Single-cell–initiated monosynaptic tracing reveals layer-specific cortical network modules

Wertz, Adrian; Trenholm, Stuart; Yonehara, Keisuke; Hillier, Dániel; Raics, Z.; Leinweber, Marcus; Szalay, Gergely; Ghanem, Alexander; Keller, Georg B.; Rózsa, Balázs; Conzelmann, Karl‐Klaus; Roska, Botond

doi:10.1126/science.aab1687

Cited by 225 publications

(210 citation statements)

References 35 publications

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“…Although it is conceivable that the transsynaptic efficiency of SAD-B19 could be improved with modifications to the complementation vectors (eg. DeNardo et al, 2015) or the use of alternate complementation methods (Rancz et al, 2011; Wertz et al, 2015) it is highly likely that the spread of CVS-N2c could be improved in the same way. Thus the use of the CVS-N2c ΔG viral strain for anatomical studies has the potential to uncover aspects of neuronal connectivity inaccessible through the use of SAD-B19 ΔG .…”

Section: Discussionmentioning

confidence: 99%

Rabies Virus CVS-N2c ΔG Strain Enhances Retrograde Synaptic Transfer and Neuronal Viability

Reardon

Murray

Túri

et al. 2016

Neuron

275

321

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Summary Virally-based transsynaptic tracing technologies are powerful experimental tools for neuronal circuit mapping. The glycoprotein-deletion variant of the SAD-B19 vaccine strain rabies virus (RABV) has been the reagent of choice in monosynaptic tracing, since it permits the mapping of synaptic inputs to genetically marked neurons. Since its introduction, new helper viruses and reagents that facilitate complementation have enhanced the efficiency of SAD-B19ΔG transsynaptic transfer, but there has been little focus on improvements to the core RABV strain. Here we generate a new deletion-mutant strain, CVS-N2cΔG, and examine its neuronal toxicity and efficiency in directing retrograde transsynaptic transfer. We find that by comparison with SAD-B19ΔG, the CVS-N2cΔG strain exhibits a reduction in neuronal toxicity and a marked enhancement in transsynaptic neuronal transfer. We conclude that the CVS-N2cΔG strain provides a more effective means of mapping neuronal circuitry and of monitoring and manipulating neuronal activity in vivo in the mammalian central nervous system.

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Section: Discussionmentioning

confidence: 99%

Rabies Virus CVS-N2c ΔG Strain Enhances Retrograde Synaptic Transfer and Neuronal Viability

Reardon

Murray

Túri

et al. 2016

Neuron

275

321

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“…Therefore, experimental evidence strongly suggests that, as in L2/3 (refs. [36][37][38], excitatory neurons in L4 with similar tuning might also preferentially connect with each other. This connectivity pattern, in which locally interconnected neurons sample shared long-range inputs, also supports models of amplification without changes in tuning properties of TC responses by recurrent excitation [13][14][15] .…”

Section: Shared Tc Innervation Of Connected L4 Neuronsmentioning

confidence: 96%

Multilaminar networks of cortical neurons integrate common inputs from sensory thalamus

2016

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Neurons in the thalamorecipient layers of sensory cortices integrate thalamic and recurrent cortical input. Cortical neurons form fine-scale, functionally cotuned networks, but whether interconnected cortical neurons within a column process common thalamocortical inputs is unknown. We tested how local and thalamocortical connectivity relate to each other by analyzing cofluctuations of evoked responses in cortical neurons after photostimulation of thalamocortical axons. We found that connected pairs of pyramidal neurons in layer (L) 4 of mouse visual cortex share more inputs from the dorsal lateral geniculate nucleus than nonconnected pairs. Vertically aligned connected pairs of L4 and L2/3 neurons were also preferentially contacted by the same thalamocortical axons. Our results provide a circuit mechanism for the observed amplification of sensory responses by L4 circuits. They also show that sensory information is concurrently processed in L4 and L2/3 by columnar networks of interconnected neurons contacted by the same thalamocortical axons.

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“…Of particular interest is the extent of remodeling of the input network to pMO: in fact, the type and amount of projection to pMO determines not only the output from MO, which is strongly related to the execution of movements; in addition, the synaptic inputs are strong regulators of neuronal activity pattern and may influence activity-dependent pathogenic factors (Roselli and Caroni, 2015; Bading, 2017). To date, connectivity maps have been obtained at mesoscale (Oh et al, 2014; Mitra, 2014) or at cellular resolution (Mao et al, 2011; Wertz et al, 2015) only for wild-type models.…”

Section: Introductionmentioning

confidence: 99%

Stage-dependent remodeling of projections to motor cortex in ALS mouse model revealed by a new variant retrograde-AAV9

Commisso

Ding

Varadi

et al. 2018

eLife

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Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motoneurons in the primary motor cortex (pMO) and in spinal cord. However, the pathogenic process involves multiple subnetworks in the brain and functional MRI studies demonstrate an increase in functional connectivity in areas connected to pMO despite the ongoing neurodegeneration. The extent and the structural basis of the motor subnetwork remodeling in experimentally tractable models remain unclear. We have developed a new retrograde AAV9 to quantitatively map the projections to pMO in the SOD1(G93A) ALS mouse model. We show an increase in the number of neurons projecting from somatosensory cortex to pMO at presymptomatic stages, followed by an increase in projections from thalamus, auditory cortex and contralateral MO (inputs from 20 other structures remains unchanged) as disease advances. The stage- and structure-dependent remodeling of projection to pMO in ALS may provide insights into the hyperconnectivity observed in ALS patients.

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Single-cell–initiated monosynaptic tracing reveals layer-specific cortical network modules

Cited by 225 publications

References 35 publications

Rabies Virus CVS-N2c ΔG Strain Enhances Retrograde Synaptic Transfer and Neuronal Viability

Rabies Virus CVS-N2c ΔG Strain Enhances Retrograde Synaptic Transfer and Neuronal Viability

Multilaminar networks of cortical neurons integrate common inputs from sensory thalamus

Stage-dependent remodeling of projections to motor cortex in ALS mouse model revealed by a new variant retrograde-AAV9

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