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Published on: June 9, 2021
Functional maturation of excitatory synapses in layer 3 pyramidal neurons during postnatal development of the primate
Guillermo Gonzalez-Burgos1, Sven Kroener, Aleksey V Zaitsev
1Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA15261, USA. gburgos@pitt.edu
Insights
Synaptic pruning in the primate brain
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Primate Brain Research
Background:
- The primate dorsolateral prefrontal cortex (DLPFC) undergoes significant synaptic pruning during adolescence.
- This refinement of neural circuits is linked to improved working memory but its functional implications are unclear.
- Understanding which synapses are pruned is key to understanding adolescent brain maturation.
Purpose of the Study:
- To investigate the functional properties of excitatory synapses in the primate DLPFC during postnatal development.
- To determine if synapses eliminated during adolescence are functionally immature.
- To differentiate between maturation-dependent and maturation-independent synaptic pruning mechanisms.
Main Methods:
- Electrophysiological recordings were used to assess excitatory synaptic function in monkey DLPFC.
- Key synaptic properties studied included release probability, AMPA/NMDA ratio, and NMDA current duration.
- Sensitivity to NR2B subunit-selective antagonists was also examined.
Main Results:
- Early postnatal monkeys (3 months) exhibited immature synaptic properties (high release probability, low AMPA/NMDA ratio, prolonged NMDA currents).
- These immature properties were associated with greater sensitivity to ifenprodil, an NR2B antagonist.
- Synaptic inputs in preadolescent (15 months) and adult monkeys showed similar functional properties, indicating maturation before adolescence.
Conclusions:
- Functionally immature synapses are significantly reduced in the DLPFC before the onset of adolescence.
- Synaptic pruning during DLPFC adolescence may not involve widespread changes in synaptic strength.
- Adolescent circuit refinement in the DLPFC appears to prune synapses that have already matured or possess other maturation-independent characteristics.
Abstract:
In the primate dorsolateral prefrontal cortex (DLPFC), the density of excitatory synapses decreases by 40-50% during adolescence. Although such substantial circuit refinement might underlie the adolescence-related maturation of working memory performance, its functional significance remains poorly understood. The consequences of synaptic pruning may depend on the properties of the eliminated synapses. Are the synapses eliminated during adolescence functionally immature, as is the case during early brain development? Or do maturation-independent features tag synapses for pruning? We examined excitatory synaptic function in monkey DLPFC during postnatal development by studying properties that reflect synapse maturation in rat cortex. In 3-month-old (early postnatal) monkeys, excitatory inputs to layer 3 pyramidal neurons had immature properties, including higher release probability, lower alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/N-methyl-D-aspartate (NMDA) ratio, and longer duration of NMDA-mediated synaptic currents, associated with greater sensitivity to the NMDA receptor subunit B (NR2B) subunit-selective antagonist ifenprodil. In contrast, excitatory synaptic inputs in neurons from preadolescent (15 months old) and adult (42 or 84 months old) monkeys had similar functional properties. We therefore conclude that the contribution of functionally immature synapses decreases significantly before adolescence begins. Thus, remodeling of excitatory connectivity in the DLPFC during adolescence may occur in the absence of widespread maturational changes in synaptic strength.
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