Epub – Neuroscience
Laminar Differences in the Targeting of Dendritic Spines by Cortical Pyramidal Neurons and Interneurons in Human Dorsolateral Prefrontal Cortex
Glausier JR, Datta D, Fish KN, Chung DW, Melchitzky DS, Lewis DA
Activation of specific neural circuits in different layers of the primate dorsolateral prefrontal cortex (DLPFC) is essential for working memory, a core cognitive function. Recurrent excitation between pyramidal neurons in middle and deep layers of the DLPFC contributes to the laminar-specific activity associated with different working memory subprocesses. Excitation between cortical pyramidal neurons is mediated by glutamatergic synapses on dendritic spines, but whether the relative abundance of spines receiving cortical inputs differs between middle and deep cortical layers in human DLPFC is unknown. Additionally, GABAergic inputs to spines sculpt pyramidal neuron activity. Whether dendritic spines that receive a glutamatergic input from a cortical pyramidal neuron are targeted by GABAergic interneurons in the human DLPFC is unknown. Using triple-label fluorescence confocal microscopy, we found that 1) the density of spines receiving an input from a cortical pyramidal neuron is greater in the middle than in the deep laminar zone, 2) dendritic spines dually innervated by a cortical pyramidal neuron and an interneuron are present in the human DLPFC, and 3) the density of spines dually innervated by a cortical pyramidal neuron and an interneuron is also greater in the middle than in the deep laminar zone. Ultrastructural analyses support the presence of spines that receive a cortical pyramidal neuron synapse and an interneuron synapse in human and monkey DLPFC. These data support the notion that the DLPFC middle laminar zone is particularly endowed with a microcircuit structure that supports the gating, integrating and fine-tuning of synaptic information in recurrent excitatory microcircuits.
Glausier JR, Datta D, Fish KN, Chung DW, Melchitzky DS, Lewis DA. Laminar Differences in the Targeting of Dendritic Spines by Cortical Pyramidal Neurons and Interneurons in Human Dorsolateral Prefrontal Cortex. Neuroscience. 2020 Nov 16:S0306-4522(20)30682-5. doi: 10.1016/j.neuroscience.2020.10.022. [Epub ahead of print] PMID: 33212224.
Laboratory of David A. Lewis, MD
Researching the neural circuitry of the prefrontal cortex and related brain regions, and the alterations of this circuitry in schizophrenia.
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UPMC Western Psychiatric Hospital
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