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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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Neurons Have Type-Specific Patterns of Dendritic Growth and Branching That Are Modulated Quantitatively, but Not Qualitatively, by Presynaptic Input(A) Reconstruction of a representative aCC dendritic arbor at 18 h AEL. Scale bar indicates 5 μm.(B) Correlation analysis between dendritic tree length (x-axis, micrometres) and number of branches (y-axis) of aCC at 18 h AEL in different conditions: control (red), Cha mutants (blue), and Cha::TNT-G (grey). R2 values are: controls (red), R2 = 0.75, F-value = 33, p < 0.05, n = 13; Cha mutants (blue), R2 = 0.64, F-value = 11, p < 0.05, n = 10; in Cha::TNT-G (yellow), R2 = 0.65, n = 10, F-value = 11, p < 0.05, n = 10. Dashed lines indicate the slopes of the samples.(C) Bar plots (mean ± standard error of the mean [SEM]) of the ratio between total tree length (in micrometres) and number of branch points in control (red), Cha mutant (blue), and Cha::TNT-G animals (grey).(D) Reconstruction of a representative RP1 arbor at 18 h AEL. Scale bar indicates 5 μm.(E) Correlation analysis between dendritic tree length (x-axis, micrometres) and number of branches (y-axis) of aCC (red) and RP1 (green) at 18 h AEL. Both neurons have a linear relationship between tree length and branch number, R2 = 0.93, F-value = 25, p < 0.05, n = 5. Dashed lines indicate the slope of the samples.(F) Ratios of tree length/branch number for aCC (red) and RP1 (green). The two differ significantly. Significance was assessed by unpaired, two-tailed t-test. Double asterisks (**) indicate p < 0.005, and NS indicates p > 0.05. Mean ± SEM.In all reconstructions, dendrites are pseudocoloured yellow and the axon blue.
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pbio-0060260-g003: Neurons Have Type-Specific Patterns of Dendritic Growth and Branching That Are Modulated Quantitatively, but Not Qualitatively, by Presynaptic Input(A) Reconstruction of a representative aCC dendritic arbor at 18 h AEL. Scale bar indicates 5 μm.(B) Correlation analysis between dendritic tree length (x-axis, micrometres) and number of branches (y-axis) of aCC at 18 h AEL in different conditions: control (red), Cha mutants (blue), and Cha::TNT-G (grey). R2 values are: controls (red), R2 = 0.75, F-value = 33, p < 0.05, n = 13; Cha mutants (blue), R2 = 0.64, F-value = 11, p < 0.05, n = 10; in Cha::TNT-G (yellow), R2 = 0.65, n = 10, F-value = 11, p < 0.05, n = 10. Dashed lines indicate the slopes of the samples.(C) Bar plots (mean ± standard error of the mean [SEM]) of the ratio between total tree length (in micrometres) and number of branch points in control (red), Cha mutant (blue), and Cha::TNT-G animals (grey).(D) Reconstruction of a representative RP1 arbor at 18 h AEL. Scale bar indicates 5 μm.(E) Correlation analysis between dendritic tree length (x-axis, micrometres) and number of branches (y-axis) of aCC (red) and RP1 (green) at 18 h AEL. Both neurons have a linear relationship between tree length and branch number, R2 = 0.93, F-value = 25, p < 0.05, n = 5. Dashed lines indicate the slope of the samples.(F) Ratios of tree length/branch number for aCC (red) and RP1 (green). The two differ significantly. Significance was assessed by unpaired, two-tailed t-test. Double asterisks (**) indicate p < 0.005, and NS indicates p > 0.05. Mean ± SEM.In all reconstructions, dendrites are pseudocoloured yellow and the axon blue.

Mentions: It is conceivable that we observed a constant ratio between tree length and branch numbers under different experimental conditions because it reflects mechanical or cell biological constraints. If this were the case, then other neurons would be predicted to have the same ratio of tree length to branch number as aCC. To test this hypothesis, we analysed the arborisation pattern of another motor neuron, RP1. The RP1 motor neuron also shows a linear relation between tree length and branch points (R2 = 0.93, F-value = 25, p < 0.05, n = 5). However, in the case of RP1, the ratio between tree length and branch points is significantly different from that observed for aCC (compare the two average tree-length/branch-point ratios in Figure 3F, p = 0.001, unpaired, two-tailed t-test, no equal variance assumed).


