A half century of experimental neuroanatomical tracing

Lanciego, José L.; Wouterlood, Floris G.

doi:10.1016/j.jchemneu.2011.07.001

Cited by 192 publications

(167 citation statements)

References 209 publications

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“…monkey | anatomy | neocortex T he development of retrograde tract tracing methods has made possible high-resolution connectivity analysis in the central nervous system at the single-cell level (1). Considerable progress has been made in describing the functional regionalization of the cortex and the pathways linking cortical areas (2,3).…”

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confidence: 99%

The role of long-range connections on the specificity of the macaque interareal cortical network

Markov

Ercsey-Ravasz

Lamy

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

201

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We investigated the influence of interareal distance on connectivity patterns in a database obtained from the injection of retrograde tracers in 29 areas distributed over six regions (occipital, temporal, parietal, frontal, prefrontal, and limbic). One-third of the 1,615 pathways projecting to the 29 target areas were reported only recently and deemed new-found projections (NFPs). NFPs are predominantly long-range, low-weight connections. A minimum dominating set analysis (a graph theoretic measure) shows that NFPs play a major role in globalizing input to small groups of areas. Randomization tests show that ( i ) NFPs make important contributions to the specificity of the connectivity profile of individual cortical areas, and ( ii ) NFPs share key properties with known connections at the same distance. We developed a similarity index, which shows that intraregion similarity is high, whereas the interregion similarity declines with distance. For area pairs, there is a steep decline with distance in the similarity and probability of being connected. Nevertheless, the present findings reveal an unexpected binary specificity despite the high density (66%) of the cortical graph. This specificity is made possible because connections are largely concentrated over short distances. These findings emphasize the importance of long-distance connections in the connectivity profile of an area. We demonstrate that long-distance connections are particularly prevalent for prefrontal areas, where they may play a prominent role in large-scale communication and information integration.

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mentioning

confidence: 99%

The role of long-range connections on the specificity of the macaque interareal cortical network

Markov

Ercsey-Ravasz

Lamy

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

201

218

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“…Earlier attempts were based on direct injections of compounds that mostly rely on axonal transport. Depending on the direction of the transport, anterograde and retrograde tracers can be discerned, such as the plant enzyme horse radish peroxidase, Fluoro-Gold and the non-toxic C fragment of the tetanus toxin (TTC) (Lanciego and Wouterlood 2011) used as retrograde tracers, and biotinylated dextran amine and its variants, the plant lectins Phaseolus vulgaris-leucoagglutinin (PHA-L) and wheat germ agglutinin (WGA) as anterograde tracers (Lanciego and Wouterlood 2011). Yet, these tracers are not perfectly unidirectional but rather are transported in both directions with a preference for one direction (Lanciego and Wouterlood 2011).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of WGA–Cre-dependent topological transgene expression in the rodent brain

et al. 2016

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Novel neuromodulation techniques in the field of brain research, such as optogenetics, prompt to target specific cell populations. However, not every subpopulation can be distinguished based on brain area or activity of specific promoters, but rather on topology and connectivity. A fascinating tool to detect neuronal circuitry is based on the transsynaptic tracer, wheat germ agglutinin (WGA). When expressed in neurons, it is transported throughout the neuron, secreted, and taken up by synaptically connected neurons. Expression of a WGA and Cre recombinase fusion protein using a viral vector technology in Cre-dependent transgenic animals allows to trace neuronal network connections and to induce topological transgene expression. In this study, we applied and evaluated this technology in specific areas throughout the whole rodent brain, including the hippocampus, striatum, substantia nigra, and the motor cortex. Adeno-associated viral vectors (rAAV) encoding the WGA-Cre fusion protein under control of a CMV promoter were stereotactically injected in Rosa26-STOP-EYFP transgenic mice. After 6 weeks, both the number of transneuronally labeled YFP ? / mCherry -cells and the transduced YFP ? /mCherry ? cells were quantified in the connected regions. We were able to trace several connections using WGA-Cre transneuronal labeling; however, the labeling efficacy was region-dependent. The observed transneuronal labeling mostly occurred in the anterograde direction without the occurrence of multi-synaptic labeling. Furthermore, we were able to visualize a specific subset of newborn neurons derived from the subventricular zone based on their connectivity.

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“…In this approach, when diphtheria toxin was administrated, it was transferred only into the targeted cells and induced cell death [78,182,183]. Cholera toxin B fragment and wheat germ agglutinin are highly sensitive retrograde tracers [184][185][186]. Neurotoxins, including diphtheria toxin, botulinum toxin, ricin, and saporin, have been conjugated with these retrograde tracers to kill connected neurons [187][188][189][190].…”

Section: Cell-specific Neurotoxinsmentioning

confidence: 99%

Selective Manipulation of Neural Circuits

Park

Carmel

2016

Neurotherapeutics

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Unraveling the complex network of neural circuits that form the nervous system demands tools that can manipulate specific circuits. The recent evolution of genetic tools to target neural circuits allows an unprecedented precision in elucidating their function. Here we describe two general approaches for achieving circuit specificity. The first uses the genetic identity of a cell, such as a transcription factor unique to a circuit, to drive expression of a molecule that can manipulate cell function. The second uses the spatial connectivity of a circuit to achieve specificity: one genetic element is introduced at the origin of a circuit and the other at its termination. When the two genetic elements combine within a neuron, they can alter its function. These two general approaches can be combined to allow manipulation of neurons with a specific genetic identity by introducing a regulatory gene into the origin or termination of the circuit. We consider the advantages and disadvantages of both these general approaches with regard to specificity and efficacy of the manipulations. We also review the genetic techniques that allow gain-and loss-of-function within specific neural circuits. These approaches introduce light-sensitive channels (optogenetic) or drug sensitive channels (chemogenetic) into neurons that form specific circuits. We compare these tools with others developed for circuit-specific manipulation and describe the advantages of each. Finally, we discuss how these tools might be applied for identification of the neural circuits that mediate behavior and for repair of neural connections.

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A half century of experimental neuroanatomical tracing

Cited by 192 publications

References 209 publications

The role of long-range connections on the specificity of the macaque interareal cortical network

The role of long-range connections on the specificity of the macaque interareal cortical network

Evaluation of WGA–Cre-dependent topological transgene expression in the rodent brain

Selective Manipulation of Neural Circuits

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