Limits...
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.

Show MeSH

Related in: MedlinePlus

Development of the aCC Dendritic Arbor(A) Diagram of the ventral nerve cord (VNC) of a Drosophila embryo. The aCC is depicted in green, and two putative presynaptic cholinergic interneurons in blue and magenta. FasII-positive axon bundles are in grey, positioned in the lateral, intermediate, and medial neuropile. Note that this diagram illustrates a hypothetical pattern of connections. The actual number of interneurons presynaptic to motor neurons is currently unknown.(B) A 3-D projection of a confocal stack of an 18-h aCC (pseudocoloured green) in the context of the FasII-positive fascicles (grey). The box outlines the main (ipsilateral) dendritic arbor shown in the reconstructions below (C–E). Scale bar indicates 5 μm.(C–E) Reconstructions of aCC ipsilateral dendritic arbors at 14 h, 16 h, and 18 h AEL, respectively. Reconstructions are based on confocal image stacks of aCC neurons labelled by intracellular Lucifer Yellow injections. The dendrites are pseudocoloured yellow, and the axon/primary neurite, from which dendrites grow out, blue. For improved clarity, the cell body, located at the lower end of the axon, has been omitted from the reconstructions. Scale bar indicates 5 μm.(F) Growth curve of the aCC dendritic arbor: the y-axis indicates total tree length in μm; the x-axis indicates developmental stage in hours after egg laying (AEL). The dotted line shows a regression analysis calculated exclusively from data of early stages 14–16 h AEL. The resultant R2 value is plotted above. The graph for 17 and 18 h AEL is an extrapolation at the growth rate calculated for earlier stages 14–16 h AEL. Times of onset of electrical properties of aCC are indicated [16]. Error bars indicate SEM.Anterior is left, and arrowheads indicate the ventral midline.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2573934&req=5

pbio-0060260-g001: Development of the aCC Dendritic Arbor(A) Diagram of the ventral nerve cord (VNC) of a Drosophila embryo. The aCC is depicted in green, and two putative presynaptic cholinergic interneurons in blue and magenta. FasII-positive axon bundles are in grey, positioned in the lateral, intermediate, and medial neuropile. Note that this diagram illustrates a hypothetical pattern of connections. The actual number of interneurons presynaptic to motor neurons is currently unknown.(B) A 3-D projection of a confocal stack of an 18-h aCC (pseudocoloured green) in the context of the FasII-positive fascicles (grey). The box outlines the main (ipsilateral) dendritic arbor shown in the reconstructions below (C–E). Scale bar indicates 5 μm.(C–E) Reconstructions of aCC ipsilateral dendritic arbors at 14 h, 16 h, and 18 h AEL, respectively. Reconstructions are based on confocal image stacks of aCC neurons labelled by intracellular Lucifer Yellow injections. The dendrites are pseudocoloured yellow, and the axon/primary neurite, from which dendrites grow out, blue. For improved clarity, the cell body, located at the lower end of the axon, has been omitted from the reconstructions. Scale bar indicates 5 μm.(F) Growth curve of the aCC dendritic arbor: the y-axis indicates total tree length in μm; the x-axis indicates developmental stage in hours after egg laying (AEL). The dotted line shows a regression analysis calculated exclusively from data of early stages 14–16 h AEL. The resultant R2 value is plotted above. The graph for 17 and 18 h AEL is an extrapolation at the growth rate calculated for earlier stages 14–16 h AEL. Times of onset of electrical properties of aCC are indicated [16]. Error bars indicate SEM.Anterior is left, and arrowheads indicate the ventral midline.

Mentions: From 14–16 h AEL, the length of the dendritic arbor increases linearly with an average growth rate of 23 ± 2 μm per hour (tree length at 14 h: 45 ± 7 μm, n = 8; 15 h: 69 ± 3 μm, n = 9; and 16 h: 90 ± 5 μm, n = 11) (Figure 1C–1F). Between 16 and 18 h AEL, growth diverges from a linear increase as the average extension rate decreases by about 43% (13 ± 4 μm per hour; tree length at 17 h: 99 ± 8 μm, n = 8; and 18 h: 115 ± 7 μm, n = 13) (Figure 1D). Interestingly, 16 h AEL is the first stage at which evoked postsynaptic currents (EPSCs) can be recorded from aCC [16]. It seemed therefore possible that the onset of electrical activity might be the cause of the reduced rate of dendritic growth as of 16 h AEL, and we decided to investigate this further.


