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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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Presynaptic Sites Induce an Activity-Independent Local Inhibition of Postsynaptic Dendritic Growth(A–C) Single confocal sections of a Lucifer Yellow–labelled aCC at 16 h AEL (pseudocoloured green), cholinergic presynaptic sites (Cha::SytGFP, pseudocoloured magenta), and the overlay of the two channels, respectively.(D) Reconstruction of the aCC arbor shown in (A), areas of contact with the arbor colour coded to represent relative intensities of colocalised fluorescence signals.(E–H) As for (A–D), but for Cha mutants at 16 h AEL.(I–L) As for (A–D), but for animals in which the chimeric receptor Roboectodomain-Frazzledcytoplasmic (Robo-Frazzled) has been expressed in the cholinergic neurons.(M and N) Projections of the dorsal neuropile in control (M) and Cha::Robo-Frazzled (N) animals showing presynaptic cholinergic terminals (red), and FasII-positive fascicles (blue). In Cha::Robo-Frazzled (N) animals, terminals are shifted from lateral and intermediate (as demarcated by the lateral and intermediate FasII-positive fascicles [arrowheads]) to medial regions of the neuropile (the ventral midline is indicated by dashed lines).(O and P) Projections of cholinergic presynaptic sites in the posterior commissure. Two adjacent abdominal segments are shown. There is a marked increased width of the posterior commissure, indicated by white bar on ventral midline, in Cha::Robo-Fra (P) as compared to control (O) animals.(Q) Quantification of aCC total dendritic tree length at 16 h and 18 h AEL for controls (red, Cha mutant (blue), and Cha::Robo-Frazzled (cyan) animals. Box-plots show the median of the distribution (middle line), the 75th percentile (upper limit of box), and 25th percentile (lower limit of box). Whiskers indicate the highest and lowest value of each experimental group. Significance was assessed by unpaired, two-tailed t-test; double asterisks (**) indicate p < 0.005, and NS indicate p > 0.05. Scale bars indicate 5 μm.
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pbio-0060260-g007: Presynaptic Sites Induce an Activity-Independent Local Inhibition of Postsynaptic Dendritic Growth(A–C) Single confocal sections of a Lucifer Yellow–labelled aCC at 16 h AEL (pseudocoloured green), cholinergic presynaptic sites (Cha::SytGFP, pseudocoloured magenta), and the overlay of the two channels, respectively.(D) Reconstruction of the aCC arbor shown in (A), areas of contact with the arbor colour coded to represent relative intensities of colocalised fluorescence signals.(E–H) As for (A–D), but for Cha mutants at 16 h AEL.(I–L) As for (A–D), but for animals in which the chimeric receptor Roboectodomain-Frazzledcytoplasmic (Robo-Frazzled) has been expressed in the cholinergic neurons.(M and N) Projections of the dorsal neuropile in control (M) and Cha::Robo-Frazzled (N) animals showing presynaptic cholinergic terminals (red), and FasII-positive fascicles (blue). In Cha::Robo-Frazzled (N) animals, terminals are shifted from lateral and intermediate (as demarcated by the lateral and intermediate FasII-positive fascicles [arrowheads]) to medial regions of the neuropile (the ventral midline is indicated by dashed lines).(O and P) Projections of cholinergic presynaptic sites in the posterior commissure. Two adjacent abdominal segments are shown. There is a marked increased width of the posterior commissure, indicated by white bar on ventral midline, in Cha::Robo-Fra (P) as compared to control (O) animals.(Q) Quantification of aCC total dendritic tree length at 16 h and 18 h AEL for controls (red, Cha mutant (blue), and Cha::Robo-Frazzled (cyan) animals. Box-plots show the median of the distribution (middle line), the 75th percentile (upper limit of box), and 25th percentile (lower limit of box). Whiskers indicate the highest and lowest value of each experimental group. Significance was assessed by unpaired, two-tailed t-test; double asterisks (**) indicate p < 0.005, and NS indicate p > 0.05. Scale bars indicate 5 μm.

Mentions: These results suggest that the local inhibition of dendritic growth at the site where putative synapses form depends on mechanisms other than evoked release. This hypothesis predicts that the postsynaptic dendritic arbor would respond with overgrowth to the absence of contact with presynaptic partner terminals. To test this, we sought to prevent the normal formation of contacts between pre- and postsynaptic partners by shifting the presynaptic terminals of cholinergic neurons to a more medial portion of the neuropile. To do so, we expressed in the cholinergic cells (with Cha-GAL4) the chimeric Roboectodomain-Frazzledcytoplasmic guidance receptor, which has been shown to induce a strong medial shift of axons [32]. The expression of this chimeric receptor in the cholinergic population does indeed induce a shift of cholinergic synaptic terminals out of the lateral and into the medial neuropile (compare Figure 7M with 7N and Figure 7O with 7P).


