Revealing the distribution of transmembrane currents along the dendritic tree of a neuron from extracellular recordings
Abstract
Revealing the current source distribution along the neuronal membrane is a key step on the way to understanding neural computations, however, the experimental and theoretical tools to achieve sufficient spatiotemporal resolution for the estimation remain to be established. Here we address this problem using extracellularly recorded potentials with arbitrarily distributed electrodes for a neuron of known morphology. We use simulations of models with varying complexity to validate the proposed method and to give recommendations for experimental applications. The method is applied to in vitro data from rat hippocampus.
Data availability
-
Neuron morphology Badea2011Fig2DuPublicly available at NeuroMorpho.Org (ID : NMO_10743).
Article and author information
Author details
Funding
Ministerstwo Nauki i Szkolnictwa Wyższego (Grant 2729/7.PR/2013/2)
- Daniel K Wojcik
Nemzeti Kutatási, Fejlesztesi és Innovacios Hivatal (Grant K 113147)
- Zoltán Somogyvári
Nemzeti Agykutatasi Program (Grant KTIA NAP 13-1-2013-0001)
- István Ulbert
Nemzeti Kutatasi, Fejilesztesi es Innovacios Hivatal (Grant NN 118902)
- Zoltán Somogyvári
Nemzeti Agykutatasi Program (Grant KTIA-13-NAP-A-IV/1 2 3 4 6)
- István Ulbert
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: The in vitro experiment was performed according to the EC Council Directive of November 24, 1986 (86/89/EEC) and all procedures were reviewed and approved by the local ethical committee and the Hungarian Central Government Office (license number: PEI/001/695-9/2015).
Reviewing Editor
- Frances K Skinner, Krembil Research Institute, University Health Network, Canada
Publication history
- Received: June 7, 2017
- Accepted: November 16, 2017
- Accepted Manuscript published: November 17, 2017 (version 1)
- Version of Record published: December 5, 2017 (version 2)
- Version of Record updated: December 5, 2017 (version 3)
- Version of Record updated: February 20, 2018 (version 4)
Copyright
© 2017, Cserpán 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
-
- 1,965
- Page views
-
- 369
- Downloads
-
- 7
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
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
-
- Cell Biology
- Neuroscience
Caenorhabditis elegans neurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a mechanism for stressed neurons to eject toxic protein aggregates and organelles. However, little is known of the fate of the exopher once it leaves the neuron. We found that exophers produced by mechanosensory neurons in C. elegans are engulfed by surrounding hypodermal skin cells and are then broken up into numerous smaller vesicles that acquire hypodermal phagosome maturation markers, with vesicular contents gradually degraded by hypodermal lysosomes. Consistent with the hypodermis acting as an exopher phagocyte, we found that exopher removal requires hypodermal actin and Arp2/3, and the hypodermal plasma membrane adjacent to newly formed exophers accumulates dynamic F-actin during budding. Efficient fission of engulfed exopher-phagosomes to produce smaller vesicles and degrade their contents requires phagosome maturation factors SAND-1/Mon1, GTPase RAB-35, the CNT-1 ARF-GAP, and microtubule motor-associated GTPase ARL-8, suggesting a close coupling of phagosome fission and phagosome maturation. Lysosome activity was required to degrade exopher contents in the hypodermis but not for exopher-phagosome resolution into smaller vesicles. Importantly, we found that GTPase ARF-6 and effector SEC-10/exocyst activity in the hypodermis, along with the CED-1 phagocytic receptor, is required for efficient production of exophers by the neuron. Our results indicate that the neuron requires specific interaction with the phagocyte for an efficient exopher response, a mechanistic feature potentially conserved with mammalian exophergenesis, and similar to neuronal pruning by phagocytic glia that influences neurodegenerative disease.
-
- Neuroscience
The axonal guidance cue netrin-1 serves a critical role in neural circuit development by promoting growth cone motility, axonal branching, and synaptogenesis. Within the adult mouse brain, expression of the gene encoding (Ntn1) is highly enriched in the ventral midbrain where it is expressed in both GABAergic and dopaminergic neurons, but its function in these cell types in the adult system remains largely unknown. To address this, we performed viral-mediated, cell-type specific CRISPR-Cas9 mutagenesis of Ntn1 in the ventral tegmental area (VTA) of adult mice. Ntn1 loss-of-function in either cell type resulted in a significant reduction in excitatory postsynaptic connectivity. In dopamine neurons, the reduced excitatory tone had a minimal phenotypic behavioral outcome; however, reduced glutamatergic tone on VTA GABA neurons induced behaviors associated with a hyperdopaminergic phenotype. Simultaneous loss of Ntn1 function in both cell types largely rescued the phenotype observed in the GABA-only mutagenesis. These findings demonstrate an important role for Ntn1 in maintaining excitatory connectivity in the adult midbrain and that a balance in this connectivity within two of the major cell types of the VTA is critical for the proper functioning of the mesolimbic system.