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Sainsbury Wellcome Centre for Neural Circuits and Behaviour

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Isogai Group

Molecular genetics of behaviour – genes’ perspective of brain function
Yoh Isogai

Yoh Isogai
Senior Research Fellow
email: y.isogai@ucl.ac.uk
tel: +44 20 3108 8018

Research Area
A fascinating question in biology is how genes orchestrate not only the body plan but also complex physiological responses to the environment and experience. The central nervous system represents an elaborate example in which the genome programs a network of cells to perform the computations necessary for individual behaviours. Furthermore, gene regulation serves as one of the fundamental modes by which animals’ experiences and internal states modify neural circuit operations. Our laboratory’s goal is to obtain a principal logic by which genes operate to control neural circuits by uncovering “genomic codes” that allow circuits to change upon experiences and adapt to the environment. We study social behaviours, genetically hardwired yet highly flexible and experience-dependent, as a model linking gene activities to the control of neural circuits and behaviour.

Research Topics

A diversity of vomeronasal neurons. Each colour marks unique chemosensory receptor mRNAs expressed in these cells.

1) The social brain
Rodents rely heavily on special scents known as pheromones for social information such as species, gender, and social status. An important insight from classical ethology is that many animals use a specific set of discrete stimuli to trigger social behaviours such as aggression and mating. We are interested in uncovering which specific sensory inputs, olfactory and non-olfactory, can activate these innate circuits and how combinations of these specific stimuli are reconstituted as social information in the brain. To tackle this problem, we use a combination of molecular biology, biochemistry, genomics and physiology to understand how animals perceive their social environments. Our studies so far have uncovered specific chemosensory receptors that control specific social and defensive behaviours including pup-directed behaviours and predator defense. These findings will now allow us to identify specific population of brain cells critical for these behaviours. Importantly, the recognition of social cues are prominently affected in human disorders of social behaviours, and our studies will shed light on the circuit basis of social recognition and its regulation at the molecular level.

Transcription of an activity dependent gene (in red) in the olfactory bulb. Blue marks cell nucleus.

2) Logic of gene regulation in the brain
A remarkable property of the brain is that neuronal networks are highly plastic upon experiences. Pioneering studies in invertebrates and vertebrates showed that molecular changes that occur within synapses and cell nuclei, as well as the actions of neuromodulators, can “reprogram” existing neural circuits. In fact, while it is widely appreciated that neural activation and inhibition accompany unique transcriptional changes, it has been difficult to attain a clear logic by which these transcriptional changes are linked to the performance of the circuit as a whole. To tackle this question, we need substantially improved tools to probe and control gene expression in brain tissues. We have, for example, pioneered a system to dissect the mechanisms of transcription at the biochemical level in single cells in Drosophila. Building on these methods we will continue to develop and use advanced imaging techniques, such as single molecule, cleared tissue, and/or live microscopy, to probe mechanisms of gene regulation in heterogeneous tissues such as the brain in a quantitative fashion. With an increasing appreciation that neuronal cell types classified physiologically, anatomically, and transcriptionally determine the functions of each neuron type within a circuit, our goal is to uncover the regulatory logic of how a single genome can produce diverse neuronal cell types and tune their properties on demand.

Group Members
Selected Publications