Convergence of inputs from the basal ganglia with layer 5 of motor cortex and cerebellum in mouse motor thalamus

  1. Kevin P Koster
  2. S Murray Sherman  Is a corresponding author
  1. University of Chicago, United States

Abstract

A key to motor control is the motor thalamus, where several inputs converge. One excitatory input originates from layer 5 of primary motor cortex (M1L5), while another arises from the deep cerebellar nuclei (Cb). M1L5 terminals distribute throughout the motor thalamus and overlap with GABAergic inputs from the basal ganglia output nuclei, the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr). In contrast, it is thought that Cb and basal ganglia inputs are segregated. Therefore, we hypothesized that one potential function of the GABAergic inputs from basal ganglia is to selectively inhibit, or gate, excitatory signals from M1L5 in the motor thalamus. Here, we tested this possibility and determined the circuit organization of mouse (both sexes) motor thalamus using an optogenetic strategy in acute slices. First, we demonstrated the presence of a feedforward transthalamic pathway from M1L5 through motor thalamus. Importantly, we discovered that GABAergic inputs from the GPi and SNr converge onto single motor thalamic cells with excitatory synapses from M1L5. Separately, we also demonstrate that, perhaps unexpectedly, GABAergic GPi and SNr inputs converge with those from the Cb. We interpret these results to indicate that a role of the basal ganglia is to gate the thalamic transmission of M1L5 and Cb information to cortex.

Data availability

All data generated or analyzed during this study are represented in the Figures. Mean values and sample variability are listed in the Results section of the text where applicable. Individual data points are represented on the graphs/Figures. In addition, source data files for all quantitate data are provided.

Article and author information

Author details

  1. Kevin P Koster

    Department of Neurobiology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2935-3427
  2. S Murray Sherman

    Department of Neurobiology, University of Chicago, Chicago, United States
    For correspondence
    msherman@bsd.uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1520-2778

Funding

National Institute of Neurological Disorders and Stroke (NS094184)

  • S Murray Sherman

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

Reviewing Editor

  1. Eunji Cheong, Yonsei University, Republic of Korea

Ethics

Animal experimentation: All experiments were performed in accordance with protocols approved by the Institutional Animal Care and Use Committee at the University of Chicago.

Version history

  1. Received: March 1, 2024
  2. Accepted: June 6, 2024
  3. Accepted Manuscript published: June 10, 2024 (version 1)

Copyright

© 2024, Koster & Sherman

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

  • 180
    views
  • 75
    downloads
  • 0
    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. Kevin P Koster
  2. S Murray Sherman
(2024)
Convergence of inputs from the basal ganglia with layer 5 of motor cortex and cerebellum in mouse motor thalamus
eLife 13:e97489.
https://doi.org/10.7554/eLife.97489

Share this article

https://doi.org/10.7554/eLife.97489

Further reading

    1. Neuroscience
    Ece Kaya, Sonja A Kotz, Molly J Henry
    Research Article

    Dynamic attending theory proposes that the ability to track temporal cues in the auditory environment is governed by entrainment, the synchronization between internal oscillations and regularities in external auditory signals. Here, we focused on two key properties of internal oscillators: their preferred rate, the default rate in the absence of any input; and their flexibility, how they adapt to changes in rhythmic context. We developed methods to estimate oscillator properties (Experiment 1) and compared the estimates across tasks and individuals (Experiment 2). Preferred rates, estimated as the stimulus rates with peak performance, showed a harmonic relationship across measurements and were correlated with individuals’ spontaneous motor tempo. Estimates from motor tasks were slower than those from the perceptual task, and the degree of slowing was consistent for each individual. Task performance decreased with trial-to-trial changes in stimulus rate, and responses on individual trials were biased toward the preceding trial’s stimulus properties. Flexibility, quantified as an individual’s ability to adapt to faster-than-previous rates, decreased with age. These findings show domain-specific rate preferences for the assumed oscillatory system underlying rhythm perception and production, and that this system loses its ability to flexibly adapt to changes in the external rhythmic context during aging.

    1. Neuroscience
    Elissavet Chartampila, Karim S Elayouby ... Helen E Scharfman
    Research Article

    Maternal choline supplementation (MCS) improves cognition in Alzheimer’s disease (AD) models. However, the effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated the effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse. The most common type of hyperexcitability in Tg2576 mice are generalized EEG spikes (interictal spikes [IIS]). IIS also are common in other mouse models and occur in AD patients. In mouse models, hyperexcitability is also reflected by elevated expression of the transcription factor ∆FosB in the granule cells (GCs) of the dentate gyrus (DG), which are the principal cell type. Therefore, we studied ΔFosB expression in GCs. We also studied the neuronal marker NeuN within hilar neurons of the DG because reduced NeuN protein expression is a sign of oxidative stress or other pathology. This is potentially important because hilar neurons regulate GC excitability. Tg2576 breeding pairs received a diet with a relatively low, intermediate, or high concentration of choline. After weaning, all mice received the intermediate diet. In offspring of mice fed the high choline diet, IIS frequency declined, GC ∆FosB expression was reduced, and hilar NeuN expression was restored. Using the novel object location task, spatial memory improved. In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB protein expression. However, their IIS frequency was low, which was surprising. The results provide new evidence that a diet high in choline in early life can improve outcomes in a mouse model of AD, and relatively low choline can have mixed effects. This is the first study showing that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB, and spatial memory in an animal model of AD.