Genetic Feedback Regulation of Frontal Cortical Neuronal Ensembles Through Activity-Dependent Arc Expression and Dopaminergic Input
| Autor: | Surjeet Mastwal, Vania Y. Cao, Kuan Hong Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Nerve net Cognitive Neuroscience Neuroscience (miscellaneous) Nerve Tissue Proteins Motor Activity Feedback regulation lcsh:RC321-571 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Arc/Arg3.1 Dopamine medicine Animals lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry development Cognitive deficit Regulation of gene expression Feedback Physiological learning neuronal ensembles Dopaminergic frontal cortical circuits Sensory Systems Frontal Lobe Cytoskeletal Proteins 030104 developmental biology medicine.anatomical_structure activity-dependent genetic feedback Frontal lobe Gene Expression Regulation Perspective neuromodulation Developmental plasticity medicine.symptom Nerve Net dopamine Psychology Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Frontiers in Neural Circuits Frontiers in Neural Circuits, Vol 10 (2016) |
| ISSN: | 1662-5110 |
| DOI: | 10.3389/fncir.2016.00100 |
| Popis: | Mental functions involve coordinated activities of specific neuronal ensembles that are embedded in complex brain circuits. Aberrant neuronal ensemble dynamics is thought to form the neurobiological basis of mental disorders. A major challenge in mental health research is to identify these cellular ensembles and determine what molecular mechanisms constrain their emergence and consolidation during development and learning. Here, we provide a perspective based on recent studies that use activity-dependent gene Arc/Arg3.1 as a cellular marker to identify neuronal ensembles and a molecular probe to modulate circuit functions. These studies have demonstrated that the transcription of Arc is activated in selective groups of frontal cortical neurons in response to specific behavioral tasks. Arc expression regulates the persistent firing of individual neurons and predicts the consolidation of neuronal ensembles during repeated learning. Therefore, the Arc pathway represents a prototypical example of activity-dependent genetic feedback regulation of neuronal ensembles. The activation of this pathway in the frontal cortex starts during early postnatal development and requires dopaminergic input. Conversely, genetic disruption of Arc leads to a hypoactive mesofrontal dopamine circuit and its related cognitive deficit. This mutual interaction suggests an auto-regulatory mechanism to amplify the impact of neuromodulators and activity-regulated genes during postnatal development. Such a mechanism may contribute to the association of mutations in dopamine and Arc pathways with neurodevelopmental psychiatric disorders. As the mesofrontal dopamine circuit shows extensive activity-dependent developmental plasticity, activity-guided modulation of dopaminergic projections or Arc ensembles during development may help to repair circuit deficits related to neuropsychiatric disorders. |
| Databáze: | OpenAIRE |
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