Maturation of rhythmic neural network: role of central modulatory inputs Val  erie F enelon a , Yves Le Feuvre a , Tiaza Bem b , Pierre Meyrand a, * a Laboratoire de Neurobiologie des R eseaux, UMR 5816 Universit e Bordeaux I CNRS, 1, Avenue des Facultes, 33405 Talence, France b Institute of Biocybernetics and Biomedical Engineering, PAS, Warsaw 02-109, Poland Abstract Modulatory systems are well known for their roles in tuning the cellular and synaptic properties in the adult neuronal networks, and play a major role in the control of the flexibility of functional outputs. However far less is known concerning their role in the maturation of neural networks during the development. In this review, using the stomatogastric nervous system of lobster, we will show that the neuromodulatory system exerts a powerful influence on developing neural networks. In the adult the number of both motor target neurons and their modulatory neurons is restricted to tens of identifiable cells. They are therefore well characterized in terms of cellular, synaptic and morphological properties. In the embryo, these target cells and their neuromodulatory population are already present from mid-embryonic life. However, the motor output generated by the system is quite different: while in the embryo all the target neurons are organized into a single network generating unique motor pattern, in the adult this population splits into two distinct networks generating separate patterns. This ontogenetic partitioning does not rely on progressive acquisition of adult properties but rather on a switch between two possible network operations. Indeed, adult networks are present early in the embryonic life but their expression is repressed by central modulatory neurons. Moreover, embryonic networks can be revealed in the adult system again by altering modulatory influences. Therefore, independently of the developmental age, two potential network phenotypes co-exist within the same neuronal architecture: when one is expressed, the other one is hidden and vice versa. These transitions do not necessarily need dramatic changes such as growth/retraction of processes, acquisition of new intra-membrane proteins etc. but rather, as shown by modelling studies, it may simply rely on a subtle tuning of pre-existing intercellular electrical coupling. This in turn suggests that progressive ontogenetic alteration may not take place at the level of the target network but rather at the level of modulatory input neurons. Ó 2003 Elsevier Ltd. All rights reserved. Keywords: Stomatogastric nervous system; Development; Neural network; Neuromodulation 1. Introduction The development of the brain and the elaboration of functional neural networks require two main and sequential phases. The early one consists in a compar- timentalization and elaboration of future functional boundaries within the brain in development [20]. After this early brain patterning which leads to the segregation of sub-populations of neurones organized in proto-net- works that display spontaneous activities, these proto- networks undergo maturation. This latter phase involves a lot of mechanisms which are not exclusive but even can act in conjunction. They include activity-dependent mechanisms [9,15], variations of hormonal environ- ment [8] and changes in neuromodulatory systems [18,23]. In this review we will only deal with the maturation phase and mainly with the role of neuromodulation. The current view is that as modulatory inputs reach their target networks they tune network’s cellular and syn- aptic properties and therefore lead to a mature system [32]. However, using the stomatogastric nervous system (STNS) of crustaceans, we were able to demonstrate that neuromodulatory inputs may play a completely different role since they are able to repress the expression of adult like networks in the embryo [18]. In this con- text, instead of a progressive maturation of neural net- works during the course of development, these networks which are present earlier than expected in their adult * Corresponding author. Tel.: +33-5-5796-2562; fax: +33-5-5796- 2561. E-mail address: p.meyrand@lnr.u-bordeaux.fr (P. Meyrand). 0928-4257/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.jphysparis.2003.10.007 Journal of Physiology - Paris 97 (2003) 59–68 www.elsevier.com/locate/jphysparis