Stimulus History Alters Behavioral Responses of Neuronal Growth Cones

Diefenbach, Thomas; Guthrie, Peter B.; Kater, Stanley B.

doi:10.1523/jneurosci.20-04-01484.2000

Cited by 32 publications

(21 citation statements)

References 70 publications

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“…Electrical activity regulates axonal growth cone motility It has long been known that long-term electrical stimulation of neurons (several minutes to days) inhibits axon outgrowth (Cohan and Kater, 1986;Fields et al, 1990;Diefenbach et al, 2000). However, contrary to the long stimulation periods tested so far, the patterns of electrical activity observed in vivo are often structured in bursts only lasting seconds to 1 min at most (O'Donovan, 1999;Ben-Ari, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Longer stimulations eventually lead to growth cone collapse (Diefenbach et al, 2000). In addition, electrical activity could control the integration by growth cones of signals arising from local cues.…”

Section: Electrical Activity and The Formation Of Neuronal Connectivitymentioning

confidence: 99%

“…Although electrical activity is essential for the correct formation of neural circuits (Goodman and Shatz, 1993;Zhang and Poo, 2001), the mechanisms whereby early spontaneous activity may influence axonal growth and the establishment of synapses have remained elusive. Sustained electrical stimulation for long periods (Ͼ10 min to days) inhibits axon elongation and eventually causes growth cone collapse (Cohan and Kater, 1986;Fields et al, 1990;Diefenbach et al, 2000). However, because electrical activity is intermittent in the developing brain and because neurotransmitters are expected to act on a short timescale before they are eliminated, it is important to assess whether transient excitations of neurons also affect growth cone behavior.…”

Section: Introductionmentioning

confidence: 99%

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Fast Regulation of Axonal Growth Cone Motility by Electrical Activity

Ibarretxe¹,

Perrais²,

Jaskolski³

et al. 2007

J. Neurosci.

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Axonal growth cones are responsible for the correct guidance of developing axons and the establishment of functional neural networks. They are highly motile because of fast and continuous rearrangements of their actin-rich cytoskeleton. Here we have used live imaging of axonal growth cones of hippocampal neurons in culture and quantified their motility with a temporal resolution of 2 s. Using novel methods of analysis of growth cone dynamics, we show that transient activation of kainate receptors by bath-applied kainate induced a fast and reversible growth cone stalling. This effect depends on electrical activity and can be mimicked by the transient discharge of action potentials elicited in the neuron by intracellular current injections at the somatic level through a patch pipette. Growth cone stalling induced by electrical stimulation is mediated by calcium entry from the extracellular medium as well as by calcium release from intracellular stores that define spatially restricted microdomains directly affecting cytoskeletal dynamics. We propose that growth cone motility is dynamically controlled by transient bursts of spontaneous electrical activity, which constitutes a prominent feature of developing neural networks in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Electrical Activity and The Formation Of Neuronal Connectivitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fast Regulation of Axonal Growth Cone Motility by Electrical Activity

Ibarretxe¹,

Perrais²,

Jaskolski³

et al. 2007

J. Neurosci.

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“…To inhibit PKA activity, presynaptic neurons were incubated selectively in H-89 (Calbiochem, La Jolla, CA) (Zhang et al, 2002) or KT5720 (Calbiochem) (Diefenbach et al, 2000), which were dissolved in DMSO (final [DMSO] Ͻ0.01%). 8Br-cAMP (Research Biochemicals, Natick, MA) and acetylcholine were dissolved in water.…”

Section: Methodsmentioning

confidence: 99%

Synapse Number and Synaptic Efficacy Are Regulated by Presynaptic cAMP and Protein Kinase A

