Granular subdivision of retrosplenial cortex (A29) is critically required for retrieval of contextual threatening memories.

DE OLMOS S; ERIC L. SIGWALD; ALFREDO LORENZO

Congreso; Annual Meeting, Society for Neuroscience; 2019

Session 242 - Learning and Memory: Cortical-Hippocampal Interactions I242.17 / W40 - Granular subdivision of retrosplenial cortex (A29) is critically required for retrieval of contextual threatening memoriesAuthors: *S. DE OLMOS, E. SIGWALD, A. LORENZO;Inst. de Investigacion Medica Mercedes y Martin Ferreyra-INIMEC-CONICET-Universidad Nacional de Cordoba, Cordoba, ArgentinaAbstract: The contribution of the retrosplenial cortex (RSC) to contextual fear memory (CFM) is increasingly recognized, however the role of the granular (area 29, A29) and dysgranular (area 30, A30) subdivisions of the RSC remains elusive. Here, we performed comprehensive behavioral studies to dissect the contribution of A29 to CFM retrieval. To that end, orchiectomized (ORC) and intact male rats received an intraperitoneal (I.P.) injection of saline (control) or 5mg/Kg MK801 after training and memory formation. Previously, we showed that in orchiectomized (ORC), but not in intact male rats, this MK801 treatment induces overt loss of neurons selectively in layers IV-Va of A29 (A29MK801 neurons), and impairs freezing expression during CFM retrieval (Sigwald et al., Brain Struct Funct 2016). Here, we show that, compared to ORC-saline, ORC-MK801 rats showed impaired CFM retrieval in an A-B-A design for contextual-fear conditioning (ANOVA F(1,29) = 3.6834, p=0.004); however, context discrimination was not affected. In ORC animals, neither novel object recognition (ANOVA F(1,14)=0.00002, p = 0.996) and object-in-context discrimination (ANOVA F(1,11)=0.63115, p = 0.44) were impaired by MK801, further indicating that loss of A29MK801 neurons do not affect contextual discrimination. Elevated plus maze test showed that anxiety-like behavior was not affected in ORC-MK801 animals (ANOVA F(1,12)=0.2498, p = 0.6262), suggesting that loss of A29MK801 neurons does not affect the emotional state that could impair freezing during test. Importantly, in a sensory preconditioning test (ANOVA (F(1,17)=4.7184), MK801 treatment abolished higher order CFM retrieval in ORC, but not in intact male rats; which indicates that loss of A29MK801 neurons severely impairs higher order memory retrieval. Collectively, our data provides the first evidence indicating that neurons in layers IV-Va of A29 are critically required for the retrieval of an associative memory, however are dispensable for context discrimination or modulating the emotional state of the animal. The anatomofunctional mechanism by which A29MK801 neurons could participate in CFM retrieval will be discussed.Grant Support: FONCYT-PICT 2014-3155; SECYT-Universidad Nacional de Cordoba