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How does evolution build a complex brain?

The neocortex is that portion of the brain that is involved in volitional motor control, perception, cognition, and a number of other complex behaviors exhibited by mammals, including humans. Indeed, the increase in the size of the cortical sheet and cortical field number is one of the hallmarks of human brain evolution. Fossil records and comparative studies of the neocortex indicate that early mammalian neocorticies were composed of only a few parts or cortical fields, and that in some lineages such as primates, the neocortex expanded dramatically. More significantly, the number of cortical fields increased and the connectivity between cortical fields became more complex. While we do not know the exact transformation between this type of increase in cortical field number and connectivity, and the emergence of complex behaviors like those mentioned above, we know that species that have large neocorticies with multiple parts generally have more complex behaviors, both overt and covert. While a number of inroads have been made into understanding how neurons in the neocortex respond to avariety of stimuli, the micro and macro circuitry of particular neocortical fields, and the molecular developmental events that construct current organization, very little is known about how more cortical fields are added in evolution. In particular, we do not know the rules of change, nor the constraints imposed on evolving nervous systems that dictate the particular phenotype that will ultimately emerge.

One reason why these issues are unresolved is that the brain is a compromise between existing genetic constraints, and the need to adapt. Thus, the functions that the brain generates are absolutely imperfect, although functionally optimized. This makes it very difficult to determine the rules of construction, to generate viable computational models of brain evolution, and to predict the direction of changes that may occur over time. Despite these obstacles, it is still possible to study the evolution of the neocortex. One way is to study the products of the evolutionary process, extant mammal brains, and to make inferences about the process. We have successfully used this comparative approach in a variety of mammals to generate a number of theories regarding how the process of evolution generates a complex neocortex. The second way to study brain evolution is to examine the developmental mechanisms that give rise to complex brains. The series of experiments proposed here are designed to test the theories regarding cortical evolution, generated from comparative studies, by “tweaking” in a developing nervous system what we believe is naturally being modified in evolution. Our goals are to identify the constraints imposed on the evolving neocortex, to disentangle the genetic and activity dependent mechanisms that give rise to complex brains, and ultimately to produce a cortical phenotype that is consistent with what would naturally occur in evolution.

There are three types of experiments planned. The first is to increase the size of the cortical sheet in the developing marsupial brain (Monodelphis domestica, and to examine the resulting cortex using electrophysiological recording techniques, neuroanatomical tracing methods, and molecular techniques. We know that an increase in the size of the cortical sheet is a necessary step in generating a complex brain, but we do not know if it is sufficient to induce new cortical fields to form. These experiments will allow us to appreciate if cortical fields simply get larger, or if new fields are added when the cortical sheet size is increased. The second type of experiment will be to examine the extent to which changes in peripheral morphology, and the patterned activity they generate can alter the cortical phenotype. In these experiments, peripheral
manipulations in the form of ablations and transplants will be done, and the resulting cortex examined using electrophysiological recording techniques, neuroanatomical tracing methods, and molecular techniques.

The final experiment will be to examine the spatial and temporal pattern of selected genes in two highly derived animals, the echo-locating bat and the naked mole rat, and to compare these patterns with those of the mouse. These animals have a small cortical sheet, like the mouse, but the organization of cortical fields on the sheet is vastly different. These differences are related to changes in their peripheral morphology and associated use. Patterns of gene expression will be examined prior to and after the arrival of thalamocortical afferents, which carry patterned activity from peripheral sensory receptor arrays. Studying highly derived animals offers an ideal opportunity to appreciate the genetic and activity dependent mechanisms that contribute to cortical field construction in an exaggerated form.