Interrogation of the role of transient interneuron circuits in the development of normal sensory activity in vivo.

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A major obstacle to our understanding of brain function is the sheer diversity and number of cells that contribute to even the simplest of behaviours. One approach aims to tackle this problem by investigating the rules that govern the developing brain. The reasoning being that if we can understand the biology going on at early stages - processes that lay the foundations for the amazing processing power of our brains - then we can perhaps extrapolate them to the more complex adult brain. A further advantage of this approach is that it allows us to study and dissect the relative contribution of genetics and environment on brain formation, both of which combine to sculpt an individual's unique perception of the world. Yet even at these formative stages, amongst all the millions of nerve cells jostling for position there remains the question as to how an individual nerve cell in the developing brain know where to go and which other nerve cells it should form connections to? One particular cell type - local, inhibitory nerve cells termed interneurons, face a monumental task as their origin is completely distinct from their eventual site of function. To get round this challenge it appears that the migration and integration of these cells into the correct brain circuits is governed largely by genetic events. In essence they represent 'hard-wired' components of the circuit. Ongoing studies in the lab suggest that this is the case. We have used the power of genetics to interrogate the contribution of interneurons to emergent brain circuits and through these studies have revealed that certain subtypes of interneuron act as a scaffold for the developing brain, constraining the impact of the environment so that no matter what our early life experience are, should we have the right genetic programmes, our brain will end up with being 'normal'. Moreover just like a scaffold these particular interneuron circuits are transient and so we cannot study them in the adult brain. Unfortunately from then on the story is still largely incomplete and we have a limited knowledge of what function these interneurons actually have in the newborn brain. We believe that resolving this is critically important because this activity lays the foundation for all of our subsequent cognitive development. As such we want to determine (1) the exact contribution of interneurons to formative brain activity in the normal brain. We want to see if our scaffold interneurons change function as the brain develops; (2) we want to test if this scaffold is critical. We will achieve this by blocking formation of the scaffold by using genetics to promote the mature brain state earlier in development; before (3) altering directly the performance of the transient network at discrete stages through development and assessing the consequences on network maturation. Our belief is that the latter will demonstrate the importance of this early transient interneuron circuit to normal brain development.