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Rewiring the brain

Posted by , on 3 January 2014

Watching animals, with their vast diversity of complex behaviours, can never be boring. In the animals around us, ants, spiders, lizards, dogs, cats, fish, birds…, we see so many different modes of locomotion, nesting, foraging and hunting in both solitary and social forms. Peculiar moves of appendages, bobbing of heads, unique calls and colours make up elaborate courtship or aggressive rituals, and animals have the most curious parenting styles. Underlying all these behaviours is a unique nervous system in every animal and I have been interested in how nervous systems develop. I use the fruitfly, Drosophila melanogaster, to understand this because of the phenomenal genetics available in this model organism.

I work in K. VijayRaghavan’s lab at the National Centre for Biological Sciences – TIFR in India and in collaboration with Heinrich Reichert at the Biozetrum, University of Basel in Switzerland. I was studying the role of a particular gene in the development of the fly’s olfactory system when I noticed something odd. Flies mutant for this gene seemed to have some extra neurons in the olfactory circuit. Where did these neurons come from?  We had many hypotheses that we rigorously tested. We finally worked out that this gene is normally expressed in a set of neurons in the fly’s higher brain centre. When mutant, these neurons transformed completely and became olfactory neurons!  They changed the way they looked, the neurotransmitter they expressed and even their enhancer activity profile. The extent of this transformation led us to wonder if these neurons were functional in the olfactory circuit or not.  Did they make functional synapses with other olfactory neurons and respond to odour stimuli?

We teamed up with Jing Wang’s lab in UCSD, where with Deshou Cao (a postdoctoral fellow there) we decided to test this. We did two kinds of experiments together. Odour information is brought into the brain by the sensory neurons. We reasoned that if the transformed neurons do form functional synapses, they should be postsynaptic to the sensory neurons. We used a calcium sensitive activity indicator, GCaMP, to measure the activity in the transformed neurons while we stimulated the sensory neurons either electrically or by puffing odours at the sensory neurons. To our excitement, we found that in both cases, the transformed neurons responded robustly to the stimuli! This meant that the transformed neurons were functional in the olfactory circuit.

This is very exciting because it is one of very few examples where a single gene can change the identity of neurons so completely and dramatically and therefore have an impact on the assembly of functional neural circuits in the central brain. We are now writing this story up for publication.

I have the Company of Biologist to thank for making a large part of this possible.  California, with its bustling and excellent science, balmy weather and breathtaking countryside is a very exciting place to be in. But it is also extremely expensive! We would have found it very difficult to complete this story were it not for the support that the Company of Biologists’ travelling fellowship provided.  So I want to offer my sincerest thanks and gratitude to the COB, and especially to the wonderful and helpful team of people at the COB.

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One thought on “Rewiring the brain”

  1. Exciting read. I am a science communicator based in Kolkata, India. Is it possible to elaborate the latter part of the story starting from the UCSD collaboration? I am not asking for further details…just a little bit more explanation. Thanks!

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