Figure 1. Postnatal development of dopamine and glutamatergic transmission in the PFC.

(A) D1 receptor modulation of NMDA transmission in deep-layer pyramidal neurons increases after P45 to reach steady state, adult level by around P60 (Tseng and O’Donnell 2005; Flores-Barrera et al., 2014). A similar pattern of dopamine (DA) innervation was observed in the PFC. Dopaminergic fibers can be found in deep layers soon after birth, yet the density of DA innervation in the prelimbic cortex continues to increase until P60 (Kalsbeek et al, 1988). Similarly, DA modulation of GABAergic activity in the PFC undergoes developmental regulation such that D1 and D2 receptor-mediated facilitation of interneuronal excitability becomes markedly enhanced after P50 (Tseng and O’Donnell 2007). (B) GluN2B-NMDA receptor transmission begins to emerge in the apical dendrite of layer V pyramidal neurons in the PFC around P45 (Flores-Barrera et al., 2014). This developmental change is required to strengthening PFC processing of ventral hippocampal inputs (Flores-Barrera et al., 2014) and to enable the increased D1 receptor modulation of NMDA-mediated responses described in A. (C) PFC processing of ventral hippocampal drive is also developmentally regulated as revealed by the mechanisms contributing to the induction of prefrontal LTP and LTD following high-frequency stimulation of the ventral hippocampus (Caballero et al., 2014; Flores-Barrera et al., 2014). While prefrontal LTP is dependent on local GluN2B-NMDA transmission, D1 receptor (D1R) activation and protein-kinase A (PKA) signaling, prefrontal LTD relies on the recruitment of local GABAergic interneurons and GABA-A receptor (GABA_AR)-mediated transmission.