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Developing optogenetics/electrophysiology applications for studying cognitive impairment during stress

Background

The prefrontal cortex (PFC) is a very important brain region. It plays a vital role in working memory - cognitive tasks such as temporarily remembering a 7-digit number while making a phone call. Stress impairs cognition in otherwise healthy people and dramatically worsens cognitive dysfunction in mental disorders, including depression and attention-deficit hyperactivity disorders (ADHD). A large body of evidence from animal and human studies suggests that stress changes the chemistry of the brain, and as a result interferes with the networks of brain cells (neurons) in the PFC.

The Problem

One particular group of neurons in the PFC produces a neurotransmitter called corticotropin releasing hormone (CRH). Evidence has already shown that CRH impairs working memory in the PFC. We believe that stress induces the CRH-producing neurons to release CRH, impairing cognition and working memory. We do not currently have evidence of this mechanism, however. CRH neurons are only one type of neuron in the PFC, so distinguishing their firing from the firing of other neurons is not possible, and the amount of CRH produced is too small to be measured by typical means.

The Project

We will develop cutting-edge techniques to:

* precisely measure and artificially manipulate the activity of CRH neurons in the PFC, and

* measure small and local releases of CRH by these neurons.

The success of our project will open the door to understand the neural mechanisms for how stress impairs cognitive functions and how it may contribute to mental disorders.

Western Researchers Wataru Inoue Brian Allman Julio Martinez-Trujillo

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