Project Summary/Abstract Brain function requires coordinated activation of specific networks engaged in systems that process information in localised and distributed manners. In order to develop such specific networks, the brain engages groups of neurons that fire together in ensembles that can be observed with calcium imaging. Patterns of spontaneous activity in the cerebral cortex are thought to enable the formation of circuits specialised for processing different types of sensory information. How the brain first switches on activity across areas is unknown. I propose to investigate exactly how and when in fetal life these patterns first occur in vivo, what regulates their development, and how they shape neural circuits and later brain function. A major barrier to addressing this question has been that patterns of activity such as patchwork-type activity in S1 and travelling waves in V1 are present at birth in rodents making it difficult to study this question in vivo as the brain apparently switches on before birth. To address this, I propose to apply modern scientific tools and technologies to an Australian marsupial mammal: the fat-tailed dunnart (S. crassicaudata; Dasyuridae), thereby developing a new approach for investigating brain development. Dunnarts are small (adults weigh ~15g), carnivorous animals whose pups (joeys) are born at an equivalent stage of development to embryonic day 10 in mouse or seven-week gestation in humans, and therefore most of their brain development occurs as they develop inside their mother's pouch. Despite this more primitive developmental phase, dunnarts have a six-layered cerebral cortex which is similar to a mouse but with advantageous exceptions such as a more advanced binocular visual system. Dunnarts are also able to solve complex configurable problems and learn quickly. To ensure feasibility of this project, I provide evidence that we can use targeted electroporation to introduce sensitive calcium indicators such as GCaMP6S into the cortex. In preliminary experiments we find that patchwork-type activity in S1 and traveling waves in V1 are evolutionarily conserved in dunnarts, motivating this new direction of my research to understand the development and function of these patterns of spontaneous activity. Having access to study the entire genesis and development of these patterns enables longitudinal studies that can link cells, circuits and behavior/function. The creation of longitudinal imaging capabilities bridging micro/meso/macro scales as well as awake behavior across the lifespan will be required in order to identify which neuronal cell types initiate spontaneous synchronous activity and whether these activity patterns are instructive in forming functionally-specific circuits. I will also explore how spontaneous activity in the cortex evolves throughout life as circuits begin to function to mediate sensory experience and behavioural reactions. I ensembles knowledge propose that by understanding the fundamental processes r equired to build of patterned activity in the brain and how these affect behavior, this work will advance our of the neural basis of mental experience.

Project Narrative The project presents a new approach to studying mammalian brain development. The proposal is to apply modern molecular tools and new behavioural assays in a mouse-sized marsupial that is born at stage 18 (equivalent to human seven-week gestation) and develops further in their mother's pouch. Longitudinal studies in this model will provide unprecedented access to study the functional and behavioural outcomes of fetal disruptions to circuitry and could be applied to test therapeutic interventions.