Transneuronal Circuit Analysis with Pseudorabies Viruses

Card, J. Patrick; Enquist, Lynn W.

doi:10.1002/0471142301.ns0105s68

Cited by 84 publications

(77 citation statements)

References 111 publications

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“…After three freeze-thaw cycles, cell debris was removed by centrifugation twice at 1000 × g for 5 minutes and the supernatant was then used for experiments. The titer of viral stocks was determined using standard plaque assays on PK15 cells 19 , with titers expressed in plaque-forming units (PFU).…”

Section: Methodsmentioning

confidence: 99%

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A specific area of olfactory cortex involved in stress hormone responses to predator odours

Kondoh

et al. 2016

Nature

137

143

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Instinctive reactions to danger are critical to the perpetuation of species and are observed throughout the animal kingdom. The scent of predators induces an instinctive fear response in mice that includes behavioral changes as well as a surge in blood stress hormones that mobilizes multiple body systems to escape impending danger1,2. How the olfactory system routes predator signals detected in the nose to achieve these effects is unknown. Here we identify a specific area of the olfactory cortex that induces stress hormone responses to volatile predator odors. Using monosynaptic and polysynaptic viral tracers, we found that multiple olfactory cortical areas transmit signals to hypothalamic CRH (corticotropin releasing hormone) neurons, which control stress hormone levels. However, only one minor cortical area, the amygdalo-piriform transition area (AmPir), contained neurons upstream of CRH neurons that were activated by volatile predator odors. Chemogenetic stimulation of AmPir activated CRH neurons and induced an increase in blood stress hormone, mimicking an instinctive fear response. Moreover, chemogenetic silencing of AmPir markedly reduced the stress hormone response to predator odors without affecting a fear behavior. These findings suggest that AmPir, a small area comprising <5% of the olfactory cortex, plays a key role in the hormonal component of the instinctive fear response to volatile predator scents.

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Section: Methodsmentioning

confidence: 99%

“…We developed two Cre recombinase-dependent Bartha pseudorabies viruses (PRVs) that have nonfunctional thymidine kinase (TK) genes, but require TK to replicate and travel retrogradely across synapses 19,20 , and a lentivirus (LVF2TK) with Cre-dependent expression of hemagglutinin-tagged TK (HA-TK) (Fig. 1a).…”

mentioning

confidence: 99%

A specific area of olfactory cortex involved in stress hormone responses to predator odours

Kondoh

et al. 2016

Nature

137

143

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“…Currently, transsynaptic neurotropic viruses are very valuable tools for identification of synaptic connections and neural networks. Among the neurotropic viruses, pseudorabies viruses (PRVs) are often used for circuit analysis and revealing organization of the nervous system (107–110). PRVs, such as PRV-152, an attenuated viral strain driving the expression of EGFP, are reliable and effective transsynaptic tracers, and numerous publications reported consistent organ-specific labeling of neurons (111–115).…”

Section: Liver-related Neurons In the Hypothalamusmentioning

confidence: 99%

Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism

2017

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Metabolic disorders, particularly aberrations in lipid homeostasis, such as obesity, type 2 diabetes mellitus, and hypertriglyceridemia often manifest together as the metabolic syndrome (MetS). Despite major advances in our understanding of the pathogenesis of these disorders, the prevalence of the MetS continues to rise. It is becoming increasingly apparent that intermediary metabolism within the central nervous system is a major contributor to the regulation of systemic metabolism. In particular, lipid metabolism within the brain is tightly regulated to maintain neuronal structure and function and may signal nutrient status to modulate metabolism in key peripheral tissues such as the liver. There is now a growing body of evidence to suggest that fatty acid (FA) sensing in hypothalamic neurons via accumulation of FAs or FA metabolites may signal nutritional sufficiency and may decrease hepatic glucose production, lipogenesis, and VLDL-TG secretion. In addition, recent studies have highlighted the existence of liver-related neurons that have the potential to direct such signals through parasympathetic and sympathetic nervous system activity. However, to date whether these liver-related neurons are FA sensitive remain to be determined. The findings discussed in this review underscore the importance of the autonomic nervous system in the regulation of systemic metabolism and highlight the need for further research to determine the key features of FA neurons, which may serve as novel therapeutic targets for the treatment of metabolic disorders.

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“…However, classical tracers such as horseradish peroxidase or fluorogold do not readily discriminate based on cell type. Several rabies or herpes based viral vectors have been developed that target genetically defined cell types and spread transsynaptically to label afferent inputs (Callaway, 2008; Card and Enquist, 2014; Osakada et al, 2011; Wall et al, 2010; Wickersham et al, 2007). Combined use of modified rabies virus (Rb) together with ‘helper’ Adeno-associated virus (AAV) vectors have proven particularly amenable toward this goal across a variety of structures and neuron types (Wall et al, 2013; Weissbourd et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Afferent Inputs to Neurotransmitter-Defined Cell Types in the Ventral Tegmental Area

Osakada²,

et al. 2016

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The ventral tegmental area (VTA) plays a central role in the neural circuit control of behavioral reinforcement. Though considered a dopaminergic nucleus, the VTA contains substantial heterogeneity in neurotransmitter type, containing also GABA and glutamate neurons. Here we used a combinatorial viral approach to transsynaptically label afferents to defined VTA dopamine, GABA, or glutamate neurons. Surprisingly, we find that these populations received qualitatively similar inputs, with dominant and comparable projections from the lateral hypothalamus, raphe, and ventral pallidum. However, notable differences were observed with striatal regions and globus pallidus providing a greater share of input to VTA dopamine neurons, cortical input preferentially on to glutamate neurons, and GABA neurons receiving proportionally more input from the lateral habenula and laterodorsal tegmental nucleus. By comparing inputs to each of the transmitter-defined VTA cell types this study sheds important light on the systems-level organization of diverse inputs to VTA.

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Transneuronal Circuit Analysis with Pseudorabies Viruses

Cited by 84 publications

References 111 publications

A specific area of olfactory cortex involved in stress hormone responses to predator odours

A specific area of olfactory cortex involved in stress hormone responses to predator odours

Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism

Afferent Inputs to Neurotransmitter-Defined Cell Types in the Ventral Tegmental Area

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