Reactivated memories can be modified during reconsolidation, making this process a potential therapeutic target for posttraumatic stress disorder (PTSD), a mental illness characterized by the recurring avoidance of situations that evoke trauma-related fears. However, avoidance memory reconsolidation depends on a set of still loosely defined boundary conditions, limiting the translational value of basic research. In particular, the involvement of the hippocampus in fear-motivated avoidance memory reconsolidation remains controversial. Combining behavioral and electrophysiological analyses in male Wistar rats, we found that previous learning of relevant nonaversive information is essential to elicit the participation of the hippocampus in avoidance memory reconsolidation, which is associated with an increase in theta- and gamma-oscillation power and cross-frequency coupling in dorsal CA1 during reactivation of the avoidance response. Our results indicate that the hippocampus is involved in memory reconsolidation only when reactivation results in contradictory representations regarding the consequences of avoidance and suggest that robust nesting of hippocampal theta-gamma rhythms at the time of retrieval is a specific reconsolidation marker. Posttraumatic stress disorder (PTSD) is characterized by maladaptive avoidance responses to stimuli or behaviors that represent or bear resemblance to some aspect of a traumatic experience. Disruption of reconsolidation, the process by which reactivated memories become susceptible to modifications, is a promising approach for treating PTSD patients. However, much of what is known about fear-motivated avoidance memory reconsolidation derives from studies based on fear conditioning instead of avoidance-learning paradigms. Using a step-down inhibitory avoidance task in rats, we found that the hippocampus is involved in memory reconsolidation only when the animals acquired the avoidance response in an environment that they had previously learned as safe and showed that increased theta- and gamma-oscillation coupling during reactivation is an electrophysiological signature of this process.

The mesocorticolimbic dopaminergic system includes the ventral tegmental area (VTA) and its projections to the amygdala (AMY), the hippocampus (HIP) and the medial prefrontal cortex (mPFC), among others. Object recognition (OR) long-term memory (LTM) processing requires dopaminergic activity but, although some of the brain regions mentioned above are necessary for OR LTM consolidation, their possible dopamine-mediated interplay remains to be analyzed. Using adult male Wistar rats, we found that posttraining microinjection of the dopamine D1/D5 receptor antagonist SCH23390 in mPFC or AMY, but not in HIP, impaired OR LTM. The dopamine D2 receptor agonist quinpirole had no effect on retention. VTA inactivation also hindered OR LTM, and even though this effect was unaffected by co-infusion of the dopamine D1/D5 receptor agonist SKF38393 in HIP, mPFC or AMY alone, it was reversed by simultaneous activation of D1/D5 receptors in the last two regions. Our results demonstrate that the mesocorticolimbic dopaminergic system is indeed essential for OR LTM consolidation and suggest that the role played by some of its components during this process is much more complex than previously thought.

We investigated the effect of the intra-CA1 administration of the D1/D5 receptor antagonist SCH23390 and the D1/D5 receptor agonist SKF38393 on spatial memory in the water maze. When given immediately, but not 3h after training, SCH23390 hindered long-term spatial memory formation without affecting non-spatial memory or the normal functionality of the hippocampus. On the contrary, post-training infusion of SKF38393 enhanced retention and facilitated the spontaneous recovery of the original spatial preference after reversal learning. Our findings demonstrate that hippocampal D1/D5 receptors play an essential role in spatial memory processing.