Dysregulation of the mesoprefrontal dopamine circuit mediates an early-life stress-induced synaptic imbalance in the prefrontal cortex
| Autor: | M. McLean Bolton, Douglas Asede, Gabriela Garrido Rodriguez, Kanghoon Jung, Won Chan Oh, Roberto Ogelman, In Wook Hwang, Hyung Bae Kwon |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
PFC
Male 0301 basic medicine QH301-705.5 Dopamine Prefrontal Cortex excitatory synapse Biology Inhibitory postsynaptic potential Article General Biochemistry Genetics and Molecular Biology inhibitory synapse Mice 03 medical and health sciences 0302 clinical medicine Excitatory synapse Dopamine receptor D2 medicine Animals Biology (General) Prefrontal cortex Ventral tegmental area 030104 developmental biology medicine.anatomical_structure Synaptic plasticity Excitatory postsynaptic potential early-life stress Neuroscience VTA 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Cell Rep Cell Reports, Vol 35, Iss 5, Pp 109074-(2021) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2021.109074 |
| Popis: | Summary Stress adversely affects an array of cognitive functions. Although stress-related disorders are often addressed in adulthood, far less is known about how early-life stress (ELS) affects the developing brain in early postnatal periods. Here we show that ELS, induced by maternal separation, leads to synaptic alteration of layer 2/3 pyramidal neurons in the prefrontal cortex (PFC) of mice. We find that layer 2/3 neurons show increased excitatory synapse numbers following ELS and that this is accompanied by hyperexcitability of PFC-projecting dopamine (DA) neurons in the ventral tegmental area. Notably, excitatory synaptic change requires local signaling through DA D2 receptors. In vivo pharmacological treatment with a D2 receptor agonist in the PFC of control mice mimics the effects of ELS on synaptic alterations. Our findings reveal a neuromodulatory mechanism underlying ELS-induced PFC dysfunction, and this mechanism may facilitate a more comprehensive understanding of how ELS leads to mental disorders. |
| Databáze: | OpenAIRE |
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