The anterior retrosplenial cortex is required for short-term object in place recognition memory retrieval: Role of ionotropic glutamate receptors in male and female Long-Evans rats.

The anterior retrosplenial cortex (aRSC) integrates multimodal sensory information into cohesive associative recognition memories. Little is known about how information is integrated during different learning phases (i.e., encoding and retrieval). Additionally, sex differences are observed in performance of some visuospatial memory tasks; however, inconsistent findings warrant more research. We conducted three experiments using the 1-h delay object-in-place (1-h OiP) test to assess recognition memory retrieval in male and female Long-Evans rats. (i) We found both sexes performed equally in three repeated 1-h OiP test sessions. (ii) We showed infusions of a mixture of muscimol/baclofen (GABAA/B receptor agonists) into the aRSC ~15-min prior to the test phase disrupted 1-h OiP in both sexes. (iii) We assessed the role of aRSC ionotropic glutamate receptors in 1-h OiP retrieval using another squad of cannulated rats and confirmed that infusions of either the competitive AMPA/Kainate receptor antagonist CNQX (3 mM) or competitive NMDA receptor antagonist AP-5 (30 mM) (volumes = 0.50 uL/side) significantly impaired 1-h OiP retrieval in both sexes compared to controls. Taken together, findings challenge reported sex differences and clearly establish a role for aRSC ionotropic glutamate receptors in short-term visuospatial recognition memory retrieval. Thus, modulating neural activity in the aRSC may alleviate some memory processing impairments in related disorders.

Evidence for novelty reward cross-cueing in the odor span task in rats: implications for odor-based reward-motivated tasks.

The odor span task (OST) infers working memory capacity (WMC) by requiring rodents to discriminate between previously presented and session-novel odors to obtain a hidden food reward. Here, rats' responses to session-novel odors and food rewards were assessed to determine whether rats use mitigating strategies in the OST. Rats accurately responded to session-novel odors but also reliably responded to the food reward alone and performed at chance when both a session-novel odor and food reward were presented in separate locations. The inclusion of unscented sand in the cups holding the food reward significantly reduced the rats' responses to the food reward alone. Collectively, these results demonstrate the need for rigorous tests of potential mitigating strategies and hold wide implications for rodent odor discrimination-based behavioral tasks.

High-THC Cannabis Smoke Impairs Incidental Memory Capacity in Spontaneous Tests of Novelty Preference for Objects and Odors in Male Rats.

Working memory is an executive function that orchestrates the use of limited amounts of information, referred to as working memory capacity, in cognitive functions. Cannabis exposure impairs working memory in humans; however, it is unclear whether Cannabis facilitates or impairs rodent working memory and working memory capacity. The conflicting literature in rodent models may be at least partly because of the use of drug exposure paradigms that do not closely mirror patterns of human Cannabis use. Here, we used an incidental memory capacity paradigm where a novelty preference is assessed after a short delay in spontaneous recognition-based tests. Either object or odor-based stimuli were used in test variations with sets of identical [identical stimuli test (IST)] and different [different stimuli test (DST)] stimuli (three or six) for low-memory and high-memory loads, respectively. Additionally, we developed a human-machine hybrid behavioral quantification approach which supplements stopwatch-based scoring with supervised machine learning-based classification. After validating the spontaneous IST and DST in male rats, 6-item test versions with the hybrid quantification method were used to evaluate the impact of acute exposure to high-Δ9-tetrahydrocannabinol (THC) or high-CBD Cannabis smoke on novelty preference. Under control conditions, male rats showed novelty preference in all test variations. We found that high-THC, but not high-CBD, Cannabis smoke exposure impaired novelty preference for objects under a high-memory load. Odor-based recognition deficits were seen under both low-memory and high-memory loads only following high-THC smoke exposure. Ultimately, these data show that Cannabis smoke exposure impacts incidental memory capacity of male rats in a memory load-dependent, and stimuli-specific manner.