Dataset Information

Strength and Diversity of Inhibitory Signaling Differentiates Primate Anterior Cingulate from Lateral Prefrontal Cortex.

ABSTRACT: The lateral prefrontal cortex (LPFC) and anterior cingulate cortex (ACC) of the primate play distinctive roles in the mediation of complex cognitive tasks. Compared with the LPFC, integration of information by the ACC can span longer timescales and requires stronger engagement of inhibitory processes. Here, we reveal the synaptic mechanism likely to underlie these differences using in vitro patch-clamp recordings of synaptic events and multiscale imaging of synaptic markers in rhesus monkeys. Although excitatory synaptic signaling does not differ, the level of synaptic inhibition is much higher in ACC than LPFC layer 3 pyramidal neurons, with a significantly higher frequency (?6×) and longer duration of inhibitory synaptic currents. The number of inhibitory synapses and the ratio of cholecystokinin to parvalbumin-positive inhibitory inputs are also significantly higher in ACC compared with LPFC neurons. Therefore, inhibition is functionally and structurally more robust and diverse in ACC than in LPFC, resulting in a lower excitatory: inhibitory ratio and a greater dynamic range for signal integration and network oscillation by the ACC. These differences in inhibitory circuitry likely underlie the distinctive network dynamics in ACC and LPC during normal and pathological brain states.SIGNIFICANCE STATEMENT The lateral prefrontal cortex (LPFC) and anterior cingulate cortex (ACC) play temporally distinct roles during the execution of cognitive tasks (rapid working memory during ongoing tasks and long-term memory to guide future action, respectively). Compared with LPFC-mediated tasks, ACC-mediated tasks can span longer timescales and require stronger engagement of inhibition. This study shows that inhibitory signaling is much more robust and diverse in the ACC than in the LPFC. Therefore, there is a lower excitatory: inhibitory synaptic ratio and a greater dynamic range for signal integration and oscillatory behavior in the ACC. These significant differences in inhibitory synaptic transmission form an important basis for the differential timing of cognitive processing by the LPFC and ACC in normal and pathological brain states.

SUBMITTER: Medalla M

PROVIDER: S-EPMC5426565 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Strength and Diversity of Inhibitory Signaling Differentiates Primate Anterior Cingulate from Lateral Prefrontal Cortex.

Medalla Maria M Gilman Joshua P JP Wang Jing-Yi JY Luebke Jennifer I JI

The Journal of neuroscience : the official journal of the Society for Neuroscience 20170405 18

The lateral prefrontal cortex (LPFC) and anterior cingulate cortex (ACC) of the primate play distinctive roles in the mediation of complex cognitive tasks. Compared with the LPFC, integration of information by the ACC can span longer timescales and requires stronger engagement of inhibitory processes. Here, we reveal the synaptic mechanism likely to underlie these differences using <i>in vitro</i> patch-clamp recordings of synaptic events and multiscale imaging of synaptic markers in rhesus monk ...[more]

PMID: 28381592

Similar Datasets

Project description:Regional cellular heterogeneity is a fundamental feature of the human neocortex; however, details of this heterogeneity are still undefined. We used single-nucleus RNA-sequencing to examine cell-specific transcriptional features in the dorsolateral PFC (DLPFC) and the subgenual anterior cingulate cortex (sgACC), regions implicated in major psychiatric disorders. Droplet-based nuclei-capture and library preparation were performed on replicate samples from 8 male donors without history of psychiatric or neurologic disorder. Unsupervised clustering identified major neural cell classes. Subsequent iterative clustering of neurons further revealed 20 excitatory and 22 inhibitory subclasses. Inhibitory cells were consistently more abundant in the sgACC and excitatory neuron subclusters exhibited considerable variability across brain regions. Excitatory cell subclasses also exhibited greater within-class transcriptional differences between the two regions. We used these molecular definitions to determine which cell classes might be enriched in loci carrying a genetic signal in genome-wide association studies or for differentially expressed genes in mental illness. We found that the heritable signals of psychiatric disorders were enriched in neurons and that, while the gene expression changes detected in bulk-RNA-sequencing studies were dominated by glial cells, some alterations could be identified in specific classes of excitatory and inhibitory neurons. Intriguingly, only two excitatory cell classes exhibited concomitant region-specific enrichment for both genome-wide association study loci and transcriptional dysregulation. In sum, by detailing the molecular and cellular diversity of the DLPFC and sgACC, we were able to generate hypotheses on regional and cell-specific dysfunctions that may contribute to the development of mental illness.SIGNIFICANCE STATEMENT Dysfunction of the subgenual anterior cingulate cortex has been implicated in mood disorders, particularly major depressive disorder, and the dorsolateral PFC, a subsection of the PFC involved in executive functioning, has been implicated in schizophrenia. Understanding the cellular composition of these regions is critical to elucidating the neurobiology underlying psychiatric and neurologic disorders. We studied cell type diversity of the subgenual anterior cingulate cortex and dorsolateral PFC of humans with no neuropsychiatric illness using a clustering analysis of single-nuclei RNA-sequencing data. Defining the transcriptomic profile of cellular subpopulations in these cortical regions is a first step to demystifying the cellular and molecular pathways involved in psychiatric disorders.

Dataset Information

Strength and Diversity of Inhibitory Signaling Differentiates Primate Anterior Cingulate from Lateral Prefrontal Cortex.

Publications

Strength and Diversity of Inhibitory Signaling Differentiates Primate Anterior Cingulate from Lateral Prefrontal Cortex.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets