Adolescence and “Late Blooming” Synapses of the Prefrontal Cortex

Abstract

The maturation of the prefrontal cortex (PFC) during adolescence is thought to be important for cognitive and affective development and mental health risk. Whereas many summaries of adolescent development have focused on dendritic spine pruning and gray matter thinning in the PFC during adolescence, we highlight recent rodent data from our laboratory and others to call attention to continued synapse formation and plasticity in the adolescent period in specific cell types and circuits. In particular, we highlight changes in inhibitory neurotransmission onto intratelencephalic (IT-type) projecting cortical neurons and late expansion of connectivity between the amygdala and PFC and the ventral tegmental area and PFC. Continued work on these "late blooming" synapses in specific cell types and circuits, and their interrelationships, will illuminate new opportunities for understanding and shaping the biology of adolescent development. We also address which aspects of adolescent PFC development are dependent on pubertal processes.

Signatures of sex: Sex differences in gene expression in the vertebrate brain

“…During adolescence, the brain undergoes significant synaptic pruning which extends into the twenties in humans and P35-45 in rodents (Figure 1). Connectivity within the mesolimbic reward pathway continues to develop and is modulated by hormone signaling (reviewed in Walker et al, 2017;Delevich, Wren Thomas, & Wilbrecht, 2019). This pathway intersects with social behavior circuitry to modulate sex differences in motivated behaviors such as parenting, sexual behavior, threat avoidance, and intake of drugs of abuse (Becker, 2009;Gee et al, 2018;O'Connell & Hofmann, 2011).…”

Adolescent maturation of the prefrontal cortex: Role of stress and sex in shaping adult risk for compromise

“…The adult brain is shaped in part by an increase in pruning and decrease in overall synaptic number that is initiated with the transition from juvenile development to the beginning of the adolescent timeframe (Figure ). From birth through adolescence, gray matter of the brain decreases in a process known as cortical thinning . The decrease in cortical gray matter is due to the pruning of synapses, encompassing a normal decrease in axo‐dendritic, axo‐axonal and axo‐somatic connections that are maintained through experience and activity.…”

“…The decrease in cortical gray matter is due to the pruning of synapses, encompassing a normal decrease in axo‐dendritic, axo‐axonal and axo‐somatic connections that are maintained through experience and activity. The rate of change differs within the PFC, with layer V cells showing more hormone‐insensitive pruning than cells that reside in layer II/III . An in‐depth review of these differences in the dynamic nature of changes in the synaptic connections in the PFC has been recently published by Delevich et al and Zimmermann et al…”

“…From birth through adolescence, gray matter of the brain decreases in a process known as cortical thinning. [68][69][70][71] The decrease in cortical gray matter is due to the pruning of synapses, encompassing a normal decrease in axo-dendritic, axo-axonal and axo-somatic connections that are maintained through experience and activity. The rate of change differs within the PFC, with layer V cells F I G U R E 1 Development within the prefrontal cortex (PFC), in a process that is conserved in mammals, continues throughout adolescence.…”

“…67) showing more hormone-insensitive pruning than cells that reside in layer II/III. 68 An in-depth review of these differences in the dynamic nature of changes in the synaptic connections in the PFC has been recently published by Delevich et al 68 and Zimmermann et al 71 Recent studies have suggested a sex difference in synaptic pruning of the PFC during adolescence. Female rats appear to have an earlier peak in synapses than males which could alter the window of sensitivity to exposures between the sexes.…”