NMDA receptor-dependent processes in the medial prefrontal cortex are important for acquisition and the early stage of consolidation during trace, but not delay eyeblink conditioning

Abstract

Permanent lesions in the medial prefrontal cortex (mPFC) affect acquisition of conditioned responses (CRs) during trace eyeblink conditioning and retention of remotely acquired CRs. To clarify further roles of the mPFC in this type of learning, we investigated the participation of the mPFC in mnemonic processes both during and after daily conditioning using local microinfusion of the GABA A receptor agonist muscimol or the NMDA receptor antagonist APV into the rat mPFC. Muscimol infusions into the mPFC before daily conditioning significantly retarded CR acquisition and reduced CR expression if applied after sufficient learning. APV infusion also impaired acquisition of CRs, but not expression of well-learned CRs. When infusions were made immediately after daily conditioning, acquisition of the CR was partially impaired in both the muscimol and APV infusion groups. In contrast, rats that received muscimol infusions 3 h after daily conditioning exhibited improvement in their CR performance comparable to that of the control group. Both the pre-and post-conditioning infusion of muscimol had no effect on acquisition in the delay paradigm. These results suggest that the mPFC participates in both acquisition of a CR and the early stage of consolidation of memory in trace, but not delay eyeblink conditioning by NMDA receptor-mediated operations.

Inverse temporal contributions of the dorsal hippocampus and medial prefrontal cortex to the expression of long-term fear memories

“…The mPFC involvement in trace and contextual fear conditioning following long retention intervals is consistent with recent observations (Takehara-Nishiuchi et al 2005. Bontempi et al (1999) showed that retention of a spatial discrimination is associated with elevated metabolic activity in the DH 5 d following acquisition, whereas activity in this region 25 d following acquisition is significantly attenuated; frontal cortical activity showed an opposite pattern.…”

Systems Consolidation Requires Postlearning Activation of NMDA Receptors in the Medial Prefrontal Cortex in Trace Eyeblink Conditioning

“…(2) Although we chronically infused D-APV to affect systems consolidation, there exists the possibility that interference with cellular consolidation, rather than systems consolidation, caused the impairments we observed in the present experiment. However, the fact that the involvement of NMDA receptors in the mPFC in cellular consolidation is limited to the time when a memory is beginning to be formed (Takehara-Nishiuchi et al, 2005) leads us to reject this possibility. Therefore, the present results suggest that neural processes in the mPFC are required for systems consolidation.…”

Functional Dissociation within the Entorhinal Cortex for Memory Retrieval of an Association between Temporally Discontiguous Stimuli

“…Theoretical models (Hasselmo et al, 2000;Hasselmo and Stern, 2006) have related this function of the entorhinal cortex to its self-sustaining spike activity observed in vitro (Egorov et al, 2002;Tahvildari et al, 2007) and persistent activity during a delay period following stimulus presentation in vivo (Suzuki et al, 1997;Young et al, 1997). Although persistent activity can be observed in both the LEC and MEC (Egorov et al, 2002;Tahvildari et al, 2007), the LEC is more strongly connected with the perirhinal cortex, whose projections mediate highly processed sensory information (Furtak et al, 2007), and with the prelimbic medial prefrontal cortex (Hoover and Vertes, 2007;Agster and Burwell, 2009), which plays a critical role in memory retrieval in trace eyeblink conditioning (Takehara-Nishiuchi et al, 2005;Oswald et al, 2010). Furthermore, these two regions show differential selectivity for spatial versus nonspatial information (Hargreaves et al, 2005).…”