Variation of connectivity across exemplar sensory and associative thalamocortical loops in the mouse

  1. Arghya Mukherjee  Is a corresponding author
  2. Navdeep Bajwa
  3. Norman H Lam
  4. César Porrero
  5. Francisco Clasca
  6. Michael M Halassa  Is a corresponding author
  1. Massachusetts Institute of Technology, United States
  2. Autonoma University of Madrid, Spain

Abstract

The thalamus engages in sensation, action, and cognition, but the structure underlying these functions is poorly understood. Thalamic innervation of associative cortex targets several interneuron types, modulating dynamics and influencing plasticity. Is this structure-function relationship distinct from that of sensory thalamocortical systems? Here, we systematically compared function and structure across a sensory and an associative thalamocortical loop in the mouse. Enhancing excitability of mediodorsal thalamus, an associative structure, resulted in prefrontal activity dominated by inhibition. Equivalent enhancement of medial geniculate excitability robustly drove auditory cortical excitation. Structurally, geniculate axons innervated excitatory cortical targets in a preferential manner and with larger synaptic terminals, providing a putative explanation for functional divergence. The two thalamic circuits also had distinct input patterns, with mediodorsal thalamus receiving innervation from a diverse set of cortical areas. Altogether, our findings contribute to the emerging view of functional diversity across thalamic microcircuits and its structural basis.

Data availability

All data generated or analyzed are included in the manuscript as source data files for Figures 1 to 7.

Article and author information

Author details

  1. Arghya Mukherjee

    Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, United States
    For correspondence
    mukhargh@mit.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3341-4408
  2. Navdeep Bajwa

    Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Norman H Lam

    Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. César Porrero

    Anatomy and Neuroscience, Autonoma University of Madrid, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Francisco Clasca

    Anatomy and Neuroscience, Autonoma University of Madrid, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0718-1337
  6. Michael M Halassa

    Neuroscience Institute, Massachusetts Institute of Technology, New York, United States
    For correspondence
    mhalassa@mit.edu
    Competing interests
    The authors declare that no competing interests exist.

Funding

European Commission (945539-HBP-SGA3)

  • Francisco Clasca

National Institute of Mental Health (R01MH120118)

  • Michael M Halassa

National Institute of Mental Health (R01MH107680)

  • Michael M Halassa

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Mathieu Wolff, CNRS, University of Bordeaux, France

Ethics

Animal experimentation: All animal experiments were performed according to the guidelines of the US National Institutes of Health and the Institutional Animal Care and Use Committee at the Massachusetts Institute of Technology. Experimental procedures for bouton analysis as shown in figure 4 were approved by the Autonoma de Madrid University ethics committee and the corresponding Madrid Regional Government agency (PROEX175/16), in accordance with the European Community Council Directive 2010/63/UE.

Version history

  1. Received: August 28, 2020
  2. Accepted: October 23, 2020
  3. Accepted Manuscript published: October 26, 2020 (version 1)
  4. Version of Record published: November 5, 2020 (version 2)

Copyright

© 2020, Mukherjee 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

  • 3,809
    views
  • 533
    downloads
  • 27
    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)

  1. Arghya Mukherjee
  2. Navdeep Bajwa
  3. Norman H Lam
  4. César Porrero
  5. Francisco Clasca
  6. Michael M Halassa
(2020)
Variation of connectivity across exemplar sensory and associative thalamocortical loops in the mouse
eLife 9:e62554.
https://doi.org/10.7554/eLife.62554

Share this article

https://doi.org/10.7554/eLife.62554

Further reading

    1. Neuroscience
    Ya-Hui Lin, Li-Wen Wang ... Li-An Chu
    Research Article

    Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

    1. Neuroscience
    Amanda Chu, Nicholas T Gordon ... Michael A McDannald
    Research Article

    Pavlovian fear conditioning has been extensively used to study the behavioral and neural basis of defensive systems. In a typical procedure, a cue is paired with foot shock, and subsequent cue presentation elicits freezing, a behavior theoretically linked to predator detection. Studies have since shown a fear conditioned cue can elicit locomotion, a behavior that - in addition to jumping, and rearing - is theoretically linked to imminent or occurring predation. A criticism of studies observing fear conditioned cue-elicited locomotion is that responding is non-associative. We gave rats Pavlovian fear discrimination over a baseline of reward seeking. TTL-triggered cameras captured 5 behavior frames/s around cue presentation. Experiment 1 examined the emergence of danger-specific behaviors over fear acquisition. Experiment 2 examined the expression of danger-specific behaviors in fear extinction. In total, we scored 112,000 frames for nine discrete behavior categories. Temporal ethograms show that during acquisition, a fear conditioned cue suppresses reward seeking and elicits freezing, but also elicits locomotion, jumping, and rearing - all of which are maximal when foot shock is imminent. During extinction, a fear conditioned cue most prominently suppresses reward seeking, and elicits locomotion that is timed to shock delivery. The independent expression of these behaviors in both experiments reveal a fear conditioned cue to orchestrate a temporally organized suite of behaviors.