Laser ablation of Dbx1 neurons in the pre-Bötzinger Complex stops inspiratory rhythm and impairs output in neonatal mice
Abstract
To understand the neural origins of rhythmic behavior one must characterize the central pattern generator circuit and quantify the population size needed to sustain functionality. Breathing-related interneurons of the brainstem pre-Bötzinger complex (preBötC) that putatively comprise the core respiratory rhythm generator in mammals are derived from Dbx1-expressing precursors. Here we show that selective photonic destruction of Dbx1 preBötC neurons in neonatal mouse slices impairs respiratory rhythm but surprisingly also the magnitude of motor output; respiratory hypoglossal nerve discharge decreased and its frequency steadily diminished until rhythm stopped irreversibly after 85±20 (mean ± SEM) cellular ablations, which corresponds to ~15% of the estimated population. These results demonstrate that a single canonical interneuron class generates respiratory rhythm and contributes in a premotor capacity, whereas these functions are normally attributed to discrete populations. We also establish quantitative cellular parameters that govern network viability, which may have ramifications for respiratory pathology in disease states.
Article and author information
Author details
Ethics
Animal experimentation: The Institutional Animal Care and Use Committee (IACUC) at The College of William & Mary, which ensures compliance with United States federal regulations concerning care and use of vertebrate animals in research, approved the following protocols (IACUC-2013-07-10-8828-cadeln). The anesthesia and surgery protocols are consistent with the 2011 guidelines of the Animal Research Advisory Committee, which is part of the Office of Animal Care and Use of the National Institutes of Health of the USA.
Copyright
© 2014, Wang 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
-
- 2,562
- views
-
- 938
- downloads
-
- 84
- 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
The gonadotropin-releasing hormone (GnRH) neurons represent the key output cells of the neural network controlling mammalian fertility. We used GCaMP fiber photometry to record the population activity of the GnRH neuron distal projections in the ventral arcuate nucleus where they merge before entering the median eminence to release GnRH into the portal vasculature. Recordings in freely behaving intact male and female mice revealed abrupt ~8 min duration increases in activity that correlated perfectly with the appearance of a subsequent pulse of luteinizing hormone (LH). The GnRH neuron dendrons also exhibited a low level of unchanging clustered, rapidly fluctuating baseline activity in males and throughout the estrous cycle in females. In female mice, a gradual increase in basal activity that exhibited ~80 min oscillations began in the afternoon of proestrus and lasted for 12 hr. This was associated with the onset of the LH surge that ended several hours before the fall in the GCaMP signal. Abrupt 8 min duration episodes of GCaMP activity continued to occur on top of the rising surge baseline before ceasing in estrus. These observations provide the first description of GnRH neuron activity in freely behaving animals. They demonstrate that three distinct patterns of oscillatory activity occur in GnRH neurons. These are comprised of low-level rapid baseline activity, abrupt 8 min duration oscillations that drive pulsatile gonadotropin secretion, and, in females, a gradual and very prolonged oscillating increase in activity responsible for the preovulatory LH surge.
-
- Neuroscience
- Physics of Living Systems
Recent experimental studies showed that electrically coupled neural networks like in mammalian inferior olive nucleus generate synchronized rhythmic activity by the subthreshold sinusoidal-like oscillations of the membrane voltage. Understanding the basic mechanism and its implication of such phenomena in the nervous system bears fundamental importance and requires preemptively the connectome information of a given nervous system. Inspired by these necessities of developing a theoretical and computational model to this end and, however, in the absence of connectome information for the inferior olive nucleus, here we investigated interference phenomena of the subthreshold oscillations in the reference system Caenorhabditis elegans for which the structural anatomical connectome was completely known recently. We evaluated how strongly the sinusoidal wave was transmitted between arbitrary two cells in the model network. The region of cell-pairs that are good at transmitting waves changed according to the wavenumber of the wave, for which we named a wavenumber-dependent transmission map. Also, we unraveled that (1) the transmission of all cell-pairs disappeared beyond a threshold wavenumber, (2) long distance and regular patterned transmission existed in the body-wall muscles part of the model network, and (3) major hub cell-pairs of the transmission were identified for many wavenumber conditions. A theoretical and computational model presented in this study provided fundamental insight for understanding how the multi-path constructive/destructive interference of the subthreshold oscillations propagating on electrically coupled neural networks could generate wavenumber-dependent synchronized rhythmic activity.