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.
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•Ventral tegmental area (VTA)-glutamate neurons encode innate defensive behavior•A single VTA-glutamate neuron receives multiple hypothalamic excitatory inputs•Hypothalamic excitatory inputs to VTA-glutamate neurons convey treating information
Innate defensive behaviors are unlearned responses, evolutionarily selected to increase chances of survival. Here, Barbano et al. report that ventral tegmental area glutamatergic neurons are activated by and required for innate defensive responses and that information on threatening stimuli to these glutamate neurons is relayed by hypothalamic excitatory neurons.