Relationship between GABAergic interneurons migration and early neocortical network activity

Abstract

Available evidence converges to suggest that during the early development of the cerebral cortex, the emergence of the spontaneous network activity chronologically overlap with the end of the cell migration period in the developing cortex. We approached the functional regulation of neuronal migration in a culture model of neocortical networks, using time lapses to detect migratory movements, calcium-imaging to assess the activity of migratory neurons, and immunocytochemical methods to identify the migratory cells retrospectively. In cell cultures, early physiological development and cell migration are reproduced at a local network level, thus allowing the study of the interrelationships between cell migration and network development independent of the topographical complexity. Neurons migrate at least until 12 days in vitro and GABAergic neurons migrate faster compared with non-GABAergic neurons. A decline of migratory activity was coincident with the development of spontaneous synchronous network activity. Migrating interneurons did not participate in synchronous network activity, but interneurons that ended cell migration during observation time frequently engaged in synchronous activity within less than an hour. Application of GABA(A) and ionotropic glutamate receptor antagonists significantly increased the number of migrating GABAergic neurons without changing the dynamics of the migratory movements. Thus, neurotransmitters released by early network activity might favor the termination of neuronal migration. These results reinforce the idea that network activity plays an important role in the development of late-born GABAergic cells.

Orchestration of "presto" and "largo" synchrony in up-down activity of cortical networks

“…We showed how the total NN in each examined culture was rather homogeneous and that GABA positive neurons ranged between 11.8 and 25.2% of the neuronal population with a mean of 19. 2 ± 1.4% (SEM, n = 9), a value consistent with previous reports on interneuronal cortical population both in vitro and in vivo (Gabbott et al, 1997; Sang and Tan, 2003; Tsugorka et al, 2007; de Lima et al, 2009). From experiments/animals E2 and E4 two cultures were labelled by MAP2/GABA immunofluorescence giving similar results (15.4 ± 6.8% SD and 25.5 ± 6% SD respectively), demonstrating the reproducibility of the methods.…”

“…Only recently this species has been used for such analysis, because of the increasing number of studies on experimental transgenic models of human neuropathologies. However, numerous papers on cultured cortical neurons both from mice (Lesuisse and Martin, 2002; Sang and Tan, 2003; Klueva et al, 2008) and from rats (de Lima and Voigt, 1997; de Lima et al, 2004, 2007, 2009; Kato-Negishi et al, 2004; Magnusson et al, 2008) used embryonic cultures. In fact, postnatal cultures are more difficult to obtain, but the networks are functioning and mature after the first week in vitro (Gullo et al, 2009).…”

A framework for modeling the growth and development of neurons and networks

“…Alternatively, modules could implement an interface for online communication with a coexisting electrophysiology simulator. This feature would of course be of great interest, because of the direct influence of electrical activity on neurite outgrowth (Hutchins and Kalil, 2008), or on interneuron migration (de Lima et al, 2009); and in a later phase to study phenomena like synaptic competition (Turrigiano, 2008) and learning (Butz et al, 2009). A further limitation of the present version of CX3D is that it runs on a single processor, so limiting both the speed and the size of simulations.…”

GABAergic Signaling Increases Through the Postnatal Development to Provide the Potent Inhibitory Capability for the Maturing Demands of the Prefrontal Cortex

“…Electrical activities of pyramidal neurons play important roles in developmental processes of LTS interneurons including neuronal differentiation, migration, and maturation. This is in line with that the neuronal activities of early differentiating neurons might influence the behavior of late-born migrating neurons (de Lima et al 2009;Pla et al 2006;Nakajima 2007). It may also be speculated that the defects of excitability of pyramidal cells owing to the barren circumstance and poor experiences must be able to result in dysfunction of interneurons with migration or maturation.…”