Adolescence is a unique transitional time, long noted for emotional turmoil, increased vulnerability to addiction and the onset of psychiatric disorders such as depression and schizophrenia. The neural restructuring that occurs at this time may result in increased vulnerability to the environment including stress. The prefrontal cortex of humans, in particular, decreases in size during adolescence with different timing and slope of trajectories in each sex (Lenroot et al, 2007). This means that the cellular basis for the size decrease must also differ between males and females. Pruning of neurons, dendrites, synapses and receptors occurs in the prefrontal cortex during adolescence in humans and other species (Huttenlocher, 1979;Lewis, 1997;Andersen et al, 2000;Markham et al, 2007), and there are indications of sex differences in pruning in the rare instances where they have been examined. The timing of pruning will be investigated here in Aim 1, and the implications of sex differences in this timing will be tested with stress in Aim 2. Stress during human adolescence is a known predisposition for psychopathology and can precipitate symptoms (Grant et al, 2004;Arnsten, 2011) which indicates a disruption of normal pruning. There are sex differences in the behavioral reaction to stress in adolescents (Romeo;2010;Wilkin et al, 2012). This may contribute to the incidence and severity of schizophrenia during adolescent onset (1.4:1 male>female) as well as in the lifetime occurrence of depressive disorders (2:1 female>male) (Abel et al, 2010;Parker &Brotchie, 2010). Thus sex and stress interact in the sculpting of potentially vulnerable circuits during adolescence. Our long-term goal is to understand how the neural changes during adolescence can go awry to precipitate psychopathologies in a sexually dimorphic pattern. The central hypothesis of the present proposal is that there are sex differences in the timing of pruning during adolescence that result in differential vulnerabilitiesto stress.

Public Health Relevance

Adolescence is often the time of mental disorder onset, and there are sex differences in the incidence of these disorders. Sex differences in the timing of the cellular changes occurring in the cortex during adolescence will be investigated here in a rat model. The vulnerability of these changes to stress, a precipitating factor in mental illness, will be tested by applying stress a different time points in adolescence in both sexes.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Special Emphasis Panel (ZMH1-ERB-L (07))
Program Officer
Simmons, Janine M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Illinois Urbana-Champaign
Schools of Arts and Sciences
United States
Zip Code
Willing, Jari; Cortes, Laura R; Brodsky, Joseph M et al. (2017) Innervation of the medial prefrontal cortex by tyrosine hydroxylase immunoreactive fibers during adolescence in male and female rats. Dev Psychobiol 59:583-589
Walker, Deena M; Bell, Margaret R; Flores, Cecilia et al. (2017) Adolescence and Reward: Making Sense of Neural and Behavioral Changes Amid the Chaos. J Neurosci 37:10855-10866
Juraska, Janice M; Willing, Jari (2017) Pubertal onset as a critical transition for neural development and cognition. Brain Res 1654:87-94
Drzewiecki, Carly M; Willing, Jari; Juraska, Janice M (2016) Synaptic number changes in the medial prefrontal cortex across adolescence in male and female rats: A role for pubertal onset. Synapse 70:361-8
Willing, Jari; Drzewiecki, Carly M; Cuenod, Bethany A et al. (2016) A role for puberty in water maze performance in male and female rats. Behav Neurosci 130:422-7
Koss, Wendy A; Lloyd, Madeline M; Sadowski, Renee N et al. (2015) Gonadectomy before puberty increases the number of neurons and glia in the medial prefrontal cortex of female, but not male, rats. Dev Psychobiol 57:305-12
Willing, J; Juraska, J M (2015) The timing of neuronal loss across adolescence in the medial prefrontal cortex of male and female rats. Neuroscience 301:268-75
Koss, Wendy A; Belden, Chelsea E; Hristov, Alexander D et al. (2014) Dendritic remodeling in the adolescent medial prefrontal cortex and the basolateral amygdala of male and female rats. Synapse 68:61-72