Location: Bowdoin / Calendar


How to maintain a variable brain

  • 5/1/2014 | 4:00 PM – 5:00 PM
  • Location: Druckenmiller Hall, Room 020
  • Event Type: Seminar

How to maintain a variable brain

Timothy O'Leary, Post Doctoral Researcher, Volen Center for Complex Systems, Brandeis University

How to maintain a variable brain

Imagine you are an engineer who is given the following task: design an airplane that has all its spare parts on board and that can have every single one of its parts replaced between take-off and landing. No engineer would want such a challenging design project and no pilot would want to fly such a plane, yet this is the challenge faced by the neurons that make up our nervous system. Even though each neuron lives for many years, the components it is made from are replaced over the course of weeks, days or even hours. Yet our brains and bodies continue to function throughout this process. How does our nervous system keep functioning with this continual rebuilding going on? This is the central question of the work I will present.

Neurons are examples of electrically excitable cells, other examples include the cells that make up the heart and muscle tissue. Just like the components of an airplane, electrically excitable cells have a diverse range of specialized properties and generate specific patterns of activity that are important physiologically. All excitable cells have many thousands (or millions) of molecular 'gates' called ion channels that open and close, allowing ions to flow in and out of the cell. The different ion channel types have different gating properties and are encoded in different genes. Just as the variety of paints used by an artist can be mixed to form new hues, combinations of many different types of ion channels work together to give each excitable cell its overall properties. For example, the balance of different amounts of ion channels determine the rate at which a neuron fires, or the size and speed of a muscle contraction. It is therefore very important that the balance of ion channels is set appropriately in each cell, otherwise the electrical activity can become uncoordinated, or lost altogether. This is what happens in diseases such as epilepsy, and many kinds of respiratory, motor and heart diseases.

I used what is known about this internal monitoring and rebuilding to make a theoretical model of ion channel regulation in neurons. This has helped us understand how neurons (and other excitable cells) can monitor their own activity and self-regulate their ion channel expression. One thing we learned is that cells with very similar properties in the self-regulating model can nonetheless have quite different underlying ion channel expression. This is consistent with experimental observations, which show that even genetically identical cells can have very different amounts of ion channels expressed in their membranes. We also discovered that certain pathologies (such as hyperexcitability at one extreme, or loss of activity at the other) can actually be caused by the cell's internal control system. Therefore, to understand and cure some diseases, we need to pick apart and understand how biological systems control their internal properties when they are in a normal, healthy state.