DARPP‐32, a phosphoprotein enriched in dopaminoceptive neurons bearing dopamine D1 receptors: DIstribution in the cerebral cortex of the newborn and adult rhesus monkey

Abstract

DARPP‐32, a dopamine (DA) and cAMP‐regulated phosphoprotein, is associated with dopaminoceptive neurons bearing D‐1 receptors in the basal ganglia. The present study addressed the distribution of DARPP‐32 in the primate cerebral cortex and its putative association with D‐1 receptor laden cells in this structure. DARPP‐32‐like immunoreactive (LIR) neurons were examined in the cerebral cortex of 3‐day‐old (P3), 6‐week‐old (P42), and adult rhesus monkeys. In the younger cases, a large number of DARPP‐32 positive neurons, with the morphological characteristics of pyramidal cells, were observed throughout the cortex, in layers V–VI, and to a lesser extent in layer II and uppermost layer III. In the parietal, insular, temporal, and occipital cortices, DARPP‐32 positive neurons were arranged in a monolayer in layer Va. They were often clustered in small groups with a bundling of their dendrites. In the primary motor cortex, Betz cells were among the labeled population. In the association and somatosensory areas, the basal dendrites of DARPP‐32 positive neurons and the prominent tufting of their apical dendrites in layer I contributed to an essential bilaminar pattern resembling the distribution reported for DA afferents and D‐1 receptors in these areas. The prominence and widespread distribution of DARPP‐32 positive neurons in layer V may be a specialization of primate cortex since such cells are found only in restricted locations in rodents. The literature on the connections of the cerebral cortex suggests that a large number of the DARPP‐32 positive neurons in layer VI and perhaps even in layer Va may be corticothalamic neurons. An important developmental observation was the presence of DARPP‐32‐LIR neurons in the white matter. They were prominent in the neonates but could not be seen in the adult. Their location as well as their type and shape were reminiscent of interstitial neurons. In the adult monkeys, the distribution of DARPP‐32‐LIR neurons was more circumscribed: they were numerous in the ventral temporal gyrus and in areas related to the limbic system: caudal orbitofrontal cortex, insula, temporal pole, entorhinal, and anterior cingulate cortex. Weak labeling was detected in layer Va of the superior temporal and parietal cortex, in some prefrontal areas (10,13, and medial 9), and in the premotor and supplementary motor cortex; in adults, unlike neonates, few DARPP‐32‐LIR neurons were present in the dorsolateral prefrontal cortex, the primary motor or the primary visual or prestriate cortices. These findings demonstrate important developmental changes between birth and adulthood in the expression of DARPP‐32 and point to a possible role for this molecule and/or D‐1 receptors during postnatal development of the primate cerebral cortex.