A-Current Expression is Regulated by Activity but not by Target Tissues in Developing Lumbar Motoneurons of the Chick Embryo

Abstract

Casavant, Reema H., Costa M. Colbert, and Stuart E. Dryer. A-current expression is regulated by activity but not by target tissues in developing lumbar motoneurons of the chick embryo. J Neurophysiol 92: 2644 -2651, 2004. First published May 26, 2004 10.1152/ jn.00307.2004. The functional expression of A-type K ϩ channels (I A ) was examined in chick lumbar motoneurons (LMNs) at embryonic days 6 and 11 (E6 and E11). We observed a threefold increase in I A density between E6 and E11 in spinal cord slices and acutely dissociated LMNs. There was no change in current density, kinetics, or voltage dependence of I A in E11 homozygous limbless mutants or in E11 embryos in which hindlimbs were surgically removed at E6. Moreover, chronic in ovo administration of D-tubocurarine, which causes an increase in motoneuron branching on the surface of target muscles, had no effect on I A . Electrical activity played an important role in I A regulation in LMNs in vitro and in ovo. Blocking spontaneous electrical activity of LMNs by chronic in ovo application of mecamylamine or muscimol reduced I A by 80%. LMNs cultured in the presence of TTX also failed to express normal densities of I A , even when the cultures also contained target tissues. The portion of I A that remained after in ovo or in vitro blockade of activity inactivated more quickly than the I A of LMNs that were allowed to discharge spikes. The developmental expression of LMN I A increases significantly during development, and this increase is activity dependent but does not require interactions with target tissues. Ongoing activity also seems to regulate the kinetics of I A inactivation. I N T R O D U C T I O NNeuronal populations can be distinguished by their morphological, physiological, and biochemical characteristics. The intrinsic electrophysiological properties of neurons represent an especially important phenotypic trait, because they control the resting level of excitability, the transmission of impulses, and the integration of synaptic inputs. These intrinsic properties are determined by the functional expression of a specific ensemble of ionic channels.The mature complement of neuronal ion channels is not present at the stage of terminal mitosis. Rather, channel expression is a dynamic and developmentally regulated process. The developmental expression of some types of channels proceeds according to an internal developmental program (Dourado and Dryer 1992; Spitzer and Lamborghini 1976), whereas expression of others appears to require neurotrophic interactions with other cell types, ongoing electrical activity, or both (reviewed in Dryer et al. 2003). Although the precise spatiotemporal pattern of channel expression depends on the cell population being studied, the developmental expression of some channels, including Ca 2ϩ -activated K ϩ channels (I K(Ca) ) and A-type K ϩ channels (I A ), requires cell-cell interactions in several neuronal populations (Cameron et al. , 1999(Cameron et al. , 2001 Dryer 1992, 1994;Dourado et al. 1994; Martin-Caraballo and ...

Compensatory changes in cellular excitability, not synaptic scaling, contribute to homeostatic recovery of embryonic network activity

“…Previous studies of vertebrate central synapses have shown homeostatic increases in sodium channel currents (8,20), reductions in Ca 2ϩ -activated potassium currents (16,20), and reductions in the density and inactivation kinetics of transient potassium channels (14) after TTX-induced activity block. We have blocked GABA A transmission and see comparable results to these previous studies that block activity, suggesting a similar process has been triggered.…”

“…SNA is produced by hyperexcitable, recurrently connected circuits in which both GABA and glutamate are excitatory. In the developing spinal cord, SNA has been shown to be important for various aspects of limb (13) and motoneuron (14)(15)(16) development. We have shown recently that when SNA was reduced for 48 h in vivo, compensatory increases in AMPA and GABA A quantal amplitude were triggered, suggesting that homeostatic synaptic plasticity contributed to the maintenance of SNA (9).…”

Homeostatic synaptic plasticity in developing spinal networks driven by excitatory GABAergic currents

“…Homeostatic changes in intrinsic cellular excitability following reductions in spiking activity have been observed for many years and likely play a significant role in recovering or maintaining network activity levels following perturbations (Turrigiano et al, 1994; Thoby-Brisson and Simmers, 1998; Desai et al, 1999; Marder and Prinz, 2002; Karmarkar and Buonomano, 2006; Marder and Goaillard, 2006; Khorkova and Golowasch, 2007) including the chick embryo (Martin-Caraballo and Dryer, 2002; Casavant et al, 2004). Several different channels appear to contribute to the compensatory changes in cellular excitability including transient and calcium-activated potassium channels (I A and I K(Ca) , respectively), the hyperpolarization activated cationic conductance (I H ), and voltage gated sodium channels (I Na ).…”

Pharmacological manipulation of GABA-driven activity in ovo disrupts the development of dendritic morphology but not the maturation of spinal cord network activity

“…For example, inhibition of GABAergic neurotransmission prevents motor axonal guidance [11]. Similarly, GABA-driven network activity regulates the electrical differentiation of spinal motoneurons, including Ca 2+ -dependent and A-type K + channel expression [12,13]. Little is known regarding the role of GABA-mediated activity in regulating the morphological maturation of spinal neurons.…”