J Chem Neuroanat 2023 Mar 01;128:102209. doi: 10.1016/j.jchemneu.2022.102209.

Inactivation of the dorsal CA1 hippocampus impairs the consolidation of discriminative avoidance memory by modulating the intrinsic and extrinsic hippocampal circuitry.

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Despite progress in understanding the role of the dorsal hippocampus in the acquisition, consolidation and retrieval of episodic-like memory, plastic changes within the intra- and extrahippocampal circuits for aversive memory formation and anxiety-like behaviours must still be identified since both processes contribute to multiple aspects of flexible decision-making. Here, we investigated the effect of reversible inactivation induced by a muscimol microinfusion into the dorsal CA1 subfield (dCA1) either prior to acquisition or to retrieval testing of a discriminative avoidance task performed in a plus-maze apparatus (PM-DAT). Differential cAMP-response-element-binding protein 1 (CREB-1) expression in the dorsal and ventral CA1 and CA3 of the hippocampus (dCA1, dCA3, vCA1, and vCA3), dorsal dentate gyrus (dDG), and infralimbic (IL) and prelimbic (PrL) regions of the medial prefrontal cortex was also assessed to investigate the molecular changes associated with the consolidation or retrieval of episodic-like memory and anxiety. Adult male Wistar rats were assigned to two control groups, learning (no surgery/no microinfusion, n = 7) and sham-operated (sham surgery/no microinfusion, n = 6) groups, or four experimental groups, in which the vehicle (0.5 µl per side, n = 8/per group) or a GABAA receptor agonist (0.5 µg/0.5 µl muscimol/per side) was bilaterally microinfused in the dCA1 30 min prior to training (n = 9) or prior to testing sessions (n = 6) with a 24 h intertrial interval. Memory was evaluated using the percentage of time spent in the nonaversive enclosed arms, whereas anxiety was measured by calculating the percentages of time spent and entries into open arms and the percentage of time spent self-grooming. Our findings corroborated previous data showing that the dCA1 is required for discriminative avoidance consolidation. Furthermore, additional information indicated that impaired long-term memory was associated with downregulated CREB-1 expression in the dDG and vCA3. Moreover, memory retrieval was not impaired by dCA1 inactivation prior to the testing session, which was associated with the upregulation of CREB-1 in the dCA3 and vCA1 and downregulation in the dCA1 and vCA3. Differential expression of CREB was not identified in the IL or PrL areas. These results improve our understanding of how the hippocampal circuitry mediates the acquisition and retrieval of aversive memory and anxiety.

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