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)

Presynaptic Sites Induce an Activity-Independent Local Inhibition of Postsynaptic Dendritic Growth(A–C) Single confocal sections of a Lucifer Yellow–labelled aCC at 16 h AEL (pseudocoloured green), cholinergic presynaptic sites (Cha::SytGFP, pseudocoloured magenta), and the overlay of the two channels, respectively.(D) Reconstruction of the aCC arbor shown in (A), areas of contact with the arbor colour coded to represent relative intensities of colocalised fluorescence signals.(E–H) As for (A–D), but for Cha mutants at 16 h AEL.(I–L) As for (A–D), but for animals in which the chimeric receptor Roboectodomain-Frazzledcytoplasmic (Robo-Frazzled) has been expressed in the cholinergic neurons.(M and N) Projections of the dorsal neuropile in control (M) and Cha::Robo-Frazzled (N) animals showing presynaptic cholinergic terminals (red), and FasII-positive fascicles (blue). In Cha::Robo-Frazzled (N) animals, terminals are shifted from lateral and intermediate (as demarcated by the lateral and intermediate FasII-positive fascicles [arrowheads]) to medial regions of the neuropile (the ventral midline is indicated by dashed lines).(O and P) Projections of cholinergic presynaptic sites in the posterior commissure. Two adjacent abdominal segments are shown. There is a marked increased width of the posterior commissure, indicated by white bar on ventral midline, in Cha::Robo-Fra (P) as compared to control (O) animals.(Q) Quantification of aCC total dendritic tree length at 16 h and 18 h AEL for controls (red, Cha mutant (blue), and Cha::Robo-Frazzled (cyan) animals. Box-plots show the median of the distribution (middle line), the 75th percentile (upper limit of box), and 25th percentile (lower limit of box). Whiskers indicate the highest and lowest value of each experimental group. Significance was assessed by unpaired, two-tailed t-test; double asterisks (**) indicate p < 0.005, and NS indicate p > 0.05. Scale bars indicate 5 μm.
© Copyright Policy
Related In: Results  -  Collection

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

pbio-0060260-g007: Presynaptic Sites Induce an Activity-Independent Local Inhibition of Postsynaptic Dendritic Growth(A–C) Single confocal sections of a Lucifer Yellow–labelled aCC at 16 h AEL (pseudocoloured green), cholinergic presynaptic sites (Cha::SytGFP, pseudocoloured magenta), and the overlay of the two channels, respectively.(D) Reconstruction of the aCC arbor shown in (A), areas of contact with the arbor colour coded to represent relative intensities of colocalised fluorescence signals.(E–H) As for (A–D), but for Cha mutants at 16 h AEL.(I–L) As for (A–D), but for animals in which the chimeric receptor Roboectodomain-Frazzledcytoplasmic (Robo-Frazzled) has been expressed in the cholinergic neurons.(M and N) Projections of the dorsal neuropile in control (M) and Cha::Robo-Frazzled (N) animals showing presynaptic cholinergic terminals (red), and FasII-positive fascicles (blue). In Cha::Robo-Frazzled (N) animals, terminals are shifted from lateral and intermediate (as demarcated by the lateral and intermediate FasII-positive fascicles [arrowheads]) to medial regions of the neuropile (the ventral midline is indicated by dashed lines).(O and P) Projections of cholinergic presynaptic sites in the posterior commissure. Two adjacent abdominal segments are shown. There is a marked increased width of the posterior commissure, indicated by white bar on ventral midline, in Cha::Robo-Fra (P) as compared to control (O) animals.(Q) Quantification of aCC total dendritic tree length at 16 h and 18 h AEL for controls (red, Cha mutant (blue), and Cha::Robo-Frazzled (cyan) animals. Box-plots show the median of the distribution (middle line), the 75th percentile (upper limit of box), and 25th percentile (lower limit of box). Whiskers indicate the highest and lowest value of each experimental group. Significance was assessed by unpaired, two-tailed t-test; double asterisks (**) indicate p < 0.005, and NS indicate p > 0.05. Scale bars indicate 5 μm.
Mentions: These results suggest that the local inhibition of dendritic growth at the site where putative synapses form depends on mechanisms other than evoked release. This hypothesis predicts that the postsynaptic dendritic arbor would respond with overgrowth to the absence of contact with presynaptic partner terminals. To test this, we sought to prevent the normal formation of contacts between pre- and postsynaptic partners by shifting the presynaptic terminals of cholinergic neurons to a more medial portion of the neuropile. To do so, we expressed in the cholinergic cells (with Cha-GAL4) the chimeric Roboectodomain-Frazzledcytoplasmic guidance receptor, which has been shown to induce a strong medial shift of axons [32]. The expression of this chimeric receptor in the cholinergic population does indeed induce a shift of cholinergic synaptic terminals out of the lateral and into the medial neuropile (compare Figure 7M with 7N and Figure 7O with 7P).

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