Involvement of medial prefrontal cortex NMDA and AMPA/kainate glutamate receptors in social recognition memory consolidation.

Social recognition memory (SRM) enables the distinction between familiar and strange conspecifics, a fundamental ability for sociable species, such as rodents and humans. There is mounting evidence that the medial prefrontal cortex plays a prominent role both in shaping social behavior and in recognition memory. Glutamate is the major excitatory neurotransmitter in the brain, and activity of its ionotropic receptors is known to mediate both synaptic plasticity and consolidation of various types of memories. However, whether these receptors are required in the medial prefrontal cortex (mPFC) for SRM consolidation remains elusive. To address this issue, we submitted rats to a social discrimination paradigm, administered infusions of NMDA- and AMPA/kainate-receptors antagonists into the prelimbic (PrL) subdivision of the mPFC at different post-encoding time points and evaluated long-term memory retention twenty-four hours later. We found that blocking NMDA receptors immediately after the sample phase, but not 3 h later, impaired SRM consolidation, whereas the blockade of AMPA/kainate receptors immediately and 3 h, but not 6 h after the sample phase, prevented long-term memory consolidation. These results highlight the importance of the mPFC in social cognition and may contribute towards the understanding of the dysfunctional social information processing that underlies multiple neuropsychiatric disorders.

Modulation of Carbonic Anhydrases Activity in the Hippocampus or Prefrontal Cortex Differentially Affects Social Recognition Memory in Rats.

Growing evidence indicates that brain carbonic anhydrases (CAs) are key modulators in cognition, particularly in recognition and aversive memories. Here we described a role for these enzymes also in social recognition memory (SRM), defined as the ability to identify and recognize a conspecific, a process that is of paramount importance in gregarious species, such as rodents and humans. Male adult Wistar rats were submitted to a social discrimination task and, immediately after the sample phase, received bilateral infusions of vehicle, the CAs activator D-phenylalanine (D-Phen, 50 nmols/side), the CAs inhibitor acetazolamide (ACTZ; 10 nmols/side) or the combination of D-Phen and ACTZ directly in the CA1 region of the dorsal hippocampus or in the medial prefrontal cortex (mPFC). Animals were tested 30 min (short-term memory) or 24 h later (long-term memory). We found that inhibition of CAs with infusion of ACTZ either in the CA1 or in the mPFC impaired short-term SRM and that this effect was completely abolished by the combined infusion of D-Phen and ACTZ. We also found that activation of CAs with D-Phen facilitated the consolidation of long-term SRM in the mPFC but not in CA1. Finally, we show that activation of CAs in CA1 and in the mPFC enhances the persistence of SRM for up to 7 days. In both cases, the co-infusion of ACTZ fully prevented D-Phen-induced procognitive effects. These results suggest that CAs are key modulators of SRM and unveil a differential involvement of these enzymes in the mPFC and CA1 on memory consolidation.