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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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Lack of Presynaptic Neurotransmitter Induces Overgrowth of the Postsynaptic aCC Dendritic Arbor(A, C, and E) Reconstructions from confocal image stacks of representative aCC arbors at 18 h AEL. (A) control, (B) Cha mutants, and (C) tetanus toxin expressed in presynaptic neurons. Arrowheads in (C) and (E) indicate branches that show extra growth into neuropile territories not normally invaded. The dendrites are pseudocoloured yellow, and the axon blue. Anterior is left. Scale bar indicates 5 μm.(B) Growth curves of aCC dendritic trees in control (red) and Cha mutant animals (blue): the y-axis indicates total tree length in μm; the x-axis indicates developmental stage in hours AEL. AP, action potentials elicited in aCC by presynaptic inputs; NS indicates p > 0.05.(D) Quantification of dendritic tree length at 18 h AEL in control (red), Cha mutant (blue), and Cha::TNT-G animals (grey). 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. A single asterisk (*) indicates p < 0.05.(F) Sholl analysis for control neurons (red), Cha mutant (blue), and Cha::TNT-G (grey) animals. The axon was defined as origin. The y-axis indicates number of segment intersections; the x-axis indicates distance from the axon (origin) in micrometres. Error bars in B and F indicate SEM.
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pbio-0060260-g002: Lack of Presynaptic Neurotransmitter Induces Overgrowth of the Postsynaptic aCC Dendritic Arbor(A, C, and E) Reconstructions from confocal image stacks of representative aCC arbors at 18 h AEL. (A) control, (B) Cha mutants, and (C) tetanus toxin expressed in presynaptic neurons. Arrowheads in (C) and (E) indicate branches that show extra growth into neuropile territories not normally invaded. The dendrites are pseudocoloured yellow, and the axon blue. Anterior is left. Scale bar indicates 5 μm.(B) Growth curves of aCC dendritic trees in control (red) and Cha mutant animals (blue): the y-axis indicates total tree length in μm; the x-axis indicates developmental stage in hours AEL. AP, action potentials elicited in aCC by presynaptic inputs; NS indicates p > 0.05.(D) Quantification of dendritic tree length at 18 h AEL in control (red), Cha mutant (blue), and Cha::TNT-G animals (grey). 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. A single asterisk (*) indicates p < 0.05.(F) Sholl analysis for control neurons (red), Cha mutant (blue), and Cha::TNT-G (grey) animals. The axon was defined as origin. The y-axis indicates number of segment intersections; the x-axis indicates distance from the axon (origin) in micrometres. Error bars in B and F indicate SEM.

Mentions: Since cholinergic neurons provide the only known excitatory input to Drosophila motor neurons in the embryo [16], we first analyzed the effect of the lack of neurotransmitter (synthesis) in the cholinergic neurons on the development of the aCC dendritic arbor. Acetyl choline is not synthesized in animals mutant for choline acetyl transferase (Chal13) [24], which are therefore immobile and unable to hatch. We charted the development of aCC dendritic arborisations in animals homozygous for the mutation Chal13 [24]. In Cha mutant embryos, we find that the development of the aCC dendritic arbor proceeds normally until 16 h AEL (Figure 2B). However, in the interval between 16 to 18 h AEL, Cha mutants, unlike controls, fail to reduce the rate of dendritic growth (Figure 2B). As a result, at 18 h AEL, the extent of the aCC dendritic arbor is increased by about 26% in Cha mutants as compared to controls (from 115 ± 7 μm in control animals, n = 13; to 145 ± 14 μm in Cha mutants, n = 10, p = 0.03) (Figure 2B, compare Figure 2A with Figure 2C). We conclude that in the window of development, when in normal embryos acetyl choline–dependent excitation of aCC first begins [16] and the rate of dendritic growth declines, the absence of neurotransmitter in presynaptic neurons allows postsynaptic growth to continue linearly at an undiminished constant rate. These findings suggest that the aCC dendritic arbor reacts to the loss of synaptic input by increasing in size. A consequence of this increase in overall dendritic length is that it allows the dendritic arbor to explore a larger portion of the neuropile than in normal animals. In fact, we observe that in Cha mutants, the dendritic arbor of aCC extends into regions of the neuropile that are not normally invaded in control conditions (Figure 2C, arrowhead). This change in the dendritic distribution is also confirmed by the shift of the peak in the Sholl analysis (Figure 2F).


