Structural Homeostasis: Compensatory Adjustments of Dendritic Arbor Geometry in Response to Variations of Synaptic Input

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.

Longitudinal in vivo Imaging Reveals Balanced and Branch-Specific Remodeling of Mature Cortical Pyramidal Dendritic Arbors after Stroke

“…The fact that total dendritic length within individual neurons did not change significantly over time, despite a threefold increase in dendrite remodeling, suggests that mature cortical neurons may possess an intrinsic mechanism that conserves the total amount of space each neuron occupies. Although this type of homeostasis has been postulated in previous studies that measured dendritic features in Drosophila embryos (Tripodi et al, 2008) and postmortem sections of the hippocampus (Samsonovich and Ascoli, 2006), our data are the first to directly visualize this phenomenon within individual neurons in vivo. Exactly what molecular mechanisms could account for this type of plasticity remain unclear.…”

Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons

“…However, other authors have suggested that the arrival of a presynaptic input could act as a stop-growth or stabilization signal for the postsynaptic dendritic arbor. This sprouting would allow the brain to compensate for low network activity (33) and might be an attempt by the brain to adapt (recovering or sparing) to function loss (34). If this were the case, then a more complex dendritic organization should be associated with a loss of memory, and a less developed dendritic organization should be associated with a gain of function.…”

Tiling among stereotyped dendritic branches in an identified Drosophila motoneuron

“…This is not surprising because three independent studies have demonstrated that Drosophila motoneuron dendritic branching is affected by neural activity (Hartwig et al, 2008;Duch et al, 2008;Tripodi et al, 2008). By contrast, the mean dendritic radius and the mean length of the individual segments show high constancy between animals (CV < 0.08).…”

“…Analyses of the dendritic branching patterns of sensory neurons paired with genetic screens and manipulations have already yielded fundamental insight into key regulatory mechanisms of dendrite development (Grueber and Jan, 2004;Corty et al, 2009). However, much less is known about the specific architecture principles and the constancy of the complex dendritic trees of identified central Drosophila neurons, although these exhibit stereotyped morphologies and have proven useful for analyzing mechanisms of dendritic morphogenesis in the central nervous system (CNS) (Williams and Truman, 2005;Landgraf and Thor, 2006;Tripodi et al, 2008;Hartwig et al, 2008).…”

“…Self-avoidance alone would explain why dendrites of MN5 evenly cover the input space and barely overlap, but it would not explain why dendrites within one subtree come much closer to each other than dendrites from neighboring subtrees, so that neighboring subtrees do not interdigitate with each other. However, a recent study on embryonic Drosophila motoneurons has shown that synaptic input to developing dendrites facilitates stabilization of individual dendrites and also of nonsynaptic neighbor dendrites on the same subtree (Tripodi et al, 2008). If these mechanisms also affected adult Drosophila motoneuron dendritic growth, activity-dependent stabilization of subtrees that receive synaptic input first paired with self-avoidance mechanisms between all dendrites of MN5 could cause the observed spatial separation of MN5 dendritic subtrees.…”