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)

Development of the aCC Dendritic Arbor(A) Diagram of the ventral nerve cord (VNC) of a Drosophila embryo. The aCC is depicted in green, and two putative presynaptic cholinergic interneurons in blue and magenta. FasII-positive axon bundles are in grey, positioned in the lateral, intermediate, and medial neuropile. Note that this diagram illustrates a hypothetical pattern of connections. The actual number of interneurons presynaptic to motor neurons is currently unknown.(B) A 3-D projection of a confocal stack of an 18-h aCC (pseudocoloured green) in the context of the FasII-positive fascicles (grey). The box outlines the main (ipsilateral) dendritic arbor shown in the reconstructions below (C–E). Scale bar indicates 5 μm.(C–E) Reconstructions of aCC ipsilateral dendritic arbors at 14 h, 16 h, and 18 h AEL, respectively. Reconstructions are based on confocal image stacks of aCC neurons labelled by intracellular Lucifer Yellow injections. The dendrites are pseudocoloured yellow, and the axon/primary neurite, from which dendrites grow out, blue. For improved clarity, the cell body, located at the lower end of the axon, has been omitted from the reconstructions. Scale bar indicates 5 μm.(F) Growth curve of the aCC dendritic arbor: the y-axis indicates total tree length in μm; the x-axis indicates developmental stage in hours after egg laying (AEL). The dotted line shows a regression analysis calculated exclusively from data of early stages 14–16 h AEL. The resultant R2 value is plotted above. The graph for 17 and 18 h AEL is an extrapolation at the growth rate calculated for earlier stages 14–16 h AEL. Times of onset of electrical properties of aCC are indicated [16]. Error bars indicate SEM.Anterior is left, and arrowheads indicate the ventral midline.
© Copyright Policy
Related In: Results  -  Collection

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

pbio-0060260-g001: Development of the aCC Dendritic Arbor(A) Diagram of the ventral nerve cord (VNC) of a Drosophila embryo. The aCC is depicted in green, and two putative presynaptic cholinergic interneurons in blue and magenta. FasII-positive axon bundles are in grey, positioned in the lateral, intermediate, and medial neuropile. Note that this diagram illustrates a hypothetical pattern of connections. The actual number of interneurons presynaptic to motor neurons is currently unknown.(B) A 3-D projection of a confocal stack of an 18-h aCC (pseudocoloured green) in the context of the FasII-positive fascicles (grey). The box outlines the main (ipsilateral) dendritic arbor shown in the reconstructions below (C–E). Scale bar indicates 5 μm.(C–E) Reconstructions of aCC ipsilateral dendritic arbors at 14 h, 16 h, and 18 h AEL, respectively. Reconstructions are based on confocal image stacks of aCC neurons labelled by intracellular Lucifer Yellow injections. The dendrites are pseudocoloured yellow, and the axon/primary neurite, from which dendrites grow out, blue. For improved clarity, the cell body, located at the lower end of the axon, has been omitted from the reconstructions. Scale bar indicates 5 μm.(F) Growth curve of the aCC dendritic arbor: the y-axis indicates total tree length in μm; the x-axis indicates developmental stage in hours after egg laying (AEL). The dotted line shows a regression analysis calculated exclusively from data of early stages 14–16 h AEL. The resultant R2 value is plotted above. The graph for 17 and 18 h AEL is an extrapolation at the growth rate calculated for earlier stages 14–16 h AEL. Times of onset of electrical properties of aCC are indicated [16]. Error bars indicate SEM.Anterior is left, and arrowheads indicate the ventral midline.
Mentions: From 14–16 h AEL, the length of the dendritic arbor increases linearly with an average growth rate of 23 ± 2 μm per hour (tree length at 14 h: 45 ± 7 μm, n = 8; 15 h: 69 ± 3 μm, n = 9; and 16 h: 90 ± 5 μm, n = 11) (Figure 1C–1F). Between 16 and 18 h AEL, growth diverges from a linear increase as the average extension rate decreases by about 43% (13 ± 4 μm per hour; tree length at 17 h: 99 ± 8 μm, n = 8; and 18 h: 115 ± 7 μm, n = 13) (Figure 1D). Interestingly, 16 h AEL is the first stage at which evoked postsynaptic currents (EPSCs) can be recorded from aCC [16]. It seemed therefore possible that the onset of electrical activity might be the cause of the reduced rate of dendritic growth as of 16 h AEL, and we decided to investigate this further.

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