Distinct Properties of Layer 3 Pyramidal Neurons from Prefrontal and Parietal Areas of the Monkey Neocortex

Abstract

In primates, working memory function depends on activity in a distributed network of cortical areas that display different patterns of delay task-related activity. These differences are correlated with, and might depend on, distinctive properties of the neurons located in each area. For example, layer 3 pyramidal neurons (L3PNs) differ significantly between primary visual and dorsolateral prefrontal (DLPFC) cortices. However, to what extent L3PNs differ between DLPFC and other association cortical areas is less clear. Hence, we compared the properties of L3PNs in monkey DLPFC versus posterior parietal cortex (PPC), a key node in the cortical working memory network. Using patch-clamp recordings and biocytin cell filling in acute brain slices, we assessed the physiology and morphology of L3PNs from monkey DLPFC and PPC. The L3PN transcriptome was studied using laser microdissection combined with DNA microarray or quantitative PCR. We found that in both DLPFC and PPC, L3PNs were divided into regular spiking (RS-L3PNs) and bursting (B-L3PNs) physiological subtypes. Whereas regional differences in single-cell excitability were modest, B-L3PNs were rare in PPC (RS-L3PN:B-L3PN, 94:6), but were abundant in DLPFC (50:50), showing greater physiological diversity. Moreover, DLPFC L3PNs display larger and more complex basal dendrites with higher dendritic spine density. Additionally, we found differential expression of hundreds of genes, suggesting a transcriptional basis for the differences in L3PN phenotype between DLPFC and PPC. These data show that the previously observed differences between DLPFC and PPC neuron activity during working memory tasks are associated with diversity in the cellular/ molecular properties of L3PNs.

Ketamine disrupts naturalistic coding of working memory in primate lateral prefrontal cortex networks

“…One possibility is that changes in the architecture of LPFC circuits, such as expansion of layers 2/3 and increase in the size and number of spines on pyramidal cells with an abundance of NMDARs, makes the LPFC more vulnerable to the effects of ketamine relative to other areas. Indeed, the density of dendritic spines in pyramidal cells is higher in LPFC relative to LIP [ 38 ]. Although systemic administration of a drug may produce similar concentrations across brain vascular networks, idiosyncrasies in receptor distribution and their molecular regulation may allow heterogeneity of dose dependent local effects [ 39 ].…”

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

“…The D2 network controls the connection to the hippocampal system (Tomasella et al, 2018;Khlghatyan et al, 2019). Species related differences in this circuitry could be large, so human data are needed for the correct interpretation of the results (Gonzalez-Burgos et al, 2019). The cortical D2 mediated effects of the most common antipsychotics (antagonists and partial agonists) have been extensively evaluated.…”

The Subcortical-Allocortical- Neocortical continuum for the Emergence and Morphological Heterogeneity of Pyramidal Neurons in the Human Brain

“…Besides conserved basic principles of mammalian brain development, evolution also produced significant quantitative and qualitative changes in cell number and shape along with circuit organization in cortical areas ( Geschwind and Rakic, 2013 ; see also Herculano-Houzel et al, 2008 ; Herculano-Houzel, 2019 ). The connectivity of pyramidal dendrites in cortical multimodal areas, which receive a broad range of inputs at hierarchically higher association levels of integrative processing, show longer, more branched, and have more spines than in areas that process a specific modality of motor or primary sensory activity ( Jacobs et al, 2001 ; Anderson et al, 2009 ; Kolb and Whishaw, 2015 ; Hrvoj-Mihic et al, 2017 ; González-Burgos et al, 2019 ). Moreover, cortical pyramidal neurons developed basal and apical dendritic domains with different synaptic receptive fields ( Larriva-Sahd, 2002 ; Andersen et al, 2007 ; Spruston, 2008 ; Spruston et al, 2013 ; Larriva-Sahd, 2014 ).…”