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VTA Glutamatergic Neurons Mediate Innate Defensive Behaviors

Defensive escape behavior is mediated by ventral tegmental area (VTA) glutamatergic neurons that receive excitatory inputs from lateral hypothalamic area (LHA) glutamate fibers. Lateral hypothalamic area glutamate neurons convey information on innate threats by establish excitatory synapses more frequently on ventral tegmental are glutamate neurons than on dopamine neurons. Activation of ventral tegmental area glutamate neurons by lateral hypothalamic area glutamate fibers encode innate escape behavior.

A figure from this study – click for detailed description.

Hot Off the Press – November 11 , 2020

The role of ventral tegmental area (VTA) in motivated behavior is well established. However, Barbano et al., demonstrated that a subset of VTA neurons, that utilizes glutamate as signaling molecule, mediates innate defensive behaviors, evolutionary selected responses that promote escaping from dangerous situations. Alterations in innate defensive behavior have been associated with psychiatric disorders, such as PTSD and autism. The unanticipated role of VTA glutamate neurons in mediating innate defense opens new avenues to determine their role in brain disorders associated with the dysregulation of innate defensive behaviors in general, and dysregulation associated with intake of drugs of abuse in particular.

Publication Information

Barbano, Flavia M; Wang, Hui-Ling; Zhang, Shiliang; Miranda-Barrientos, Jorge; Estrin, David J; Figueroa-González, Almaris; Liu, Bing; Barker, David J; Morales, Marisela

VTA Glutamatergic Neurons Mediate Innate Defensive Behaviors Journal Article

In: Neuron, vol. 107, no. 2, pp. 368–382.e8, 2020, ISBN: 0896-6273.

Abstract | Links

@article{Barbano:2020aa,
title = {VTA Glutamatergic Neurons Mediate Innate Defensive Behaviors},
author = {Flavia M Barbano and Hui-Ling Wang and Shiliang Zhang and Jorge Miranda-Barrientos and David J Estrin and Almaris Figueroa-González and Bing Liu and David J Barker and Marisela Morales},
url = {https://pubmed.ncbi.nlm.nih.gov/32442399/},
doi = {10.1016/j.neuron.2020.04.024},
isbn = {0896-6273},
year = {2020},
date = {2020-07-22},
urldate = {2020-07-22},
booktitle = {Neuron},
journal = {Neuron},
volume = {107},
number = {2},
pages = {368--382.e8},
publisher = {Elsevier},
abstract = {The ventral tegmental area (VTA) has dopamine, GABA, and glutamate neurons, which have been implicated in reward and aversion. Here, we determined whether VTA-glutamate or -GABA neurons play a role in innate defensive behavior. By VTA cell-type-specific genetic ablation, we found that ablation of glutamate, but not GABA, neurons abolishes escape behavior in response to threatening stimuli. We found that escape behavior is also decreased by chemogenetic inhibition of VTA-glutamate neurons and detected increases in activity in VTA-glutamate neurons in response to the threatening stimuli. By ultrastructural and electrophysiological analysis, we established that VTA-glutamate neurons receive a major monosynaptic glutamatergic input from the lateral hypothalamic area (LHA) and found that photoinhibition of this input decreases escape responses to threatening stimuli. These findings indicate that VTA-glutamate neurons are activated by and required for innate defensive responses and that information on threatening stimuli to VTA-glutamate neurons is relayed by LHA-glutamate neurons.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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The ventral tegmental area (VTA) has dopamine, GABA, and glutamate neurons, which have been implicated in reward and aversion. Here, we determined whether VTA-glutamate or -GABA neurons play a role in innate defensive behavior. By VTA cell-type-specific genetic ablation, we found that ablation of glutamate, but not GABA, neurons abolishes escape behavior in response to threatening stimuli. We found that escape behavior is also decreased by chemogenetic inhibition of VTA-glutamate neurons and detected increases in activity in VTA-glutamate neurons in response to the threatening stimuli. By ultrastructural and electrophysiological analysis, we established that VTA-glutamate neurons receive a major monosynaptic glutamatergic input from the lateral hypothalamic area (LHA) and found that photoinhibition of this input decreases escape responses to threatening stimuli. These findings indicate that VTA-glutamate neurons are activated by and required for innate defensive responses and that information on threatening stimuli to VTA-glutamate neurons is relayed by LHA-glutamate neurons.

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  • https://pubmed.ncbi.nlm.nih.gov/32442399/
  • doi:10.1016/j.neuron.2020.04.024

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