The goal of this project is to investigate the neural substrates of the maturation process that takes place around puberty and which is associated with the development of a key cognitive ability, working memory. The prefrontal cortex, a part of the brain greatly expanded in primates compared to other vertebrates, undergoes a long maturation process that extends through puberty and into early adulthood. This process mirrors the development of higher cognitive functions. A number of mental illnesses have onsets linked to the maturation of the prefrontal cortex, most notably schizophrenia, which manifests itself in early adulthood. Executive function also improves in adulthood, and inadequate development of this capacity is associated with delinquency and other conditions of health and social significance. Little is known about the physiological changes that the prefrontal cortex undergoes in adolescence so as to mediate increased cognitive control. Taking advantage of recent methodological and conceptual advances, we propose to investigate the changes of prefrontal cortical physiology that occur after puberty. We propose to use a non-human primate model that will allow us to conduct neurophysiological recordings in the prefrontal cortex of peri-pubertal and adult animals. Our study will make use of monkeys trained to perform behavioral tasks that test working memory ability. Experiments will record neuronal activity related to task performance to understand what neural variables maturate after the onset of puberty. These experiments will offer insights on how development of the prefrontal cortex alters its physiological responses, findings that will be essential for understanding and treating mental illnesses thought to be associated with a failure of prefrontal cortical maturation.

Public Health Relevance

The proposed research will determine how the functions of prefrontal cortex neurons change between adolescence and adulthood. Knowledge drawn from these experiments will elucidate the development of higher cognitive processes such as working memory, which is necessary for understanding the biological basis of conditions such as Attention Deficit Disorder and mental illnesses such as schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH116675-02
Application #
9771534
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Buhring, Bettina D
Project Start
2018-08-28
Project End
2023-06-30
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157