Laminar-specific cortico-cortical loops in mouse visual cortex
- Champalimaud Center for the Unknown, Portugal
Abstract
Many theories propose recurrent interactions across the cortical hierarchy, but it is unclear if cortical circuits are selectively wired to implement looped computations. Using subcellular channelrhodopsin-2-assisted circuit mapping in mouse visual cortex, we compared feedforward (FF) or feedback (FB) cortico-cortical synaptic input to cells projecting back to the input source (looped neurons) with cells projecting to a different cortical or subcortical area. FF and FB afferents showed similar cell-type selectivity, making stronger connections with looped neurons than with other projection types in layer (L) 5 and L6, but not in L2/3, resulting in selective modulation of activity in looped neurons. In most cases, stronger connections in looped L5 neurons were located on their apical tufts, but not on their perisomatic dendrites. Our results reveal that cortico-cortical connections are selectively wired to form monosynaptic excitatory loops and support a differential role of supragranular and infragranular neurons in hierarchical recurrent computations.
Data availability
All data is publicly available on Dryad https://doi.org/10.5061/dryad.1ns1rn8r7
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Laminar-specific cortico-cortical loops in mouse visual cortexDryad Digital Repository, doi:10.5061/dryad.1ns1rn8r7.
Article and author information
Author details
Funding
La Caixa Banking Foundation (LCF/PR/HR17/52150005)
- Leopoldo Petreanu
Fundação para a Ciência e a Tecnologia (LISBOA-01-0145-FEDER 030328)
- Leopoldo Petreanu
Fundação para a Ciência e a Tecnologia (Congento LISBOA-01-0145-FEDER-022170)
- Hedi Young
- Beatriz Belbut
- Margarida Baeta
- Leopoldo Petreanu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Solange P Brown, Johns Hopkins University, United States
Ethics
Animal experimentation: All procedures were reviewed and performed in accordance with the Champalimaud Centre for the Unknown Ethics Committee and approved by the Portuguese Veterinary General Direction.(Ref.No.0421/000/000/2019)
Version history
- Received: June 1, 2020
- Accepted: January 29, 2021
- Accepted Manuscript published: February 1, 2021 (version 1)
- Version of Record published: February 11, 2021 (version 2)
Copyright
© 2021, Young 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.
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Laminar-specific cortico-cortical loops in mouse visual cortex
eLife 10:e59551.
https://doi.org/10.7554/eLife.59551
Further reading
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- Neuroscience
The presence of global synchronization of vasomotion induced by oscillating visual stimuli was identified in the mouse brain. Endogenous autofluorescence was used and the vessel ‘shadow’ was quantified to evaluate the magnitude of the frequency-locked vasomotion. This method allows vasomotion to be easily quantified in non-transgenic wild-type mice using either the wide-field macro-zoom microscopy or the deep-brain fiber photometry methods. Vertical stripes horizontally oscillating at a low temporal frequency (0.25 Hz) were presented to the awake mouse, and oscillatory vasomotion locked to the temporal frequency of the visual stimulation was induced not only in the primary visual cortex but across a wide surface area of the cortex and the cerebellum. The visually induced vasomotion adapted to a wide range of stimulation parameters. Repeated trials of the visual stimulus presentations resulted in the plastic entrainment of vasomotion. Horizontally oscillating visual stimulus is known to induce horizontal optokinetic response (HOKR). The amplitude of the eye movement is known to increase with repeated training sessions, and the flocculus region of the cerebellum is known to be essential for this learning to occur. Here, we show a strong correlation between the average HOKR performance gain and the vasomotion entrainment magnitude in the cerebellar flocculus. Therefore, the plasticity of vasomotion and neuronal circuits appeared to occur in parallel. Efficient energy delivery by the entrained vasomotion may contribute to meeting the energy demand for increased coordinated neuronal activity and the subsequent neuronal circuit reorganization.
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- Medicine
- Neuroscience
Background:
Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine’s molecular mechanisms connect to its neural and behavioral effects.
Methods:
We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets.
Results:
We found that: (i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; (ii) ketamine’s data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level.
Conclusions:
These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry.
Funding:
This study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1–190420) (FXV, KHP); Swiss Neuromatrix Foundation (Grant No. 2016–0111) (FXV, KHP); Swiss National Science Foundation under the framework of Neuron Cofund (Grant No. 01EW1908) (KHP); Usona Institute (2015 – 2056) (FXV).
Clinical trial number:
