Laminar development of the mouse barrel cortex: effects of neurotoxins against monoamines

Abstract

The rodent somatosensory cortex is characterized by a unique cellular organization in the field of representation of the whiskers, called the barrelfield, which develops in layer IV during the 1st postnatal week in parallel with the establishment of the thalamo-cortical connections. This area is transiently densely innervated by serotonergic afferents during this period. Serotonin depletion delays the formation of barrels in the rat somatosensory cortex. However, no information is available to date on the time-course of the laminar differentiation of the cortex after monoaminergic depletion and the relative contribution of different monoaminergic inputs to this process. To address these issues, newborn mice were treated with selective neurotoxins (6-hydroxydopamine or 5,7-dihydroxytryptamine) at birth to destroy the catecholaminergic and monoaminergic cortical innervation, respectively. The parietal cortex of these animals was examined in Nissl-stained coronal sections prepared on different days of postnatal development (between P2 and P30). Compared with the controls, delayed growth and differentiation of the cortical layers II-IV were observed in the treated animals, most prominently between P2 and P16. From the 3rd postnatal week, no cytoarchitectonic difference could be detected. Although neonatal depletion of the cortical monoaminergic innervation does not affect the laminar organization of the adult mouse barrelfield, it significantly delays the time-course of development of several cortical layers. This delay generates a mismatch in the degree of maturation between cortical neurons and their afferents at a time when neuronal interactions are critical for the establishment of local circuitry.

Early Pharmacological Treatment of Autism: A Rationale for Developmental Treatment

“…However, too much serotonin results in immature, widely dispersed dendritic branches (Mooney et al 1994;Salichon et al 2001). Too little serotonin results in fewer dendritic spines, abnormally small dendritic arbors and somatosensory barrels, and reduced synaptic density (Bennett-Clarke et al 1994;Mazer et al 1997;Osterheld-Haas and Hornung 1996;Yan et al 1997). This finding is consistent with the observation that minicolumns in individuals with autism are narrower than those of individuals with typical development (Casanova et al 2002b).…”

Postnatal Growth Defects in Mice with Constitutive Depletion of Central Serotonin

“…These observations are consistent with previous observations of a delayed laminar differentiation after lesions of the 5-HT pathways in neonatal rats. 9 While it is difficult to disentangle a direct effect of 5-HT depletion on cortical growth from an indirect one, secondary to general growth retardation, the temporal course of both events suggests that they could be independently regulated. Indeed, overall hemispheric and cortical size normalized by P30, an age where there was still a significant growth retardation.…”

Neonatal serotonin depletion alters behavioral responses to spatial change and novelty

“…In cerebral cortical development, early manipulations of the serotonergic innervation lead to altered development and plasticity in sensory areas in a variety of species (Gu and Singer, 1995;Osterheld-Haas and Hornung, 1996;Janusonis et al, 2004). In rat, neonatal systemic depletion of the cortical serotonergic innervation delays thalamocortical patterning (Blue et al, 1991) and diminishes the size of the barrel field area during the first postnatal week (Bennett-Clarke et al, 1994).…”