Accommodation of mouse DRG growth cones to electrically induced collapse: kinetic analysis of calcium transients and set-point theory.

Electrical stimulation causes growth cones of mouse dorsal root ganglion neurons to collapse. During chronic stimulation, however, growth cones resume motility. In addition, these growth cones are now resistant to the collapsing effects of subsequent stimulation, a process we term accommodation. We compared the kinetics of electrically induced Ca2+ transients in naive and accommodated growth cones in order to determine whether the accommodation process results from a change in the Ca2+ transient, or a change in the Ca2+ sensitivity of the growth cones. Three kinetics were determined: (1) the initial increase to peak Ca2+ levels produced by 10 Hz stimulation; (2) recovery from peak Ca2+ levels during stimulus trains lasting 15 min; and (3) clearing of Ca2+ from growth cones after terminating the stimulus. These kinetics were analyzed using single exponential fits to changes in fura-2 fluorescence ratios. The electrically evoked increase in Ca2+ was significantly slower in accommodated growth cones (tau = 6.0 s) compared to naive growth cones (tau = 1.4 s). Despite the slower increase of [Ca2+]i in accommodated growth cones, peak [Ca2+]i was similar to that reached in naive growth cones, and the steady-state Ca2+ level was significantly elevated after chronic stimulation. Thus, accommodated growth cones maintained outgrowth at [Ca2+]i that caused collapse initially. Time course experiments show that accommodation is a slow process (t 1/2 = about 3 h). Accommodation did not induce measurable changes in the rates of Ca2+ homeostasis during or after stimulus trains. The kinetics of Ca2+ recovery during (tau = 90 s) and after 15 min of stimulation (tau = 8.5 s) was not significantly different in accommodated versus naive growth cones. Rates of 45Ca2+ efflux were also similar in both types of growth cones. These results suggest two regulatory processes contributing to growth cone motility during chronic stimulation: (1) recovery of [Ca2+]i to levels permissive to neurite outgrowth, and (2) an increase in the range of optimal [Ca2+]i for growth cone motility. These adaptive responses of mammalian growth cones to chronic stimulation could be involved in the modulation of CNS development by electrical activity of neurons.

[1]  S. Bolsover,et al.  A narrow window of intracellular calcium concentration is optimal for neurite outgrowth in rat sensory neurones. , 1992, Brain research. Developmental brain research.

[2]  WG Regehr,et al.  Electrical activity increases growth cone calcium but fails to inhibit neurite outgrowth from rat sympathetic neurons , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  A. Dolphin,et al.  Aspects of vertebrate neuronal voltage-activated calcium currents and their regulation , 1991, Progress in Neurobiology.

[4]  Richard J. Miller.  The control of neuronal Ca2+ homeostasis , 1991, Progress in Neurobiology.

[5]  W. Lederer,et al.  Photorelease of Ca2+ Produces Na‐Ca Exchange Currents and Na‐Ca Exchange “Gating” Currents a , 1991, Annals of the New York Academy of Sciences.

[6]  T. Allen.  The Exchange in Intact Squid Axonsa a , 1991 .

[7]  J. Connor,et al.  Dendritic spines as individual neuronal compartments for synaptic Ca2+ responses , 1991, Nature.

[8]  S. B. Kater,et al.  Independent regulation of calcium revealed by imaging dendritic spines , 1991, Nature.

[9]  S. Kater,et al.  Regulation of growth cone behavior by calcium , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  P G Nelson,et al.  Calcium, network activity, and the role of NMDA channels in synaptic plasticity in vitro , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  P G Nelson,et al.  Effects of patterned electrical activity on neurite outgrowth from mouse sensory neurons , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  F S Fay,et al.  Ca2+ imaging in single living cells: theoretical and practical issues. , 1990, Cell calcium.

[13]  F S Fay,et al.  Intracellular calibration of the fluorescent calcium indicator Fura-2. , 1990, Cell calcium.

[14]  R. Campenot,et al.  Growth of sympathetic nerve fibers in culture does not require extracellular calcium , 1989, Neuron.

[15]  P G Nelson,et al.  Synaptic connections in vitro: modulation of number and efficacy by electrical activity. , 1989, Science.

[16]  S. B. Kater,et al.  Calcium regulation of the neuronal growth cone , 1988, Trends in Neurosciences.

[17]  D. Tank,et al.  Spatially resolved calcium dynamics of mammalian Purkinje cells in cerebellar slice. , 1988, Science.

[18]  Samuel Thayer,et al.  Regulation of calcium homeostasis in sensory neurons by bradykinin , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  S. B. Kater,et al.  Components of neurite outgrowth that determine neuronal cytoarchitecture: Influence of calcium and the growth substrate , 1988, Journal of neuroscience research.

[20]  M. Mattson,et al.  Calcium regulation of neurite elongation and growth cone motility , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  S. Kater,et al.  Electrically and chemically mediated increases in intracellular calcium in neuronal growth cones , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  R. Balázs,et al.  The role of depolarization in the survival and differentiation of cerebellar granule cells in culture , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  C. Heizmann,et al.  Expression of parvalbumin and other Ca2+-binding proteins in normal and tumor cells: a topical review. , 1987, Cell calcium.

[24]  S. B. Kater,et al.  Suppression of neurite elongation and growth cone motility by electrical activity. , 1986, Science.

[25]  R Y Tsien,et al.  Measurement of cytosolic free Ca2+ in individual small cells using fluorescence microscopy with dual excitation wavelengths. , 1985, Cell calcium.

[26]  R. Tsien,et al.  A new generation of Ca2+ indicators with greatly improved fluorescence properties. , 1985, The Journal of biological chemistry.

[27]  A Grinvald,et al.  Localization of voltage-sensitive calcium channels along developing neurites: their possible role in regulating neurite elongation. , 1982, Developmental biology.

[28]  P G Nelson,et al.  Activity-dependent development of the vertebrate nervous system. , 1992, International review of neurobiology.

[29]  K. Lankford,et al.  Roles of actin filaments and three second-messenger systems in short-term regulation of chick dorsal root ganglion neurite outgrowth. , 1991, Cell motility and the cytoskeleton.

[30]  M. Schwarzschild,et al.  Acute regulation of tyrosine hydroxylase by nerve activity and by neurotransmitters via phosphorylation. , 1989, Annual review of neuroscience.