Anterior cingulate neurons signal neutral cue pairings during sensory preconditioning

Abstract

Of all frontocortical subregions, the anterior cingulate cortex (ACC) has perhaps the most overlapping theories of function. [1][2][3] Recording studies in rats, humans, and other primates have reported diverse neural responses that support many theories, [4][5][6][7][8][9][10][11][12] yet nearly all these studies have in common tasks in which one event reliably predicts another. This leaves open the possibility that ACC represents associative pairing of events, independent of their overt biological significance. Sensory preconditioning 13 provides an opportunity to test this. In the first phase, preconditioning, value-neutral sensory stimuli are paired (A/B). To test whether this was learned, subjects are given standard conditioning during which one of the previously neutral sensory cues is paired with a biologically meaningful outcome (B/outcome). During the final probe test, the neutral cue which was never paired with a biologically meaningful outcome is presented alone (A/) and will elicit a conditional response, suggesting that subjects had learned the associative structure during preconditioning and use that knowledge to infer presentation of the biologically relevant outcome (A/B/outcome). Inference-based responding demonstrates a fundamental property of model-based reasoning 14,15 and requires learning of the associations between neutral stimuli before rewards are introduced. 16-19 ACC neurons developed firing patterns that reflected the learning of sensory associations during preconditioning, even though no rewards were present. The strength of these correlates predicted rats' ability to later mobilize and use that associative information during the probe test. These results demonstrate that clear biological significance is not necessary to produce correlates of learning in ACC. RESULTS Rats learn sensory associations, which are mobilized during the probe testTo test whether anterior cingulate cortex (ACC) neurons represent the pairing between biologically neutral events, we recorded single-unit activity during training in a sensory preconditioning task like that used in previous studies (Figure 1A). 20,21 Rats were implanted with microelectrodes in ACC (Figure 1E) and given one session of food-port shaping, after which training began. During two days of preconditioning rats were exposed to two separate, value-neutral sensory cue pairs (A/B; C/D). Responding to each cue was negligible and similar (Figure 1B). Subsequently, to reveal latent learning of the cue-cue pairings, rats were given six sessions of reward conditioning, in which cue B was paired with reward and cue D was presented without reward, followed by a probe test, in which cues A and C were also presented, unrewarded. As expected, rats responded more to cue B than to cue D during conditioning (Figure 1C) and more to A than C in the final probe test (Figure 1D, bottom), consistent with successful preconditioning.ACC neurons fire to sensory cues and form associative correlates Consistent with other findings where ACC neurons fired to sensory c...

Prefrontal encoding of an internal model for emotional inference

“…Moreover, the flexibility of this representation in conditions such as extinction allows for the maintenance of the relevant sensory associative information, but excision of the connection between the sensory stimulus which has been devalued and the representation of the aversive experience it was associated with. Several potential regions which are anatomically connected with the dmPFC have been implicated in processing sensory-sensory or contextual models mediating appetitive and aversive learning including perirhinal, anterior cingulate and orbitofrontal cortices as well as the hippocampus 17,18,21,46,[58][59][60][61] . Further studies are required to determine how these regions interact to build sensory and value-based internal models and how more complex models involving multiple aversive and reward-based associations are encoded in dmPFC.…”

“…Several studies examining aversive and reward related behaviors have identified brain regions which participate in encoding models of the associative relationships between sensory stimuli, independent of whether they were associated with salient events (i.e. a sensory model) [17][18][19][20][21] . However, whether and, if so, how the brain encodes models of emotionally relevant associations and whether emotional models are distinct from internal sensory models has not been examined 22 .…”