Abstract
Survival depends on the ability of animals to select the appropriate behavior in response to threat and safety sensory cues. However, the synaptic and circuit mechanisms by which the brain learns to encode accurate predictors of threat and safety remain largely unexplored. Here, we show that frontal association cortex (FrA) pyramidal neurons of mice integrate auditory cues and basolateral amygdala (BLA) inputs non-linearly in a NMDAR-dependent manner. We found that the response of FrA pyramidal neurons was more pronounced to Gaussian noise than to pure frequency tones, and that the activation of BLA-to-FrA axons was the strongest in between conditioning pairings. Blocking BLA-to-FrA signaling specifically at the time of presentation of Gaussian noise (but not 8 kHz tone) between conditioning trials impaired the formation of auditory fear memories. Taken together, our data reveal a circuit mechanism that facilitates the formation of fear traces in the FrA, thus providing a new framework for probing discriminative learning and related disorders.
Highlights
Discriminative learning is an important survival strategy that depends on the repeated contingency and contiguity between sensory cues and the events that they must predict (Hall, 2002)
To detect changes in Vm induced by the auditory stimulation, we computed the cumulative depolarization over time, from which was subtracted the linear regression calculated during the baseline period prior to auditory stimulation (Figure 1C,D; Figure 1—figure supplement 2A,B)
The present study investigates the role of the basolateral complex of the amygdala (BLA)-to-frontal association cortex (FrA) circuit in the integration of auditory cues, and how this process participates in the acquisition of fear traces during conditioning
Summary
Discriminative learning is an important survival strategy that depends on the repeated contingency and contiguity between sensory cues (conditioned stimuli, CS) and the events (e.g. danger, safety) that they must predict (unconditioned stimuli, US) (Hall, 2002) It has been classically studied by using differential fear-conditioning paradigms where two different auditory CS are positively (CS+) and negatively (CS-) paired in time with an aversive US (e.g. foot shock). The medial prefrontal cortex (mPFC) has appeared over the past decade as a critical region that shapes behaviors in response to both aversive and non-aversive environmental cues (Likhtik and Paz, 2015; Likhtik et al, 2014; Stujenske et al, 2014) These effects of the mPFC possibly rely on the specific interaction between its different subdivisions (i.e.prelimbic [PL] and infralimbic [IL] cortices) and the basolateral complex of the amygdala (BLA) (Senn et al, 2014; Sierra-Mercado et al, 2011; Vidal-Gonzalez et al, 2006).
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