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Structural homeostasis: compensatory adjustments of dendritic arbor geometry in response to variations of synaptic input.

Tripodi M, Evers JF, Mauss A, Bate M, Landgraf M - PLoS Biol. (2008)

Bottom Line: Conversely, an increase in the density of presynaptic release sites induces a reduction in the extent of the dendritic arbor.These findings suggest that the dendritic arbor, at least during early stages of connectivity, behaves as a homeostatic device that adjusts its size and geometry to the level and the distribution of input received.The growing arbor thus counterbalances naturally occurring variations in synaptic density and activity so as to ensure that an appropriate level of input is achieved.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Cambridge, Cambridge, United Kingdom. ml10006@cam.ac.uk

ABSTRACT
As the nervous system develops, there is an inherent variability in the connections formed between differentiating neurons. Despite this variability, neural circuits form that are functional and remarkably robust. One way in which neurons deal with variability in their inputs is through compensatory, homeostatic changes in their electrical properties. Here, we show that neurons also make compensatory adjustments to their structure. We analysed the development of dendrites on an identified central neuron (aCC) in the late Drosophila embryo at the stage when it receives its first connections and first becomes electrically active. At the same time, we charted the distribution of presynaptic sites on the developing postsynaptic arbor. Genetic manipulations of the presynaptic partners demonstrate that the postsynaptic dendritic arbor adjusts its growth to compensate for changes in the activity and density of synaptic sites. Blocking the synthesis or evoked release of presynaptic neurotransmitter results in greater dendritic extension. Conversely, an increase in the density of presynaptic release sites induces a reduction in the extent of the dendritic arbor. These growth adjustments occur locally in the arbor and are the result of the promotion or inhibition of growth of neurites in the proximity of presynaptic sites. We provide evidence that suggest a role for the postsynaptic activity state of protein kinase A in mediating this structural adjustment, which modifies dendritic growth in response to synaptic activity. These findings suggest that the dendritic arbor, at least during early stages of connectivity, behaves as a homeostatic device that adjusts its size and geometry to the level and the distribution of input received. The growing arbor thus counterbalances naturally occurring variations in synaptic density and activity so as to ensure that an appropriate level of input is achieved.

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Model of the Role of Presynaptic Partners in Shaping Postsynaptic Dendritic ArborsCartoons of postsynaptic dendrites (green), presynaptic partner neurons (magenta), and synaptic sites (yellow).(A) In the wild type, (synaptic) contacts by presynaptic terminals act locally to restrict growth of the contacted postsynaptic neurites. This effect is independent of activity. Synaptic input exerts a second “extended” inhibitory effect on neighbouring nonsynaptic sister neurites. This second effect is activity dependent and mediated through PKA signalling.(B) In the absence of presynaptic neurotransmitter release (e.g., in Cha mutant and Cha::TNT-G animals), there is no activity-dependent, PKA-mediated “extended” inhibition. As a result, nonsynaptic neurites adjacent to presynaptic sites can continue to grow. In contrast, growth of synaptic neurites remains repressed by local contact-meditated, activity-independent mechanisms. Regions of the dendritic arbor that lack presynaptic input explore the neuropile further.(C) Increasing the density of active presynaptic terminals (e.g., in Cha::faf animals) leads to less extended and elaborate postsynaptic dendritic arbors. Active presynaptic sites are in immediate reach of dendrites and, after establishing contact, exert local contact-mediated and “extended” activity-dependent inhibition of further dendritic growth.(D) Displacement of presynaptic partner terminals (e.g., in Cha::Robo-Frazzled animals) eliminates contact with the postsynaptic arbor and thereby also relieves both local and “extended” inhibition. As a result, the postsynaptic arbor responds with extended growth.
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pbio-0060260-g010: Model of the Role of Presynaptic Partners in Shaping Postsynaptic Dendritic ArborsCartoons of postsynaptic dendrites (green), presynaptic partner neurons (magenta), and synaptic sites (yellow).(A) In the wild type, (synaptic) contacts by presynaptic terminals act locally to restrict growth of the contacted postsynaptic neurites. This effect is independent of activity. Synaptic input exerts a second “extended” inhibitory effect on neighbouring nonsynaptic sister neurites. This second effect is activity dependent and mediated through PKA signalling.(B) In the absence of presynaptic neurotransmitter release (e.g., in Cha mutant and Cha::TNT-G animals), there is no activity-dependent, PKA-mediated “extended” inhibition. As a result, nonsynaptic neurites adjacent to presynaptic sites can continue to grow. In contrast, growth of synaptic neurites remains repressed by local contact-meditated, activity-independent mechanisms. Regions of the dendritic arbor that lack presynaptic input explore the neuropile further.(C) Increasing the density of active presynaptic terminals (e.g., in Cha::faf animals) leads to less extended and elaborate postsynaptic dendritic arbors. Active presynaptic sites are in immediate reach of dendrites and, after establishing contact, exert local contact-mediated and “extended” activity-dependent inhibition of further dendritic growth.(D) Displacement of presynaptic partner terminals (e.g., in Cha::Robo-Frazzled animals) eliminates contact with the postsynaptic arbor and thereby also relieves both local and “extended” inhibition. As a result, the postsynaptic arbor responds with extended growth.

Mentions: This study shows that the postsynaptic dendritic arbor computes the synaptic input that it receives and adjusts its arborisation to compensate for variations in the activity and/or the density of the presynaptic input. Abolishing synaptic input induces a compensatory overgrowth of the postsynaptic dendritic arbor (Figure 10B). On the other hand, increasing the density of presynaptic sites produces the opposite effect, reducing the growth of the postsynaptic dendritic arbor (Figure 10C).


