multicolor VNO.png
 

Genes, circuits and behavior

Neurobiology of social behavior

THE ISOGAI LAB AT THE SAINSBURY WELLCOME CENTRE

 

The Isogai lab is located at Sainsbury Wellcome Centre for Neural Circuits and Behaviour, University College London.

 

Our lab uses molecular and systems neuroscience approaches to uncover the molecular underpinnings of neural circuit functions and to tackle two major questions in neuroscience:

1) How are social cues, including pheromones, detected and processed in the brain?

2) How do genes control neural circuit homeostasis, modulation, and reprogramming?

We are developing cutting-edge methods that enable us to tackle these questions from unique perspectives. Especially, we will focus on social behavior as a fascinating model to delineate the links between genes, circuits and complex natural behaviors. We thereby aim to attain a detailed understanding of the molecular and neural basis for how external stimuli impact the physiology and behavior of animals.

Please read on below for more details.

 

PROJECTS

 

We focus on two main themes in the lab:

1) Pheromones and social behavior

Social behavior, a complex repertoire of natural behaviors directed towards members of the same species, is absolutely essential for animal societies. Understanding how individuals perceive and process social signals, which eventually leads to specific behavioral actions, remains a challenging problem.

We study the social behavior of mice as a robust system to achieve a detailed understanding of complex natural behaviors. The house mouse (Mus musculus) is not only an excellent genetic model organism, but also relies heavily on scents, or pheromones, to guide its behavior. By dissecting pheromone actions in the brain, we can then study the neural circuits underlying innate behaviors such as mating, territorial aggression, social hierarchy, defensive behaviors as well as innate fear. We will systematically examine how specific pheromones trigger dynamic responses in the brain. We thereby aim to gain significant insights on how social information is processed in the brain and regulates behaviors.

We have so far uncovered specific receptor neurons that detect pheromone cues, some of which we found are critical for specific social and defensive behaviors. In the future, we will continue to ask an outstanding question: how does the detection of pheromonal cues trigger specific behavioral actions? At the SWC, we will combine cutting edge molecular, imaging and physiology methods to tackle this question.

Recommended reading for beginners:

Dulac and Torello (2003) Molecular detection of pheromone signals in mammals: from genes to behaviour, Nature Reviews Neuroscience

Isogai et al. (2011) Molecular organisation of vomeronasal chemoreception, Nature

Lorentz (1952) King Solomon's Ring

Tinbergen (1951) The Study of Instinct

Wyatt (2014) Pheromones and animal behavior : chemical signals and signatures, 2nd Ed.

 

Our work covered by popular press:

Rosen (2012) Scent into action: Rodent responses to a whiff of predator may offer clues to instinct in the brain, Science News

Bates (2102) Passing the sniff test, HHMI bulletin (contains a link to interesting videos)

Welsh (2011) Fight or Flight: How the Nose Knows What to Do, Livescience

 

2) Gene regulation in neural circuits

A rather remarkable property of neurons -- and the brain -- is their ability to tune themselves to a changing sensory world. The extensive array of experience-dependent processes described to date pinpoints the critical involvement of molecular changes at the synapse and in the cell nucleus. A fascinating question is how these molecular processes are coordinately controlled at the level of neural circuits. Importantly, how genes are controlled at single cell level within a complex tissue environment is a fundamental question in biology.

Specifically, we aim to address the following basic questions:

1) How does a neuron coordinately regulate transcription of the key cell-type specific genes that determine biophysical properties?

2) How do neurons within a functional circuit “communicate” transcriptionally?

The dissection of gene regulation in vivo at single-cell resolution has been technically challenging. Using the lab’s expertise in single-cell biochemistry of transcription, we aim to develop novel methods to monitor and perturb gene expression in neural tissues and to uncover the gene expression programs underlying circuit homeostasis, modulation and reprogramming.