Fear learning is a fundamental behavioral process shared by rodents and humans and requires dopamine (DA) release. Experience-dependent synaptic plasticity, a cellular form of learning and memory, occurs on DA neurons while an organism is engaged in aversive experiences. However, whether synaptic plasticity on DA neurons is causally involved in aversion learning is unknown. Here, we took advantage of the ability of the ATPase Thorase in regulating the internalization of AMPA receptors (AMPARs) in order to artificially manipulate glutamatergic synaptic plasticity in DA neurons. Genetic ablation of Thorase in DAT+ neurons produced increased AMPAR surface expression and impaired the induction of both long-term depression (LTD) and long-term potentiation (LTP). Strikingly, animals lacking Thorase in DAT+ neurons expressed greater associative learning in a fear-conditioning paradigm without showing fear generalization or anxiety. In conclusion, our data provides a novel, causal link between induction of synaptic plasticity onto DA neurons and fear learning. In the current project we characterize the molecular and physiological role of Thorase protein in respect to the internalization of AMPAR and in the occurrence of an activity-dependent glutamatergic synaptic plasticity in the context of DA neurons. Additionally we show that animals lacking Thorase from DA neurons display an increase propensity toward learning and memory aversive experiences.
| Tejeda, Hugo A; Wu, Jocelyn; Kornspun, Alana R et al. (2017) Pathway- and Cell-Specific Kappa-Opioid Receptor Modulation of Excitation-Inhibition Balance Differentially Gates D1 and D2 Accumbens Neuron Activity. Neuron 93:147-163 |
