Auditory cortex shapes sound responses in the inferior colliculus
- University of Pennsylvania, United States
Abstract
The extensive feedback from the auditory cortex (AC) to the inferior colliculus (IC) supports critical aspects of auditory behavior but has not been extensively characterized. Previous studies demonstrated that activity in IC is altered by focal electrical stimulation and pharmacological inactivation of AC, but these methods lack the ability to selectively manipulate projection neurons. We measured the effects of selective optogenetic modulation of cortico-collicular feedback projections on IC sound responses in mice. Activation of feedback increased spontaneous activity and decreased stimulus selectivity in IC, whereas suppression had no effect. To further understand how microcircuits in AC may control collicular activity, we optogenetically modulated different cortical neuronal subtypes, specifically parvalbumin-positive (PV) and somatostatin-positive (SST) inhibitory interneurons. We found that modulating either type of interneuron did not affect IC sound-evoked activity. Combined, our results identify that activation of excitatory projections, but not inhibition-driven changes in cortical activity, affects collicular sound responses.
Data availability
Original spike data and code are available on Dryad (doi:10.5061/dryad.1t61c80).
Article and author information
Author details
Funding
National Institute on Deafness and Other Communication Disorders (R03DC013660)
- Maria N Geffen
National Institute on Deafness and Other Communication Disorders (NIH R01DC014779)
- Maria N Geffen
National Institute on Deafness and Other Communication Disorders (NIH R01DC015527)
- Maria N Geffen
Klingenstein Award in Neurosciences
- Maria N Geffen
Human Frontier in Science
- Maria N Geffen
Pennsylvania Lions Club Hearing Research Fellowship
- Maria N Geffen
National Institute on Deafness and Other Communication Disorders (1F32MH120890)
- Alexandria MH Lesicko
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Catherine Emily Carr, University of Maryland, United States
Ethics
Animal experimentation: All animal work was conducted according to the guidelines of University of Pennsylvanian IACUC (protocol number 803266) and the AALAC Guide on Animal Research. Anesthesia by isoflurane and ketamine and euthanasia by CO2 were used. All means were taken to minimize the pain or discomfort of the animals during and following the experiments. All experiments were performed during the animals' dark cycle.
Version history
- Received: September 15, 2019
- Accepted: January 31, 2020
- Accepted Manuscript published: January 31, 2020 (version 1)
- Version of Record published: March 9, 2020 (version 2)
Copyright
© 2020, Blackwell 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
-
- 3,769
- views
-
- 609
- downloads
-
- 45
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
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)
Auditory cortex shapes sound responses in the inferior colliculus
eLife 9:e51890.
https://doi.org/10.7554/eLife.51890
Further reading
-
- Genetics and Genomics
- Neuroscience
Single-cell RNA sequencing reveals the extent to which marmosets carry genetically distinct cells from their siblings.
-
- Cell Biology
- Neuroscience
Mutations in Drosophila Swiss Cheese (SWS) gene or its vertebrate orthologue Neuropathy Target Esterase (NTE) lead to progressive neuronal degeneration in flies and humans. Despite its enzymatic function as a phospholipase is well-established, the molecular mechanism responsible for maintaining nervous system integrity remains unclear. In this study, we found that NTE/SWS is present in surface glia that forms the blood-brain-barrier (BBB) and that NTE/SWS is important to maintain its structure and permeability. Importantly, BBB glia-specific expression of Drosophila NTE/SWS or human NTE in the sws mutant background fully rescues surface glial organization and partially restores BBB integrity, suggesting a conserved function of NTE/SWS. Interestingly, sws mutant glia showed abnormal organization of plasma membrane domains and tight junction rafts accompanied by the accumulation of lipid droplets, lysosomes, and multilamellar bodies. Since the observed cellular phenotypes closely resemble the characteristics described in a group of metabolic disorders known as lysosomal storage diseases (LSDs), our data established a novel connection between NTE/SWS and these conditions. We found that mutants with defective BBB exhibit elevated levels of fatty acids, which are precursors of eicosanoids and are involved in the inflammatory response. Also, as a consequence of a permeable BBB, several innate immunity factors are upregulated in an age-dependent manner, while BBB glia-specific expression of NTE/SWS normalizes inflammatory response. Treatment with anti-inflammatory agents prevents the abnormal architecture of the BBB, suggesting that inflammation contributes to the maintenance of a healthy brain barrier. Considering the link between a malfunctioning BBB and various neurodegenerative diseases, gaining a deeper understanding of the molecular mechanisms causing inflammation due to a defective BBB could help to promote the use of anti-inflammatory therapies for age-related neurodegeneration.
