Activity in the prelimbic prefrontal cortex encodes individual differences in approach-avoidance conflict in rats

AQUINO-MIRANDA, G.; FERNANDEZ LEON, J.A.; ENGELKE, D.S.; GODSON, A.; DO-MONTE, F.H.

houston

Conferencia; 2021 SfN Neuroscience; 2021

Neurons in the prelimbic subregion of the prefrontal cortex (PL) respond to both reward- and threat-associated cues. However, whether PL activity regulates the animals’ decision to approach or avoid such cues as remains unknown. To address this question, male Long-Evans rats with single-unit recording electrodes implanted in PL were initially trained to press a bar for sucrose during the presentation of audiovisual cues. Next, rats were fear conditioned by pairing a neutral odor with electrical footshocks. During the test session, rats were placed in an arena and exposed to three phases: only audiovisual cues (reward), only odor cues (fear), or both simultaneously (conflict). During the reward phase, animals pressed the bar immediately after the onset of the food cues. In the fear phase, animals showed robust defensive behaviors characterized by high levels of freezing, avoidance, and risk-assessment responses. Interestingly, two different behavioral phenotypes emerged during the conflict phase: rats that continued searching for food (pressers) vs. rats that remained in the hidden area and showed suppression of food-seeking responses (non-pressers). PL recordings during the reward phase revealed a greater number of reward-cue responses in pressers (~33% of 237 neurons), when compared to non-pressers (~21% of 89 neurons; Fisher Exact Test, p = 0.042). Notably, the magnitude of reward-cue responses observed during the conflict phase was similar to the reward phase for pressers, but was drastically reduced for non-pressers. Using a combination of recordings and optogenetics for photoidentification of distinct subtypes of PL neurons in pressers, we found that ~31% of PL glutamatergic (PLGLUT) neurons inhibited their spontaneous firing rate during the reward phase, when compared to baseline. Presentation of the conditioned odor during the fear phase disinhibited ~67% of these PLGLUT neurons, whereas the introduction of reward cues during the conflict phase restored the inhibition to the same levels as the reward phase. In contrast, changes in spontaneous firing rate of PL GABAergic neurons were similar across the different phases. Moreover, photoactivation of PLGLUT neurons during the onset of the reward cues reduced reward-seeking responses in pressers, whereas photoinhibition of PLGLUT neurons in non-pressers reduced defensive responses and biased animals’ behavior toward the food area during conflict (Wilcoxon test, all p values < 0.05). Together, our results establish a role for PL in the regulation of approach-avoidance conflict by demonstrating that reduced activity in PLGLUT neurons is associated with increased risky sucrose-seeking behavior.