Neural Circuits and Systems Neuroscience
Author: Tamara Sol Adjimann | email: tamara.adjimann@gmail.com
Tamara S. Adjimann 1°, Sebastian P. Fernandez 2°, Jacques Barik 2°, Mariano Soiza-Reilly 1° 1°
1° Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) Universidad de Buenos Aires, Argentina.
2° Université Côte d’Azur, Nice, France; Institut de Pharmacologie Moléculaire & Cellulaire, CNRS UMR7275, Valbonne, France.
The prefrontal cortex to dorsal raphe nucleus (PFC-DRN) circuit is crucially engaged in stress-coping and emotional behaviors. Mice exposed to the selective serotonin reuptake inhibitor (SSRI) fluoxetine from P2 to P14 (PN-FLX) show alterations in the connectivity of the PFC-DRN circuit, accompanied by increases in depressive-like and anxiety behaviors in adult life. To investigate the early impact of PN-FLX on the developing PFC-DRN circuit, we combined the use of high-resolution synaptic anatomy (array tomography) and ex-vivo electrophysiology. As early as at P15, a selective 40% increase in the density of prefrontal glutamate synaptic afferents was found in the DRN of PN-FLX mice in comparison to controls. Consistently, an increased frequency of excitatory postsynaptic currents was also detected on DRN serotonin neurons indicating the presence of more functional glutamate synapses. Next, we evaluated the activation of PFC projection-neurons engaged in the PFC-DRN circuit in response to an acute stress (forced swim). Using layer-specific markers and c-fos immunohistochemistry, we determined that PN-FLX differentially enhanced the activity of subsets of PFC projection-neurons. Our results show multiple early effects of PN-FLX on the developing PFC-DRN circuitry that could contribute to long-term emotional alterations.