Structural homeostasis: compensatory adjustments of dendritic arbor geometry in response to variations of synaptic input.

Tripodi M, Evers JF, Mauss A, Bate M, Landgraf M - PLoS Biol. (2008)

Model of the Role of Presynaptic Partners in Shaping Postsynaptic Dendritic ArborsCartoons of postsynaptic dendrites (green), presynaptic partner neurons (magenta), and synaptic sites (yellow).(A) In the wild type, (synaptic) contacts by presynaptic terminals act locally to restrict growth of the contacted postsynaptic neurites. This effect is independent of activity. Synaptic input exerts a second “extended” inhibitory effect on neighbouring nonsynaptic sister neurites. This second effect is activity dependent and mediated through PKA signalling.(B) In the absence of presynaptic neurotransmitter release (e.g., in Cha mutant and Cha::TNT-G animals), there is no activity-dependent, PKA-mediated “extended” inhibition. As a result, nonsynaptic neurites adjacent to presynaptic sites can continue to grow. In contrast, growth of synaptic neurites remains repressed by local contact-meditated, activity-independent mechanisms. Regions of the dendritic arbor that lack presynaptic input explore the neuropile further.(C) Increasing the density of active presynaptic terminals (e.g., in Cha::faf animals) leads to less extended and elaborate postsynaptic dendritic arbors. Active presynaptic sites are in immediate reach of dendrites and, after establishing contact, exert local contact-mediated and “extended” activity-dependent inhibition of further dendritic growth.(D) Displacement of presynaptic partner terminals (e.g., in Cha::Robo-Frazzled animals) eliminates contact with the postsynaptic arbor and thereby also relieves both local and “extended” inhibition. As a result, the postsynaptic arbor responds with extended growth.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2573934&req=5

pbio-0060260-g010: Model of the Role of Presynaptic Partners in Shaping Postsynaptic Dendritic ArborsCartoons of postsynaptic dendrites (green), presynaptic partner neurons (magenta), and synaptic sites (yellow).(A) In the wild type, (synaptic) contacts by presynaptic terminals act locally to restrict growth of the contacted postsynaptic neurites. This effect is independent of activity. Synaptic input exerts a second “extended” inhibitory effect on neighbouring nonsynaptic sister neurites. This second effect is activity dependent and mediated through PKA signalling.(B) In the absence of presynaptic neurotransmitter release (e.g., in Cha mutant and Cha::TNT-G animals), there is no activity-dependent, PKA-mediated “extended” inhibition. As a result, nonsynaptic neurites adjacent to presynaptic sites can continue to grow. In contrast, growth of synaptic neurites remains repressed by local contact-meditated, activity-independent mechanisms. Regions of the dendritic arbor that lack presynaptic input explore the neuropile further.(C) Increasing the density of active presynaptic terminals (e.g., in Cha::faf animals) leads to less extended and elaborate postsynaptic dendritic arbors. Active presynaptic sites are in immediate reach of dendrites and, after establishing contact, exert local contact-mediated and “extended” activity-dependent inhibition of further dendritic growth.(D) Displacement of presynaptic partner terminals (e.g., in Cha::Robo-Frazzled animals) eliminates contact with the postsynaptic arbor and thereby also relieves both local and “extended” inhibition. As a result, the postsynaptic arbor responds with extended growth.
Mentions: This study shows that the postsynaptic dendritic arbor computes the synaptic input that it receives and adjusts its arborisation to compensate for variations in the activity and/or the density of the presynaptic input. Abolishing synaptic input induces a compensatory overgrowth of the postsynaptic dendritic arbor (Figure 10B). On the other hand, increasing the density of presynaptic sites produces the opposite effect, reducing the growth of the postsynaptic dendritic arbor (Figure 10C).

Bottom Line: Conversely, an increase in the density of presynaptic release sites induces a reduction in the extent of the dendritic arbor.These findings suggest that the dendritic arbor, at least during early stages of connectivity, behaves as a homeostatic device that adjusts its size and geometry to the level and the distribution of input received.The growing arbor thus counterbalances naturally occurring variations in synaptic density and activity so as to ensure that an appropriate level of input is achieved.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Cambridge, Cambridge, United Kingdom. ml10006@cam.ac.uk

ABSTRACT
As the nervous system develops, there is an inherent variability in the connections formed between differentiating neurons. Despite this variability, neural circuits form that are functional and remarkably robust. One way in which neurons deal with variability in their inputs is through compensatory, homeostatic changes in their electrical properties. Here, we show that neurons also make compensatory adjustments to their structure. We analysed the development of dendrites on an identified central neuron (aCC) in the late Drosophila embryo at the stage when it receives its first connections and first becomes electrically active. At the same time, we charted the distribution of presynaptic sites on the developing postsynaptic arbor. Genetic manipulations of the presynaptic partners demonstrate that the postsynaptic dendritic arbor adjusts its growth to compensate for changes in the activity and density of synaptic sites. Blocking the synthesis or evoked release of presynaptic neurotransmitter results in greater dendritic extension. Conversely, an increase in the density of presynaptic release sites induces a reduction in the extent of the dendritic arbor. These growth adjustments occur locally in the arbor and are the result of the promotion or inhibition of growth of neurites in the proximity of presynaptic sites. We provide evidence that suggest a role for the postsynaptic activity state of protein kinase A in mediating this structural adjustment, which modifies dendritic growth in response to synaptic activity. These findings suggest that the dendritic arbor, at least during early stages of connectivity, behaves as a homeostatic device that adjusts its size and geometry to the level and the distribution of input received. The growing arbor thus counterbalances naturally occurring variations in synaptic density and activity so as to ensure that an appropriate level of input is achieved.

Show MeSH
Related in: MedlinePlus