or Gαo proteins, send projections to glomeruli of the rostral or caudal accessory olfactory bulb, rAOB and cAOB, respectively. In rodents, the Gαi2‐ and Gαo‐expressing vomeronasal pathways have shown differential responses to small/volatile vs. large/non‐volatile semiochemicals, respectively. Moreover, early gene expression suggests predominant activation of rAOB and cAOB neurons in sexual vs. aggressive contexts, respectively. We recently described the AOB of Octodon degus, a semiarid‐inhabiting diurnal caviomorph. Their AOB has a cell indentation between subdomains and the rAOB is twice the size of the cAOB. Moreover, their AOB receives innervation from the lateral aspect, contrasting with the medial innervation of all other mammals examined to date. Aiming to relate AOB anatomy with lifestyle, we performed a morphometric study on the AOB of the capybara, a semiaquatic caviomorph whose lifestyle differs remarkably from that of O. degus. Capybaras mate in water and scent‐mark their surroundings with oily deposits, mostly for male–male communication. We found that, similar to O. degus, the AOB of capybaras shows a lateral innervation of the vomeronasal nerve, a cell indentation between subdomains and heterogeneous subdomains, but in contrast to O. degus the caudal portion is larger than the rostral one. We also observed that four other caviomorph species present a lateral AOB innervation and a cell indentation between AOB subdomains, suggesting that those traits could represent apomorphies of the group. We propose that although some AOB traits may be phylogenetically conserved in caviomorphs, ecological specializations may play an important role in shaping the AOB.

Development of body, head and brain features in the Australian fat-tailed dunnart (Sminthopsis crassicaudata; Marsupialia: Dasyuridae); A postnatal model of forebrain formation

Most of our understanding of forebrain development comes from research of eutherian mammals, such as rodents, primates, and carnivores. However, as the cerebral cortex forms largely prenatally, observation and manipulation of its development has required invasive and/or ex vivo procedures. Marsupials, on the other hand, are born at comparatively earlier stages of development and most events of forebrain formation occur once attached to the teat, thereby permitting continuous and non-invasive experimental access. Here, we take advantage of this aspect of marsupial biology to establish and characterise a resourceful laboratory model of forebrain development: the fat-tailed dunnart (Sminthopsis crassicaudata), a mouse-sized carnivorous Australian marsupial. We present an anatomical description of the postnatal development of the body, head and brain in dunnarts, and provide a staging system compatible with human and mouse developmental stages. As compared to eutherians, the orofacial region develops earlier in dunnarts, while forebrain development is largely protracted, extending for more than 40 days versus ca. 15 days in mice. We discuss the benefits of fat-tailed dunnarts as laboratory animals in studies of developmental biology, with an emphasis on how their accessibility in the pouch can help address new experimental questions, especially regarding mechanisms of brain development and evolution.

Evolution of Telencephalic Commissures: Conservation and Change of Developmental Systems in the Origin of Brain Wiring Novelties

Connections between the left and right brain hemispheres, known as commissures, are essential for coordinating everyday sensory-motor and cognitive functions. Across vertebrates, telencephalic commissures share a similar organization, likely due to highly conserved events of early brain development. However, lineage-specific novelties in commissural systems have also occurred, including axonal rerouting through preexistent tracts, and the origin and expansion of new tracts, such as the corpus callosum. This chapter discusses the phylogenetic history of telencephalic commissures, the possible developmental scenarios involved in the evolution of commissural innovations, and the potential applications of an evolutionary developmental approach to human brain research.