Insights into the Neurobiology of Behavioral Inhibition from Nonhuman Primate Models.

Children with extreme behavioral inhibition (BI) are at a significantly greater risk to develop anxiety disorders later in life. We and others have identified similar early-life temperamental BI in nonhuman primates (NHPs), including rhesus monkeys. NHP models of BI provide a unique opportunity to study the neurobiology of BI in a species that shares biological, developmental, and socioemotional similarities with humans.

Understanding the heterogeneity of anxiety using a translational neuroscience approach.

Anxiety disorders affect millions of people worldwide and present a challenge in neuroscience research because of their substantial heterogeneity in clinical presentation. While a great deal of progress has been made in understanding the neurobiology of fear and anxiety, these insights have not led to effective treatments. Understanding the relationship between phenotypic heterogeneity and the underlying biology is a critical first step in solving this problem.

Brief postnatal exposure to bisphenol A affects apoptosis and gene expression in the medial prefrontal cortex and social behavior in rats with sex specificity.

Bisphenol A (BPA) is an endocrine disruptor found in polycarbonate plastics and exposure in humans is nearly ubiquitous and it has widespread effects on cognitive, emotional, and reproductive behaviors in both humans and animal models. In our laboratory we previously found that perinatal BPA exposure results in a higher number of neurons in the adult male rat prefrontal cortex (PFC) and less play in adolescents of both sexes. Here we examine changes in the rate of postnatal apoptosis in the rat prefrontal cortex and its timing with brief BPA exposure.

Impact of pubertal onset on region-specific Esr2 expression.

In female rats, pubertal onset is associated with maturation of the medial prefrontal cortex (mPFC) and mPFC-mediated behaviours. These behavioural and anatomical changes are likely a result of the effects of oestrogens at the nuclear oestrogen receptor (ER)β, which is expressed at higher levels than the ERα isoform in the adult mPFC. Researchers have previously quantified ERβ protein and Esr2 RNA in rodents during early postnatal development and adulthood, although an adolescent-specific trajectory of this receptor in the mPFC has not been documented.

Cell death in the male and female rat medial prefrontal cortex during early postnatal development.

Apoptosis, programmed cell death, is a critical component of neurodevelopment occurring in temporal, spatial, and at times, sex-specific, patterns across the cortex during the early postnatal period. During this time, the brain is particularly susceptible to environmental influences that are often used in animal models of neurodevelopmental disorders. In the present study, the timing of peak cell death was assessed by the presence of pyknotic cells in the male and female rat medial prefrontal cortex (mPFC), a cortical region that in humans, is often involved in developmental disorders.

Adolescent stress during, but not after, pubertal onset impairs indices of prepulse inhibition in adult rats.

Exposure to stress during adolescence is a risk factor for developing several psychiatric disorders, many of which involve prefrontal cortex (PFC) dysfunction. The human PFC and analogous rodent medial prefrontal cortex (mPFC) continue to mature functionally and anatomically during adolescence, and some of these maturational events coincide with pubertal onset. As developing brain regions are more susceptible to the negative effects of stress, this may make puberty especially vulnerable.

The structural reorganization of the prefrontal cortex during adolescence as a framework for vulnerability to the environment.

Adolescence is a time of increased vulnerability to developing substance use disorders. In part, this may be due to the wide array of neural changes occurring during this time, many of which can be altered by environmental stimuli including drugs. In this review, we will examine the evidence for neuroanatomical changes during adolescence in the prefrontal cortex (PFC), an important neural region involved in decision making and reward processing.

Cortical reorganization during adolescence: What the rat can tell us about the cellular basis.

The human cortex, particularly the prefrontal cortex, decreases in volume during adolescence which indicates considerable pruning. There is consistent evidence from human, monkey and rat tissue that synapses, dendritic spines and dendrites are pruned during this time. However, our work with a rat model of adolescence shows that other cellular components are remodeling at this time as well.

Influences of age and pubertal status on number and intensity of perineuronal nets in the rat medial prefrontal cortex.

The prefrontal cortex (PFC) is a late developing region of the cortex, and its protracted maturation during adolescence may confer a period of plasticity. Closure of critical, or sensitive, periods in sensory cortices coincides with perineuronal net (PNN) expression, leading to enhanced inhibitory function and synaptic stabilization. PNN density has been found to increase across adolescence in the male rat medial PFC (mPFC).

Behavioral effects in adult rats exposed to low doses of a phthalate mixture during the perinatal or adolescent period.

Hormones influence neurodevelopment which can result in vulnerability to endocrine disruptors such as phthalates during both the perinatal period and adolescence. Using a rat model, we have previously shown that perinatal exposure to an environmentally relevant phthalate mixture at low doses results in cognitive flexibility deficits in adults and a reduction in neuron and synapse number within the medial prefrontal cortex. Here, we further examined the behavioral effects of exposure to an environmentally relevant mixture of phthalates at low doses during either perinatal development or adolescence.

Synaptic number changes in the medial prefrontal cortex across adolescence in male and female rats: A role for pubertal onset.

Adolescence is a unique period of development, marked by maturation of the prefrontal cortex (PFC), a region important for executive functioning. During this time, the human PFC decreases in overall volume and thickness. Likewise in adolescent rodents, losses of neurons, dendrites, dendritic spines and neurotransmitter receptors have been documented within the medial prefrontal cortex (mPFC), sometimes with sex and layer specificity.

A role for puberty in water maze performance in male and female rats.

Adolescence is characterized by neuroanatomical changes that coincide with increased cognitive performance. This developmental period is particularly important for the medial prefrontal cortex (mPFC), which mediates higher-order cognitive functioning. The authors' laboratory has shown that puberty is associated with sex-specific changes in neuron number and the dendritic tree in the rat mPFC, but the effects of pubertal onset on cognitive performance remain relatively unexplored.