Genetic and environmental factors interact for the determination of phenotype, both normal and pathological. Despite this fact, in most cases, animal models of diseases employ only genetic interventions (Crispr technology, knock-out or transgenes) to address the etiopathogenesis of human conditions with documented genetic bases, which account to a small percent of all human diseases. Few animal disease models employ environmental manipulations, mostly to simulate psychiatric conditions. In these models, negative early experiences have been used, usually in the form of disruption of mother-offspring interactions, to investigate the underlying mechanisms of conditions such as depression, anxiety and prefrontal cortex-dependent deficits. In the present study an early experience of mild adversity, which has been documented to model child neglect, will be employed to investigate prefrontal cortex development and function in the rat.

WP2 Role of dopamine in neuronal proliferation and differentiation during the early postnatal development
The DER experience-induced dopamine depletion, prohibited the normal maturation of dividing cells in the lateral ventricles of the brain, halting dividing cells in early stages of differentiation, and eventually leading them to apoptosis.

WP3 Role of dopamine in neuronal migration during the early postnatal development
Depletion of dopamine due to the DER experience possibly induces aberrant migration trajectory, resulting in reduced number of neurons in the medial orbital prefrontal cortex. 

WP5 Short- and long-term effects of glial activation during the early postnatal development
The DER-induced effects on astrocytes and neurons in the ventro-medial part of the PND13 prefrontal cortex are not dependent on the DER-induced microglia activation.

WP7 Type of dopamine receptors responsible for the effects of PFC dopamine depletion on micro- and astroglia
Depletion of dopamine due to the DER experience  induces micro- and astroglia activation in PND13 medial orbital prefrontal cortex. This phenomenon is prevented by activation of D2-like receptors.
aberrant migration trajectory, resulting in reduced number of neurons in the medial orbital prefrontal cortex.