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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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Correlation between Naturally Occurring Variations in the Density of Presynaptic Cholinergic Terminals and Postsynaptic Dendritic Arbor Extension(A) The left column shows 3-D projections of cholinergic presynaptic profiles (Cha::Syt-GFP, anti-GFP staining) in the motor neuropile volumes (14.4 μm × 14.4 μm × 6 μm deep) containing the 18 h AEL aCC arbors depicted on the right. The presynaptic cholinergic profiles and their quantification were generated with the “Analyze Particles” ImageJ Plugin. aCC arbors are depicted as skeletons of reconstructions.(B) Correlation analysis of aCC dendritic tree length and the density of staining of the presynaptic cholinergic terminals in the motor neuropile. The dashed line indicates the linear best fit to the data points. The x-axis indicates synaptic density as the percentage of the neuropile volume containing staining for cholinergic presynaptic sites; the y-axis indicates total aCC dendritic length in micrometres in the same animal as the corresponding x-value; R2 = 0.6; F-value = 9; p = 0.02, n = 12.Scale bars indicate 5 μm.
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pbio-0060260-g009: Correlation between Naturally Occurring Variations in the Density of Presynaptic Cholinergic Terminals and Postsynaptic Dendritic Arbor Extension(A) The left column shows 3-D projections of cholinergic presynaptic profiles (Cha::Syt-GFP, anti-GFP staining) in the motor neuropile volumes (14.4 μm × 14.4 μm × 6 μm deep) containing the 18 h AEL aCC arbors depicted on the right. The presynaptic cholinergic profiles and their quantification were generated with the “Analyze Particles” ImageJ Plugin. aCC arbors are depicted as skeletons of reconstructions.(B) Correlation analysis of aCC dendritic tree length and the density of staining of the presynaptic cholinergic terminals in the motor neuropile. The dashed line indicates the linear best fit to the data points. The x-axis indicates synaptic density as the percentage of the neuropile volume containing staining for cholinergic presynaptic sites; the y-axis indicates total aCC dendritic length in micrometres in the same animal as the corresponding x-value; R2 = 0.6; F-value = 9; p = 0.02, n = 12.Scale bars indicate 5 μm.

Mentions: We put this prediction to the test. Using multiple control specimens, we first asked whether the density of presynaptic cholinergic terminals in the motor neuropile varies between control specimens. We find that it does (Figure 9A, left column). We then quantified the length of aCC dendritic trees in these specimens (Figure 9A, right column) and asked whether naturally occurring variations in the density of cholinergic terminals in the motor neuropile correlate with aCC dendritic arbor size. We find that there is a significant linear correlation between the density of cholinergic terminals in the motor neuropile and the extent of the aCC dendritic arbor (R2 = 0.6; F value = 9; p = 0.02, n = 9) (Figure 9B). A higher density of cholinergic terminals corresponds to a shorter postsynaptic dendritic arbor and vice versa (Figure 9A).


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)

Correlation between Naturally Occurring Variations in the Density of Presynaptic Cholinergic Terminals and Postsynaptic Dendritic Arbor Extension(A) The left column shows 3-D projections of cholinergic presynaptic profiles (Cha::Syt-GFP, anti-GFP staining) in the motor neuropile volumes (14.4 μm × 14.4 μm × 6 μm deep) containing the 18 h AEL aCC arbors depicted on the right. The presynaptic cholinergic profiles and their quantification were generated with the “Analyze Particles” ImageJ Plugin. aCC arbors are depicted as skeletons of reconstructions.(B) Correlation analysis of aCC dendritic tree length and the density of staining of the presynaptic cholinergic terminals in the motor neuropile. The dashed line indicates the linear best fit to the data points. The x-axis indicates synaptic density as the percentage of the neuropile volume containing staining for cholinergic presynaptic sites; the y-axis indicates total aCC dendritic length in micrometres in the same animal as the corresponding x-value; R2 = 0.6; F-value = 9; p = 0.02, n = 12.Scale bars indicate 5 μm.
© Copyright Policy
Related In: Results  -  Collection

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

pbio-0060260-g009: Correlation between Naturally Occurring Variations in the Density of Presynaptic Cholinergic Terminals and Postsynaptic Dendritic Arbor Extension(A) The left column shows 3-D projections of cholinergic presynaptic profiles (Cha::Syt-GFP, anti-GFP staining) in the motor neuropile volumes (14.4 μm × 14.4 μm × 6 μm deep) containing the 18 h AEL aCC arbors depicted on the right. The presynaptic cholinergic profiles and their quantification were generated with the “Analyze Particles” ImageJ Plugin. aCC arbors are depicted as skeletons of reconstructions.(B) Correlation analysis of aCC dendritic tree length and the density of staining of the presynaptic cholinergic terminals in the motor neuropile. The dashed line indicates the linear best fit to the data points. The x-axis indicates synaptic density as the percentage of the neuropile volume containing staining for cholinergic presynaptic sites; the y-axis indicates total aCC dendritic length in micrometres in the same animal as the corresponding x-value; R2 = 0.6; F-value = 9; p = 0.02, n = 12.Scale bars indicate 5 μm.
Mentions: We put this prediction to the test. Using multiple control specimens, we first asked whether the density of presynaptic cholinergic terminals in the motor neuropile varies between control specimens. We find that it does (Figure 9A, left column). We then quantified the length of aCC dendritic trees in these specimens (Figure 9A, right column) and asked whether naturally occurring variations in the density of cholinergic terminals in the motor neuropile correlate with aCC dendritic arbor size. We find that there is a significant linear correlation between the density of cholinergic terminals in the motor neuropile and the extent of the aCC dendritic arbor (R2 = 0.6; F value = 9; p = 0.02, n = 9) (Figure 9B). A higher density of cholinergic terminals corresponds to a shorter postsynaptic dendritic arbor and vice versa (Figure 9A).

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