Abstract
Background
In schizophrenia, layer 3 pyramidal neurons (L3PNs) of the dorsolateral prefrontal
cortex exhibit deficits in markers of excitatory synaptic inputs that are thought
to disrupt the patterns of neural network activity essential for cognitive function.
These deficits are usually interpreted under Irwin Feinberg’s hypothesis of altered
synaptic pruning, which postulates that normal periadolescent pruning, thought to
preferentially eliminate weak/immature synapses, is altered in schizophrenia. However,
it remains unknown whether periadolescent pruning on L3PNs in the primate dorsolateral
prefrontal cortex selectively eliminates weak excitatory synapses or uniformly eliminates
excitatory synapses across the full distribution of synaptic strengths.
Methods
To distinguish between these alternative models of synaptic pruning, we assessed the
densities of dendritic spines, the site of most excitatory inputs to L3PNs, and the
distributions of excitatory synaptic strengths in dorsolateral prefrontal cortex L3PNs
from male and female monkeys across the periadolescent period of synaptic pruning.
We used patch-clamp methods in acute brain slices to record miniature excitatory synaptic
currents and intracellular filling with biocytin to quantify dendritic spines.
Results
On L3PNs, dendritic spines exhibited the expected age-related decline in density,
but mean synaptic strength and the shape of synaptic strength distributions remained
stable with age.
Conclusions
The absence of age-related differences in mean synaptic strength and synaptic strength
distributions supports the model of a uniform pattern of synaptic pruning across the
full range of synaptic strengths. The implications of these findings for the pathogenesis
and functional consequences of dendritic spine deficits in schizophrenia are discussed.
Keywords
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Article info
Publication history
Published online: January 31, 2023
Accepted:
January 23,
2023
Received in revised form:
January 6,
2023
Received:
October 10,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
YN is currently affiliated with the Department of Psychiatry, Nara Medical University School of Medicine, Kashihara, Japan.
Identification
Copyright
© 2023 Society of Biological Psychiatry.
