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Intermingled cAMP, cGMP and calcium spatiotemporal dynamics in developing neuronal circuits.

Averaimo S, Nicol X - Front Cell Neurosci (2014)

Bottom Line: It is involved in a wide range of cellular processes that require independent regulation.However, our understanding of how this single second messenger achieves specific modulation of the signaling pathways involved remains incomplete.The subcellular compartmentalization and temporal regulation of cAMP signals have recently been identified as important coding strategies leading to specificity.

View Article: PubMed Central - PubMed

Affiliation: UMR_7210, Centre National de la Recherche Scientifique Paris, France ; UMR_S 968, Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06 Paris, France ; U968, Institut National de la Santé et de la Recherche Médicale Paris, France.

ABSTRACT
cAMP critically modulates the development of neuronal connectivity. It is involved in a wide range of cellular processes that require independent regulation. However, our understanding of how this single second messenger achieves specific modulation of the signaling pathways involved remains incomplete. The subcellular compartmentalization and temporal regulation of cAMP signals have recently been identified as important coding strategies leading to specificity. Dynamic interactions of this cyclic nucleotide with other second messenger including calcium and cGMP are critically involved in the regulation of spatiotemporal control of cAMP. Recent technical improvements of fluorescent sensors facilitate cAMP monitoring, whereas optogenetic tools permit spatial and temporal control of cAMP manipulations, all of which enabled the direct investigation of spatiotemporal characteristics of cAMP modulation in developing neurons. Focusing on neuronal polarization, neurotransmitter specification, axon guidance, and refinement of neuronal connectivity, we summarize herein the recent advances in understanding the features of cAMP signals and their dynamic interactions with calcium and cGMP involved in shaping the nervous system.

No MeSH data available.


Related in: MedlinePlus

Spatiotemporal dynamics of cAMP during developmental pruning of ectopic axonal branches, and synaptic competition. cAMP is required in two subcellular compartments during the synaptic refinement of neuronal projections. In the soma of retinal ganglion cells, cAMP oscillations and spontaneous calcium waves are interdependent. Spontaneous calcium waves are required for competition between axons in their targets. In the synapses, cAMP signaling mediated by adenylyl cyclases 1 and 8 is involved in synaptic potentiation and hebbian mechanisms, which are crucial to eliminate misplaced synapses.
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Figure 4: Spatiotemporal dynamics of cAMP during developmental pruning of ectopic axonal branches, and synaptic competition. cAMP is required in two subcellular compartments during the synaptic refinement of neuronal projections. In the soma of retinal ganglion cells, cAMP oscillations and spontaneous calcium waves are interdependent. Spontaneous calcium waves are required for competition between axons in their targets. In the synapses, cAMP signaling mediated by adenylyl cyclases 1 and 8 is involved in synaptic potentiation and hebbian mechanisms, which are crucial to eliminate misplaced synapses.

Mentions: Once axonal branches are positioned in their targets, they carefully choose their synaptic partners, often through an axonal or synaptic competition process. cAMP has a crucial role in modulating this competition that represents a critical process for the development of a properly organized neuronal connectivity (Luo and O’Leary, 2005; Luo and Flanagan, 2007). Competition is dependent on electrical activity, and its regulation by cAMP often relates to spontaneous activity generated during development (Penn et al., 1998; Stellwagen and Shatz, 2002; Zhang et al., 2012; Furman et al., 2013). In the developing retina, spontaneous calcium waves appear prior to vision. The frequency and propagation of these calcium waves are modulated by cAMP, with a higher frequency and a propagation over longer distances when cAMP is increased (Stellwagen et al., 1999; Stellwagen and Shatz, 2002). Interactions between cAMP and calcium waves in the developing retina are bidirectional: depolarization-induced calcium influx is sufficient to produce brief cAMP elevation, and cAMP transients are spontaneously generated in post-natal retinal ganglion cells (Dunn et al., 2006; Figure 4). Like the cAMP elevations observed in X. laevis spinal neurons, spontaneous cAMP / PKA activity transients in the developing retina are observed upon long but not short bursts of electrical activity (Gorbunova and Spitzer, 2002; Dunn et al., 2006). Surprisingly, the genetic removal of AC1, the main calcium-stimulated AC expressed in retinal ganglion cells, is not sufficient to perturb depolarization-induced cAMP elevations. In AC1/AC8 double knock-out mice, cAMP transients only exhibit a reduced amplitude and are abolished only with pharmacological blockade of both, transmembrane (AC1 to 9) and soluble (sAC/AC10) ACs, suggesting that several ACs cooperate to generate brief cAMP / PKA activity transients in the retina (Dunn et al., 2009).