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)

Neurons Have Type-Specific Patterns of Dendritic Growth and Branching That Are Modulated Quantitatively, but Not Qualitatively, by Presynaptic Input(A) Reconstruction of a representative aCC dendritic arbor at 18 h AEL. Scale bar indicates 5 μm.(B) Correlation analysis between dendritic tree length (x-axis, micrometres) and number of branches (y-axis) of aCC at 18 h AEL in different conditions: control (red), Cha mutants (blue), and Cha::TNT-G (grey). R2 values are: controls (red), R2 = 0.75, F-value = 33, p < 0.05, n = 13; Cha mutants (blue), R2 = 0.64, F-value = 11, p < 0.05, n = 10; in Cha::TNT-G (yellow), R2 = 0.65, n = 10, F-value = 11, p < 0.05, n = 10. Dashed lines indicate the slopes of the samples.(C) Bar plots (mean ± standard error of the mean [SEM]) of the ratio between total tree length (in micrometres) and number of branch points in control (red), Cha mutant (blue), and Cha::TNT-G animals (grey).(D) Reconstruction of a representative RP1 arbor at 18 h AEL. Scale bar indicates 5 μm.(E) Correlation analysis between dendritic tree length (x-axis, micrometres) and number of branches (y-axis) of aCC (red) and RP1 (green) at 18 h AEL. Both neurons have a linear relationship between tree length and branch number, R2 = 0.93, F-value = 25, p < 0.05, n = 5. Dashed lines indicate the slope of the samples.(F) Ratios of tree length/branch number for aCC (red) and RP1 (green). The two differ significantly. Significance was assessed by unpaired, two-tailed t-test. Double asterisks (**) indicate p < 0.005, and NS indicates p > 0.05. Mean ± SEM.In all reconstructions, dendrites are pseudocoloured yellow and the axon blue.
© Copyright Policy
Related In: Results  -  Collection

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

pbio-0060260-g003: Neurons Have Type-Specific Patterns of Dendritic Growth and Branching That Are Modulated Quantitatively, but Not Qualitatively, by Presynaptic Input(A) Reconstruction of a representative aCC dendritic arbor at 18 h AEL. Scale bar indicates 5 μm.(B) Correlation analysis between dendritic tree length (x-axis, micrometres) and number of branches (y-axis) of aCC at 18 h AEL in different conditions: control (red), Cha mutants (blue), and Cha::TNT-G (grey). R2 values are: controls (red), R2 = 0.75, F-value = 33, p < 0.05, n = 13; Cha mutants (blue), R2 = 0.64, F-value = 11, p < 0.05, n = 10; in Cha::TNT-G (yellow), R2 = 0.65, n = 10, F-value = 11, p < 0.05, n = 10. Dashed lines indicate the slopes of the samples.(C) Bar plots (mean ± standard error of the mean [SEM]) of the ratio between total tree length (in micrometres) and number of branch points in control (red), Cha mutant (blue), and Cha::TNT-G animals (grey).(D) Reconstruction of a representative RP1 arbor at 18 h AEL. Scale bar indicates 5 μm.(E) Correlation analysis between dendritic tree length (x-axis, micrometres) and number of branches (y-axis) of aCC (red) and RP1 (green) at 18 h AEL. Both neurons have a linear relationship between tree length and branch number, R2 = 0.93, F-value = 25, p < 0.05, n = 5. Dashed lines indicate the slope of the samples.(F) Ratios of tree length/branch number for aCC (red) and RP1 (green). The two differ significantly. Significance was assessed by unpaired, two-tailed t-test. Double asterisks (**) indicate p < 0.005, and NS indicates p > 0.05. Mean ± SEM.In all reconstructions, dendrites are pseudocoloured yellow and the axon blue.
Mentions: It is conceivable that we observed a constant ratio between tree length and branch numbers under different experimental conditions because it reflects mechanical or cell biological constraints. If this were the case, then other neurons would be predicted to have the same ratio of tree length to branch number as aCC. To test this hypothesis, we analysed the arborisation pattern of another motor neuron, RP1. The RP1 motor neuron also shows a linear relation between tree length and branch points (R2 = 0.93, F-value = 25, p < 0.05, n = 5). However, in the case of RP1, the ratio between tree length and branch points is significantly different from that observed for aCC (compare the two average tree-length/branch-point ratios in Figure 3F, p = 0.001, unpaired, two-tailed t-test, no equal variance assumed).

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