2003

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The mechanisms by which neurons regulate the number and strength of synapses during development and synaptic plasticity have not yet been defined fully. This lack of fundamental knowledge in the fields of neurodevelopment and synaptic plasticity can be attributed, in part, to compensatory mechanisms by which neurons accommodate for the loss of function in their synaptic partners. This is generally achieved either by scaling up neuronal transmitter release capabilities or by enhancing the postsynaptic responsiveness. Here, we demonstrate that regulation of synaptic strength and number between identified Lymnaea neurons visceral dorsal 4 (VD4, the presynaptic cell) and left pedal dorsal 1 (LPeD1, the postsynaptic cell) requires presynaptic activation of a cAMP-PKA-dependent signal. Experimental activation of the cAMP-PKA pathway resulted in reduced synaptic efficacy, whereas inhibition of the cAMP-PKA cascade permitted hyperinnervation and an overall enhancement of synaptic strength. Because synaptic transmission between VD4 and LPeD1 does not require a cAMP-PKA pathway, our data show that these messengers may play a novel role in regulating the synaptic efficacy during early synaptogenesis and plasticity.

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“…It is known that the growth cone's behaviour is dependent on the history of previous stimulation [100]. Similarly, the response of Dictyostelium cells to extracellular signals is strongly dependent on the initial intracellular bias [20].…”

Section: A Bayesian Framework For Gradient Sensingmentioning

confidence: 99%

Mathematical modelling of axon guidance in chemical gradients

Nguyen¹

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Correct wiring is crucial to the proper functioning of the nervous system. Key signals guiding growth cones, the motile tips of developing axons, to their targets are molecular gradients. The receptors on the membrane of the growth cone bind stochastically with guidance molecules in the environment, giving an estimate of the direction of the gradient. The growth cone then executes biased random movements to navigate toward the chemoattractant source or away from the chemorepellent source. This thesis addresses two questions: 1) how the positioning and diffusion of receptors on the growth cone membrane affect the accuracy of gradient estimation, 2) how trajectories are influenced by chemical gradients.Membrane receptors can diffuse freely on the membrane, smearing out the directional information about the gradient. It was unknown how the positioning and diffusion of receptors affect the estimate of the gradient. To address question (1) above, we utilise an ideal-observer approach, assuming that the growth cone can perform maximum likelihood estimation of the gradient based on the stochastic binding patterns with ligand molecules. The performance of gradient sensing is measured by the Fisher Information between the binding pattern and the gradient direction. The quality of gradient sensing decreases with higher diffusion constant of the receptors and improves with higher concentration. We then extend to a two-dimensional model of an elliptical growth cone with a general prior distribution. With a random uniform distribution of receptors, the shape of the growth cone can introduce bias in the gradient estimate. This bias can be corrected by a non-uniform distribution of receptors with higher density near the minor axis of the growth cone.Besides stochastic gradient sensing, growth cones also trace highly stochastic trajectories, and it is unclear how molecular gradients bias their movement. We then introduce a mathematical model of a correlated random walk based on persistence, bias and noise to describe growth cone trajectories, constrained directly by measurements of the detailed statistics of growth cone movements in both attractive and repulsive gradients in a microfluidic device. This model explains the long-standing mystery that average axon turning angles in gradients in vitro plateau very rapidly with time at relatively small values of 10-20• . This work introduces the most accurate predictive model of growth cone trajectories to date, and calls into question the ability of molecular gradients alone to provide reliable guidance cues for growing axons.ii Declaration by AuthorThis thesis is composed of my original work, and contains no material previously published or written by another person except where due reference has been made in the text. I have clearly stated the contribution by others to jointly-authored works that I have included in my thesis.

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Stimulus History Alters Behavioral Responses of Neuronal Growth Cones

Cited by 32 publications

References 70 publications

Fast Regulation of Axonal Growth Cone Motility by Electrical Activity

Fast Regulation of Axonal Growth Cone Motility by Electrical Activity

Synapse Number and Synaptic Efficacy Are Regulated by Presynaptic cAMP and Protein Kinase A

Mathematical modelling of axon guidance in chemical gradients

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