Temporal prediction error triggers amygdala-dependent memory updating in appetitive operant conditioning in rats

Abstract

Reinforcement learning theories postulate that prediction error, i.e., a discrepancy between the actual and expected outcomes, drives reconsolidation and new learning, inducing an updating of the initial memory. Pavlovian studies have shown that prediction error detection is a fundamental mechanism in triggering amygdala-dependent memory updating, where the temporal relationship between stimuli plays a critical role. However, in contrast to the well-established findings in aversive situations (e.g., fear conditioning), only few studies exist on prediction error in appetitive operant conditioning, and even less with regard to the role of temporal parameters. To explore if temporal prediction error in an appetitive operant paradigm could generate an updating and consequent reconsolidation and/or new learning of temporal association, we ran four experiments in adult male rats. Experiment 1 verified whether an unexpected delay in the time of reward’s availability (i.e., a negative temporal prediction error) in a single session produces an updating in long-term memory of temporal expectancy in an appetitive operant conditioning. Experiment 2 showed that negative prediction errors, either due to the temporal change or through reward omission, increased in the basolateral amygdala nucleus (BLA) the activation of a protein that is critical for memory formation. Experiment 3 revealed that the presence of a protein synthesis inhibitor (anisomycin) in the BLA during the session when the reward was delayed (Error session) affected the temporal updating. Finally, Experiment 4 showed that anisomycin, when infused immediately after the Error session, interfered with the long-term memory of the temporal updating. Together, our study demonstrated an involvement of BLA after a change in temporal and reward contingencies, and in the resulting updating in long-term memory in appetitive operant conditioning.

Neural networks representing temporal expectation in mice

“…3B,C) (Sun et al, 2021;Todd et al, 2019). Interestingly, the amygdala (AMY) showed a significant positive BOLD contrast during audio-visual stimulation which might support their role in triggering temporal prediction errors (Tavares et al, 2022). Altogether, differences in BOLD activity patterns both before and after training occur across diverse brain networks between mice adopting a target-attending or a target-invariant behavioural strategy during the task, but are particularly prominent in areas involved in processing task-relevant information across learning and differ more significantly after training in the presence of the visually-evoked target stimulus.…”

“…3B,C) (Sun et al, 2021; Todd et al, 2019). Interestingly, the amygdala (AMY) showed a significant positive BOLD contrast during audio-visual stimulation which might support their role in triggering temporal prediction errors (Tavares et al, 2022).…”

Temporal recalibration in response to delayed visual feedback of active versus passive actions: an fMRI study

“…The activation cluster in the hippocampus also extends into the amygdala. In previous animal research, it has been shown that temporal prediction errors can trigger memory updating processes in the amygdala in appetitive and aversive association learning contexts 41 , 42 , suggesting a role of the amygdala in predictive processes. In the human context, studies suggest the amygdala to be involved in the processing of body ownership 43 , 44 .…”