A Closer Look at Corticothalamic “Loops”

Rockland, Kathleen S.

doi:10.3389/fncir.2021.632668

Cited by 6 publications

(6 citation statements)

References 50 publications

(60 reference statements)

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“…The results at both of these longer survival times appeared very similar to those at the shorter ones. Consistent with extensive prior literature on corticothalamic neurons 30 , 31 , 32 and with our previous results with corticothalamic injections of ΔG and ΔGL viruses, 1 , 5 the cells labeled in the cortex by both viruses at all time points were pyramidal neurons in layer 6, with a few in layer 5. Furthermore, labeled neurons all appeared morphologically normal even months after injection, with the fine processes of axons and dendrites, including individual spines (rightmost images in Figures 2 B and 2C) clearly visible and without blebbing or other obvious abnormalities.…”

Section: Resultssupporting

confidence: 93%

Third-generation rabies viral vectors allow nontoxic retrograde targeting of projection neurons with greatly increased efficiency

Jin,

Sullivan,

Zhu

et al. 2023

Cell Reports Methods

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Section: Resultssupporting

confidence: 93%

Third-generation rabies viral vectors allow nontoxic retrograde targeting of projection neurons with greatly increased efficiency

Jin,

Sullivan,

Zhu

et al. 2023

Cell Reports Methods

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“…The results at both of these longer survival times appeared very similar to those at the shorter ones. Consistent with extensive prior literature on corticothalamic neurons (Alitto and Usrey, 2003; Rockland, 2021; Rouiller and Welker, 2000) and with our previous results with corticothalamic injections of ΔG and ΔGL viruses (Chatterjee et al, 2018; Wickersham et al, 2007a), the cells labeled in cortex by both viruses at all timepoints were pyramidal neurons in layer 6, with a few in layer 5. Furthermore, labeled neurons all appeared morphologically normal even months after injection, with the fine processes of axons and dendrites, including individual spines (rightmost images in 2F-G) clearly visible and without blebbing or other obvious abnormalities.…”

Section: Resultssupporting

confidence: 92%

Single-deletion-mutant, third-generation rabies viral vectors allow nontoxic retrograde targeting of projection neurons with greatly increased efficiency

Jin

Sullivan

Zhu

et al. 2022

Preprint

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Rabies viral vectors have become important components of the systems neuroscience toolkit, allowing both direct retrograde targeting of projection neurons and monosynaptic tracing of inputs to defined postsynaptic populations, but the rapid cytotoxicity of first-generation (∆G) vectors limits their use to short-term experiments. We recently introduced second-generation, double-deletion-mutant (∆GL) rabies viral vectors, showing that they efficiently retrogradely infect projection neurons and express recombinases effectively but with little to no detectable toxicity; more recently, we have shown that ∆GL viruses can be used for monosynaptic tracing with far lower cytotoxicity than the first-generation system. Here we introduce third-generation (∆L) rabies viral vectors, which, like first-generation vectors, have only a single gene deleted from their genomes (in this case the viral polymerase gene L) but which we find are as nontoxic as second-generation ones: using longitudinal structural and functional two-photon imaging in mouse visual cortex in vivo, we found that they did not kill labeled neurons or perturb their response properties over the entire months-long courses of imaging. Although third-generation vectors are therefore phenotypically very similar to second-generation ones, we show that they have the major advantage of growing to much higher titers, and this key difference results in 25% - 525% increased numbers of retrogradely labeled neurons in vivo. These ∆L rabies viral vectors therefore constitute a new state of the art for nontoxic, pathway-specific expression of recombinases and transactivators in mammalian neurons selected on the basis of their axonal projections. Because replication of deletion-mutant rabies viruses within complementing cells is precisely the process that underlies monosynaptic tracing, the higher replication efficiency of this new class of rabies viral vectors furthermore suggests the potential to provide the foundation of an improved nontoxic monosynaptic tracing system.

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“…Topography is a key organizing factor of neuronal response properties both in cortex and thalamus. Anatomical results show that there is a general correspondence between the topographical organization of sensory representations in the cortex and in the thalamus ( Deschênes et al, 1998 ; Rockland, 2021 ; Shepherd and Yamawaki, 2021 ). However, it is not completely clear whether the pathways looping between the thalamus and cortex are closed (reciprocal) or open (non-reciprocal) at the single cell level, and with respect to the response properties of the pre-and post-synaptic cells (alignment, misalignment).…”

Section: Discussionmentioning

confidence: 99%

“…Top-down L6 CT excitatory projections target distal regions of TC cell dendrites, while also branching to provide disynaptic GABAergic input to TC cells via TRN and local interneurons ( Deschênes et al, 1998 ; Kimura et al, 2007 ; Landisman and Connors, 2007 ; Mease et al, 2014 ; Crandall et al, 2015 ). The L6 excitatory (direct) and inhibitory (indirect) projections are arranged both in closed-and open-loop systems ( Land et al, 1995 ; Deschênes et al, 1998 ; Lam and Sherman, 2010 ; Brown et al, 2020 ; Rockland, 2021 ; Shepherd and Yamawaki, 2021 ). Although the anatomical organization of the two branches of the CT projection at the single cell level is still unclear, the L6 excitatory and inhibitory footprints to individual TC cells can originate from areas located tens of micrometers apart or more in L6 ( Lam and Sherman, 2010 ).…”

Section: Functional Organization Of Thalamocortical Circuitsmentioning

confidence: 99%

A mechanism for deviance detection and contextual routing in the thalamus: a review and theoretical proposal

Varela,

Moreira,

Kocaoglu

et al. 2024

Front. Neurosci.

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Predictive processing theories conceptualize neocortical feedback as conveying expectations and contextual attention signals derived from internal cortical models, playing an essential role in the perception and interpretation of sensory information. However, few predictive processing frameworks outline concrete mechanistic roles for the corticothalamic (CT) feedback from layer 6 (L6), despite the fact that the number of CT axons is an order of magnitude greater than that of feedforward thalamocortical (TC) axons. Here we review the functional architecture of CT circuits and propose a mechanism through which L6 could regulate thalamic firing modes (burst, tonic) to detect unexpected inputs. Using simulations in a model of a TC cell, we show how the CT feedback could support prediction-based input discrimination in TC cells by promoting burst firing. This type of CT control can enable the thalamic circuit to implement spatial and context selective attention mechanisms. The proposed mechanism generates specific experimentally testable hypotheses. We suggest that the L6 CT feedback allows the thalamus to detect deviance from predictions of internal cortical models, thereby supporting contextual attention and routing operations, a far more powerful role than traditionally assumed.

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A Closer Look at Corticothalamic “Loops”

Cited by 6 publications

References 50 publications

Third-generation rabies viral vectors allow nontoxic retrograde targeting of projection neurons with greatly increased efficiency

Third-generation rabies viral vectors allow nontoxic retrograde targeting of projection neurons with greatly increased efficiency

Single-deletion-mutant, third-generation rabies viral vectors allow nontoxic retrograde targeting of projection neurons with greatly increased efficiency

A mechanism for deviance detection and contextual routing in the thalamus: a review and theoretical proposal

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