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)

Lack of Presynaptic Neurotransmitter Induces Overgrowth of the Postsynaptic aCC Dendritic Arbor(A, C, and E) Reconstructions from confocal image stacks of representative aCC arbors at 18 h AEL. (A) control, (B) Cha mutants, and (C) tetanus toxin expressed in presynaptic neurons. Arrowheads in (C) and (E) indicate branches that show extra growth into neuropile territories not normally invaded. The dendrites are pseudocoloured yellow, and the axon blue. Anterior is left. Scale bar indicates 5 μm.(B) Growth curves of aCC dendritic trees in control (red) and Cha mutant animals (blue): the y-axis indicates total tree length in μm; the x-axis indicates developmental stage in hours AEL. AP, action potentials elicited in aCC by presynaptic inputs; NS indicates p > 0.05.(D) Quantification of dendritic tree length at 18 h AEL in control (red), Cha mutant (blue), and Cha::TNT-G animals (grey). 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. A single asterisk (*) indicates p < 0.05.(F) Sholl analysis for control neurons (red), Cha mutant (blue), and Cha::TNT-G (grey) animals. The axon was defined as origin. The y-axis indicates number of segment intersections; the x-axis indicates distance from the axon (origin) in micrometres. Error bars in B and F indicate SEM.
© Copyright Policy
Related In: Results  -  Collection

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

pbio-0060260-g002: Lack of Presynaptic Neurotransmitter Induces Overgrowth of the Postsynaptic aCC Dendritic Arbor(A, C, and E) Reconstructions from confocal image stacks of representative aCC arbors at 18 h AEL. (A) control, (B) Cha mutants, and (C) tetanus toxin expressed in presynaptic neurons. Arrowheads in (C) and (E) indicate branches that show extra growth into neuropile territories not normally invaded. The dendrites are pseudocoloured yellow, and the axon blue. Anterior is left. Scale bar indicates 5 μm.(B) Growth curves of aCC dendritic trees in control (red) and Cha mutant animals (blue): the y-axis indicates total tree length in μm; the x-axis indicates developmental stage in hours AEL. AP, action potentials elicited in aCC by presynaptic inputs; NS indicates p > 0.05.(D) Quantification of dendritic tree length at 18 h AEL in control (red), Cha mutant (blue), and Cha::TNT-G animals (grey). 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. A single asterisk (*) indicates p < 0.05.(F) Sholl analysis for control neurons (red), Cha mutant (blue), and Cha::TNT-G (grey) animals. The axon was defined as origin. The y-axis indicates number of segment intersections; the x-axis indicates distance from the axon (origin) in micrometres. Error bars in B and F indicate SEM.
Mentions: Since cholinergic neurons provide the only known excitatory input to Drosophila motor neurons in the embryo [16], we first analyzed the effect of the lack of neurotransmitter (synthesis) in the cholinergic neurons on the development of the aCC dendritic arbor. Acetyl choline is not synthesized in animals mutant for choline acetyl transferase (Chal13) [24], which are therefore immobile and unable to hatch. We charted the development of aCC dendritic arborisations in animals homozygous for the mutation Chal13 [24]. In Cha mutant embryos, we find that the development of the aCC dendritic arbor proceeds normally until 16 h AEL (Figure 2B). However, in the interval between 16 to 18 h AEL, Cha mutants, unlike controls, fail to reduce the rate of dendritic growth (Figure 2B). As a result, at 18 h AEL, the extent of the aCC dendritic arbor is increased by about 26% in Cha mutants as compared to controls (from 115 ± 7 μm in control animals, n = 13; to 145 ± 14 μm in Cha mutants, n = 10, p = 0.03) (Figure 2B, compare Figure 2A with Figure 2C). We conclude that in the window of development, when in normal embryos acetyl choline–dependent excitation of aCC first begins [16] and the rate of dendritic growth declines, the absence of neurotransmitter in presynaptic neurons allows postsynaptic growth to continue linearly at an undiminished constant rate. These findings suggest that the aCC dendritic arbor reacts to the loss of synaptic input by increasing in size. A consequence of this increase in overall dendritic length is that it allows the dendritic arbor to explore a larger portion of the neuropile than in normal animals. In fact, we observe that in Cha mutants, the dendritic arbor of aCC extends into regions of the neuropile that are not normally invaded in control conditions (Figure 2C, arrowhead). This change in the dendritic distribution is also confirmed by the shift of the peak in the Sholl analysis (Figure 2F).

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