The Impact of the Mesoprefrontal System on the Development of the Prefrontal Cortex

Khondker Ushna Sameen Islam1, Kayeon Jung1, Antonia-Antigoni Sinani1, Heinz Beck2, Dirk Isbrandt3, Sandra Blaess1

1 Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany
2 Laboratory of Experimental Epileptology and Cognition Research, Department of Epileptology, University of Bonn
3 Institute for Molecular and Behavioral Neuroscience, University of Cologne ; Experimental Neurophysiology, German Center for Neurodegenerative Diseases, Bonn

The prefrontal cortex (PFC) is implicated in important cognitive processes and undergoes a protracted functional and anatomical remodeling during the neonatal and adolescence phase. Altered maturation of PFC microcircuits and inputs might contribute to susceptibility to mental illnesses such as schizophrenia, which usually first manifest themselves during adolescence and are associated with PFC-dependent cognitive impairments.

Midbrain dopaminergic (DA) neurons of the ventral tegmental area (VTA) project to the PFC and modulate activity of interneurons and pyramidal neurons. They regulate the cognitive and emotional functions processed by the PFC together with other monoaminergic neuromodulators, noradrenaline and serotonin. A subpopulation of these PFC-projecting DA neurons can co-release glutamate (Glut-DA neurons) and there are also non-DA Glut VTA neurons targeting the PFC. Together they form the mesoprefrontal system. The DA component of the mesoprefrontal system matures postnatally up until early adulthood correlating with maturation of PFC interneurons and local microcircuits. Given this extensive postnatal development, mesoprefrontal inputs could play an important role in the maturation of PFC microcircuits. To examine how alterations in the mesoprefrontal pathway affect the development of local PFC microcircuits, we are using a mouse model that lacks DA innervation into the PFC. We find that in absence of DA projections, parvalbumin, expressed by fast-spiking interneurons, is reduced, while the number of calbindin expressing interneurons is increased. We are also investigating how dopamine receptor expression changes in the PFC in our mouse model and if there is potential compensation by other neuromodulators in absence of dopamine.