A possible role of medial Prefrontal Cortex 5-HT2aR in the resolution of memory trace interference during retrieval

PEDRO BEKINSCHTEIN; NOELIA WEISSTAUB

Huerta Grande

Congreso; Primera Reunion Conjunta de Neurociencias; 2009

Sociedad Argentina de Neurociencias

The medial pre frontal cortex (mPFC) has been involved in several higher order functions including behavioral flexibility, attention, inhibitory control, decision making, goal-directed behaviors, interference and response selection. The interference theory refers to the idea that forgetting occurs because the recall of certain items interferes with the recall of other items. Under this theory, two memory traces that share certain neuronal circuits will trigger the activation of the PFC in order to prevent interference. The result of the mPFC activation would be the subsequent forgetting or supression of one of the traces in favor of the other one. The PFC activity is heavily modulated by different neurotransmitter pathways, including the serotoninergic system. Serotonin (5-HT) modulates different physiological responses including mood, impulsivity, aggression and cognition among others.. It works through the activation of 14 different receptors. In particular, the mPFC expressed high levels of the excitatory 5-HT2a receptor (5-HT2aR), which have been the focus of intense study as a key player in the modulation of cortical activity. Particularly, changes  in cortical 5-HT2aR have been associated with psychiatric disorders like anxiety, stress  and schizophrenia. However it is not clear which is the role of the serotoninergic system and the 5-HT2aR in particular during response selection and interference processes. We studied the possible role of the 5-HT system and the 5-HT2aR in interference processes using different versions of the novel object recognition task (NOR). In all the experiments rats received local injections of the selective 5-HT2aR antagonist, MDL 11,939, 15 minutes before the test phase. Animals injected with MDL 11, 939 showed deficits in a mPFC-dependent version of the NOR (temporal order) with no changes in attention or novelty detection during a single memory trace hippocampus-dependent NOR. To support our hypothesis that activity of mPFC is important for selection of the most relevant response when there is competition of memory traces, we did an object in context recognition test (OIC). We found that also in this case, blockage of the cortical 5-HT2aR prevented the ability of the mPFC to make a suitable response selection, suggesting that the activity of the mPFC is important when there is competition of memory traces to recall the more relevant one.