Comparing the development of cortex-wide gene expression patterns between two species in a common reference frame.

Advances in sequencing techniques have made comparative studies of gene expression a current focus for understanding evolutionary and developmental processes. However, insights into the spatial expression of genes have been limited by a lack of robust methodology. To overcome this obstacle, we developed methods and software tools for quantifying and comparing tissue-wide spatial patterns of gene expression within and between species. Here, we compare cortex-wide expression of RZRß and Id2 mRNA across early postnatal development in mice and voles. We show that patterns of RZRß expression in neocortical layer 4 are highly conserved between species but develop rapidly in voles and much more gradually in mice, who show a marked expansion in the relative size of the putative primary visual area across the first postnatal week. Patterns of Id2 expression, by contrast, emerge in a dynamic and layer-specific sequence that is consistent between the two species. We suggest that these differences in the development of neocortical patterning reflect the independent evolution of brains, bodies, and sensory systems in the 35 million years since their last common ancestor.

Coevolution of motor cortex and behavioral specializations associated with flight and echolocation in bats.

Bats have evolved behavioral specializations that are unique among mammals, including self-propelled flight and echolocation. However, areas of motor cortex that are critical in the generation and fine control of these unique behaviors have never been fully characterized in any bat species, despite the fact that bats compose ∼25% of extant mammalian species. Using intracortical microstimulation, we examined the organization of motor cortex in Egyptian fruit bats (Rousettus aegyptiacus), a species that has evolved a novel form of tongue-based echolocation.1,2 We found that movement representations include an enlarged tongue region containing discrete subregions devoted to generating distinct tongue movement types, consistent with their behavioral specialization generating active sonar using tongue clicks. This magnification of the tongue in motor cortex is comparable to the enlargement of somatosensory representations in species with sensory specializations.3-5 We also found a novel degree of coactivation between the forelimbs and hindlimbs, both of which are involved in altering the shape and tension of wing membranes during flight. Together, these findings suggest that the organization of motor cortex has coevolved with peripheral morphology in bats to support the unique motor demands of flight and echolocation.

Phenotypic Alterations in Cortical Organization and Connectivity across Different Time Scales.

In the following review, we describe the types of phenotypic changes to the neocortex that occur over the longer time scale of evolution, and over the shorter time scale of an individual lifetime. To understand how phenotypic variability emerges in the neocortex, it is important to consider the cortex as part of an integrated system of the brain, the body, the environment in which the brain and body develops and evolves, and the affordances available within a particular environmental context; changes in any part of this brain/body/environment network impact the neocortex. We provide data from comparative studies on a wide variety of mammals that demonstrate that body morphology, the sensory epithelium, and the use of a particular morphological structure have a profound impact on neocortical organization and connections. We then discuss the genetic and epigenetic factors that contribute to the development of the neocortex, as well as the role of spontaneous and sensory driven activity in constructing a nervous system. Although the evolution of the neocortex cannot be studied directly, studies in which developmental processes are experimentally manipulated provide important insights into how phenotypic transformations could occur over the course of evolution and demonstrate that relatively small alterations to the body and/or the environment in which an individual develops can manifest as large changes to the neocortex. Finally, we discuss how these phenotypic alterations to the neocortex impact an important target of selection - behavior.

Kinematic analysis of sensorimotor behavior during variable ladder rung walking in short-tailed opossums (Monodelphis domestica).

This protocol presents a workflow for detecting differences in kinematics between experimental conditions. It is tailored for short-tailed opossums but can be applied to any species capable of completing the ladder rung task. There are four phases of this protocol: (1) data collection, (2) pose tracking, (3) analysis of single trials, and (4) cross-condition comparisons. This pipeline implements aspects of machine learning and signal processing, allowing for rapid data analysis that provides insight into how animals perform this task. For complete details on the use and execution of this protocol, please refer to Englund et al. (2020).

Available Sensory Input Determines Motor Performance and Strategy in Early Blind and Sighted Short-Tailed Opossums.

The early loss of vision results in a reorganized neocortex, affecting areas of the brain that process both the spared and lost senses, and leads to heightened abilities on discrimination tasks involving the spared senses. Here, we used performance measures and machine learning algorithms that quantify behavioral strategy to determine if and how early vision loss alters adaptive sensorimotor behavior. We tested opossums on a motor task involving somatosensation and found that early blind animals had increased limb placement accuracy compared with sighted controls, while showing similarities in crossing strategy. However, increased reliance on tactile inputs in early blind animals resulted in greater deficits in limb placement and behavioral flexibility when the whiskers were trimmed. These data show that compensatory cross-modal plasticity extends beyond sensory discrimination tasks to motor tasks involving the spared senses and highlights the importance of whiskers in guiding forelimb control.

Distributed Motor Control of Limb Movements in Rat Motor and Somatosensory Cortex: The Sensorimotor Amalgam Revisited.

Which areas of the neocortex are involved in the control of movement, and how is motor cortex organized across species? Recent studies using long-train intracortical microstimulation demonstrate that in addition to M1, movements can be elicited from somatosensory regions in multiple species. In the rat, M1 hindlimb and forelimb movement representations have long been thought to overlap with somatosensory representations of the hindlimb and forelimb in S1, forming a partial sensorimotor amalgam. Here we use long-train intracortical microstimulation to characterize the movements elicited across frontal and parietal cortex. We found that movements of the hindlimb, forelimb, and face can be elicited from both M1 and histologically defined S1 and that representations of limb movement types are different in these two areas. Stimulation of S1 generates retraction of the contralateral forelimb, while stimulation of M1 evokes forelimb elevation movements that are often bilateral, including a rostral region of digit grasping. Hindlimb movement representations include distinct regions of hip flexion and hindlimb retraction evoked from S1 and hip extension evoked from M1. Our data indicate that both S1 and M1 are involved in the generation of movement types exhibited during natural behavior. We draw on these results to reconsider how sensorimotor cortex evolved.