Intermingled cAMP, cGMP and calcium spatiotemporal dynamics in developing neuronal circuits.

Averaimo S, Nicol X - Front Cell Neurosci (2014)

Spatiotemporal dynamics of cAMP during developmental pruning of ectopic axonal branches, and synaptic competition. cAMP is required in two subcellular compartments during the synaptic refinement of neuronal projections. In the soma of retinal ganglion cells, cAMP oscillations and spontaneous calcium waves are interdependent. Spontaneous calcium waves are required for competition between axons in their targets. In the synapses, cAMP signaling mediated by adenylyl cyclases 1 and 8 is involved in synaptic potentiation and hebbian mechanisms, which are crucial to eliminate misplaced synapses.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230202&req=5

Figure 4: Spatiotemporal dynamics of cAMP during developmental pruning of ectopic axonal branches, and synaptic competition. cAMP is required in two subcellular compartments during the synaptic refinement of neuronal projections. In the soma of retinal ganglion cells, cAMP oscillations and spontaneous calcium waves are interdependent. Spontaneous calcium waves are required for competition between axons in their targets. In the synapses, cAMP signaling mediated by adenylyl cyclases 1 and 8 is involved in synaptic potentiation and hebbian mechanisms, which are crucial to eliminate misplaced synapses.
Mentions: Once axonal branches are positioned in their targets, they carefully choose their synaptic partners, often through an axonal or synaptic competition process. cAMP has a crucial role in modulating this competition that represents a critical process for the development of a properly organized neuronal connectivity (Luo and O’Leary, 2005; Luo and Flanagan, 2007). Competition is dependent on electrical activity, and its regulation by cAMP often relates to spontaneous activity generated during development (Penn et al., 1998; Stellwagen and Shatz, 2002; Zhang et al., 2012; Furman et al., 2013). In the developing retina, spontaneous calcium waves appear prior to vision. The frequency and propagation of these calcium waves are modulated by cAMP, with a higher frequency and a propagation over longer distances when cAMP is increased (Stellwagen et al., 1999; Stellwagen and Shatz, 2002). Interactions between cAMP and calcium waves in the developing retina are bidirectional: depolarization-induced calcium influx is sufficient to produce brief cAMP elevation, and cAMP transients are spontaneously generated in post-natal retinal ganglion cells (Dunn et al., 2006; Figure 4). Like the cAMP elevations observed in X. laevis spinal neurons, spontaneous cAMP / PKA activity transients in the developing retina are observed upon long but not short bursts of electrical activity (Gorbunova and Spitzer, 2002; Dunn et al., 2006). Surprisingly, the genetic removal of AC1, the main calcium-stimulated AC expressed in retinal ganglion cells, is not sufficient to perturb depolarization-induced cAMP elevations. In AC1/AC8 double knock-out mice, cAMP transients only exhibit a reduced amplitude and are abolished only with pharmacological blockade of both, transmembrane (AC1 to 9) and soluble (sAC/AC10) ACs, suggesting that several ACs cooperate to generate brief cAMP / PKA activity transients in the retina (Dunn et al., 2009).

Bottom Line: It is involved in a wide range of cellular processes that require independent regulation.However, our understanding of how this single second messenger achieves specific modulation of the signaling pathways involved remains incomplete.The subcellular compartmentalization and temporal regulation of cAMP signals have recently been identified as important coding strategies leading to specificity.

View Article: PubMed Central - PubMed

Affiliation: UMR_7210, Centre National de la Recherche Scientifique Paris, France ; UMR_S 968, Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06 Paris, France ; U968, Institut National de la Santé et de la Recherche Médicale Paris, France.

ABSTRACT
cAMP critically modulates the development of neuronal connectivity. It is involved in a wide range of cellular processes that require independent regulation. However, our understanding of how this single second messenger achieves specific modulation of the signaling pathways involved remains incomplete. The subcellular compartmentalization and temporal regulation of cAMP signals have recently been identified as important coding strategies leading to specificity. Dynamic interactions of this cyclic nucleotide with other second messenger including calcium and cGMP are critically involved in the regulation of spatiotemporal control of cAMP. Recent technical improvements of fluorescent sensors facilitate cAMP monitoring, whereas optogenetic tools permit spatial and temporal control of cAMP manipulations, all of which enabled the direct investigation of spatiotemporal characteristics of cAMP modulation in developing neurons. Focusing on neuronal polarization, neurotransmitter specification, axon guidance, and refinement of neuronal connectivity, we summarize herein the recent advances in understanding the features of cAMP signals and their dynamic interactions with calcium and cGMP involved in shaping the nervous system.

No MeSH data available.


Related in: MedlinePlus