Exp Brain Res (1989) 78:279 289 Experimental BrainResearch 9 Springer-Verlag1989 Morphometric analysis of prefrontal cortical development following neonatal lesioning of the dopaminergic mesocortical projection A. Kalsbeek, M.A.H. Matthijsscn, and H.B.M. Uylings Netherlands Institute for Brain Research, Meibergdreef 33, NL-1105 AZ Amsterdam, The Netherlands Summary. In this study the possibility that dopa- mine (DA) plays a trophic role in cortical develop- ment was studied by analysing cortical morphology and dendritic arborization of pyramidal cells after neonatal depletion of DA. The prefrontal cortex (PFC) was depleted of a DA innervation from postnatal day 1 onwards by thermal lesions of the DA cell group (A10) in the ventral tegmental area. Measurements of the cortical thickness and volume of the PFC subareas did not reveal any gross altera- tions. The DA-depleted animals, however, showed a 30% decrease in the total length of the basal dendrites of the pyramidal cells in layer V of the medial PFC. These cells constitute the primary target of the dopaminergic innervation in the pre- frontal cortex. The decreased dendritic length was due mainly to a reduced branching frequency of the basal dendrites. The present results of the dendritic measurements support a trophic role for DA in neuronal differentiation. Key words" Golgi-study - Dendrite - Pyramidal cell - Cortical thickness - Volumetry - Immunocy- tochemistry - Regression - Rats Introduction The major catecholaminergic cell groups are formed and undergo differentiation during early stages of development (Tennyson et al. 1973; Lauder and Bloom 1974). In rats these axons reach the subplate of the neocortex approximately 1 week before birth (Kalsbeek et al. 1988a), at a stage of development when other types of neurones - in- cluding the ones that will eventually be their target cells are either unformed or not fully differen- tiated. At birth the synaptic structures of the rat O~))rint requests to. A. Kalsbeek (address see above) neocortex are mainly monoaminergic terminals (Coyle and Molliver 1977), which suggests that monoamine neurones play an important on- togenetic or developmental role in the cerebral cor- tex, prior to the actual onset of neurotransmission (Lauder and Bloom 1974; Buznikow 1984; Matt- son 1988). There are, however, some marked differences between the full-grown cortical innervation pat- terns of the three monoamines. Noradrenaline and serotonin have a widespread, rather homogeneous innervation pattern, whereas dopamine has a more "focused" innervation pattern (Morrison and Magistretti 1983; Parnavelas and McDonald 1983). In rodents, the prefrontal cortex (PFC) is virtually the only neocortical area, besides the en- torhinal cortex, with a dense and extensive dopami- nergic innervation (Van Eden et al. 1987; Doucet et al. 1988). Removal of the mesocortical dopaminergic fi- bres shortly after birth has previously been shown to cause both behavioural deficits (Kalsbeek et al. 1988b, 1989a) and a reduction in the cortical thick- ness of the medial part of the PFC (Kalsbeek et al. 1987). The exact mechanisms that underlie the re- duction in cortical thickness are not clear, as the cortical thickness may reflect both the number of cells and the size of their tree structures. The goal of the present study was to examine further the effects of perinatal depletion of the DA innervation in the PFC. In addition to a more comprehensive measurement of cortical thickness, volumetric quantifications were performed in the different PFC subareas. Dendritic arbors of pyra- midal cells were examined as a possible point of impact of the mechanisms underlying the reduction in cortical size. Measurements were focused on the pyramidal cells in layer V, as this layer contains the highest density of dopaminergic fibres and the