Synergistic plasticity of intrinsic conductance and electrical coupling restores synchrony in an intact motor network
Abstract
Motor neurons of the crustacean cardiac ganglion generate virtually identical, synchronized output despite the fact that each neuron uses distinct conductance magnitudes. As a result of this variability, manipulations that target ionic conductances have distinct effects on neurons within the same ganglion, disrupting synchronized motor neuron output that is necessary for proper cardiac function. We hypothesized that robustness in network output is accomplished via plasticity that counters such destabilizing influences. By blocking high-threshold K+ conductances in motor neurons within the ongoing cardiac network, we discovered that compensation both resynchronized the network and helped restore excitability. Using model findings to guide experimentation, we determined that compensatory increases of both GA and electrical coupling restored function in the network. This is one of the first direct demonstrations of physiological regulation of coupling conductance in a compensatory context, and of synergistic plasticity across cell- and network-level mechanisms in the restoration of output.
Article and author information
Author details
Funding
National Institutes of Health (MH46742)
- David J Schulz
University of Missouri Research Board
- Satish S Nair
- David J Schulz
National Institutes of Health (MH087755)
- Satish S Nair
National Institutes of Health (5T32GM008396)
- Brian J Lane
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2016, Lane et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 891
- views
-
- 221
- downloads
-
- 30
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
When subjects navigate through spatial environments, grid cells exhibit firing fields that are arranged in a triangular grid pattern. Direct recordings of grid cells from the human brain are rare. Hence, functional magnetic resonance imaging (fMRI) studies proposed an indirect measure of entorhinal grid-cell activity, quantified as hexadirectional modulation of fMRI activity as a function of the subject’s movement direction. However, it remains unclear how the activity of a population of grid cells may exhibit hexadirectional modulation. Here, we use numerical simulations and analytical calculations to suggest that this hexadirectional modulation is best explained by head-direction tuning aligned to the grid axes, whereas it is not clearly supported by a bias of grid cells toward a particular phase offset. Firing-rate adaptation can result in hexadirectional modulation, but the available cellular data is insufficient to clearly support or refute this option. The magnitude of hexadirectional modulation furthermore depends considerably on the subject’s navigation pattern, indicating that future fMRI studies could be designed to test which hypothesis most likely accounts for the fMRI measure of grid cells. Our findings also underline the importance of quantifying the properties of human grid cells to further elucidate how hexadirectional modulations of fMRI activity may emerge.
-
- Developmental Biology
- Neuroscience
Environmental insults, including mild head trauma, significantly increase the risk of neurodegeneration. However, it remains challenging to establish a causative connection between early-life exposure to mild head trauma and late-life emergence of neurodegenerative deficits, nor do we know how sex and age compound the outcome. Using a Drosophila model, we demonstrate that exposure to mild head trauma causes neurodegenerative conditions that emerge late in life and disproportionately affect females. Increasing age-at-injury further exacerbates this effect in a sexually dimorphic manner. We further identify sex peptide signaling as a key factor in female susceptibility to post-injury brain deficits. RNA sequencing highlights a reduction in innate immune defense transcripts specifically in mated females during late life. Our findings establish a causal relationship between early head trauma and late-life neurodegeneration, emphasizing sex differences in injury response and the impact of age-at-injury. Finally, our findings reveal that reproductive signaling adversely impacts female response to mild head insults and elevates vulnerability to late-life neurodegeneration.