Neuronal Correlates of Reward vs. Fear Memory Discrimination in the Prelimbic Cortex

FERNANDEZ LEON, JOSE A.; ENGELKE, DOUGLAS; NAIM-RASHEED, MARIA; TERSIAN, ANA; DO MONTE, FABRICIO

Sand Diego

Conferencia; 2018 SfN Neuroscience; 2018

Society for Neuroscience

The brain ability to identify and discriminate cues associated with reward and aversive stimuli allows an organism to select the most appropriate response. Neurons in the prelimbic prefrontal cortex (PL) can discriminate between cues that anticipate imminent rewards and threats, implicating this region in decision-making under states of certainty. Because PL neurons are critical for the retrieval of reward and fear-associated memories, we speculated that these neurons would also discriminate reward and fear cues under states of uncertainty, when decision-making depends entirely on the associated memories. To address this question, male Long-Evans rats previously implanted with single-unit recording electrodes in PL were trained to learn that each lever press during a cue tone delivered a sucrose pellet in a nearby dish. After training, animals were fear conditioned by pairing a neutral odor with electrical foot shocks. Rats were then tested in a rectangular arena (60cm x 26cm x 40cm) comprising two different zones: a hidden zone and a foraging zone where the lever and the dish were located. The test session was separated in three different phases: only tone cues (reward), only odor cues (fear), or both at the same time (decision-making). To search for food during the decision-making phase, animals had to leave the hidden zone and confront the conditioned odor presented in the foraging zone. During the reward phase, animals pressed the lever in 95% of the tone cue presentations with an average latency to press of 5.3s. During the fear phase, animals showed stronger defensive behaviors characterized by a reduction in time exploring the foraging zone (17% vs. 62% in the reward phase, p=0.0002) and an increase in time spent in the hidden zone (77% vs. 35% in the reward phase, p=0.001). During the decision-making phase, animals showed 66% of reduction in lever presses, with an increase of 49% in the average latency to press. Recordings from PL neurons during the reward phase revealed two distinct populations of responsive neurons that changed their firing rates during the tone cues (Z-score > 2.54 for excitatory and < -1.96 for inhibitory responses, first bin of 300ms). Neurons showing excitatory tone responses during the reward phase continued to respond during the decision-making phase. Interestingly, neurons showing inhibitory tone responses during the reward phase did not respond to the cues during the decision-making phase. Together, our findings suggest that PL inhibitory responses to reward cues are involved in action selection during competing behavioral alternatives (searching for food vs. avoiding potential threats) that depend on previously associated memories.