Postnatal development of the tyrosine hydroxylase-containing cell population within the rat locus coeruleus: topological organization andphenotypic plasticity

Abstract

The cellular phenotypic characteristics of tyrosine hydroxylase (TH) expression have been studied within the rat locus coeruleus (LC) during postnatal development at six different stages: postnatal day 4 (PND4), PND10, PND14, PND21, PND30, and PND42. Coronal brain sections were selected at intervals of 80 microns along the caudorostral extent of the LC and processed for TH immunohistochemistry. At each anatomical level we (1) reconstructed the mean space of the LC delineated by the TH positive cell bodies, (2) enumerated the mean number of these cell bodies, and (3) determined the mean volume circumscribed by these cell bodies and their density. The topological study revealed a steady remodeling of the structure until the third week, with a progressive reducing of a ventral cellular group in the anterior LC, which was no longer observable at PND21, concomitant to the stretch of the structure toward its caudal limit. We have noted invariant and variant cellular phenotypic characteristics of TH expression. At any stage, the LC could be separated into a posterior and an anterior subregion and its total volume remained quite stable during the studied period. At PND14 and PND21, we observed a transient 33% increase in the total number of TH positive perikarya as compared to PND42. Conjoint analysis of the topological reconstruction and the density of TH positive cells suggested there were three distinct and precisely localized subsets of "quiescent" neurons. TH gene expression in these cells would have lowered between PND14 and PND21 inside two subsets and between PND21 and PND30 inside the last one. So topologically defined populations of cells could be involved in specific functions. If they have not definitively lost their TH expression capacity, they could contribute to increasing TH levels in LC occurring in response to physiological perturbations or pharmacological treatments.

Early undernutrition decreases the number of neurons in the locus coeruleus of rats

“…These findings, together with our previous study, might suggest that the lack of effect of undernutrition on the number of neurons at P12 is associated with the maximal organizational period in the LC, which occurs in the second week and may compensate for the effects of undernutrition. In addition, the second week of postnatal life is a crucial period for the development of several morphological and neurochemical characteristics of the LC, including the tyrosine hydroxylase (TH) content of the cell (Zyzek et al 1990;Benzin et al 1994;Rousset et al 1994;Benzin et al 1997;Benzin et al 2000), reorganization of cellular bodies (Sisk and Foster 2004) and number of TH positive cells in the LC, which reaches a maximum by day P14 (Benzin et al 1994). An important question arising from these results concerns whether the number of LC neurons can be recovered to control values if nutritional rehabilitation starts at earlier stages of development.…”

Delayed plasticity of the mesolimbic dopamine system following neonatal 6-OHDA lesions

“…Alternatively, an actual increase in the number of neurons expressing TH mRNA could occur as has been proposed for conditions and brain regions (Bezin et al, 1994;Iacovitti et al, 1987;Tashiro et al, 1989;Weiser et al, 1993), for example, by blockade of a normal pruning of TH-expressing neurons during development (Kedzierski and Porter, 1990). A closer examination of the TH mRNA-expressing neurons at the cellular level is currently being undertaken to address these issues directly.…”

Role of A5 noradrenergic neurons in the chemoreflex control of respiratory and sympathetic activities in unanesthetized conditions

“…During development, an increase in the tyrosine-hydroxylase activity in pontine-medullary neurons is an important step for the maturation of respiratory system (Bezin et al, 1994; Lagercrantz et al, 1994). In adults, lesions of the brainstem catecholaminergic neurons reduce resting arterial pressure and breathing frequency, impair hypoxia-induced sympathoexcitatory response and depress the ventilatory response to hypercapnia (Schreihofer and Guyenet, 2000; Li and Nattie, 2006).…”