The effects of moderate prenatal alcohol exposure on performance in hippocampal-sensitive spatial memory and anxiety tasks by adult male and female rat offspring.

Moderate prenatal alcohol exposure (mPAE) results in structural alterations to the hippocampus. Previous studies have reported impairments in hippocampal-sensitive tasks, but have not compared performance between male and female animals. In the present study, performance in hippocampal-sensitive spatial memory and anxiety behavior tests were compared across adult male and female saccharin (SACC) control mPAE Long-Evans rat offspring. Two tests of spatial memory were conducted that were aimed at assessing memory for recently acquired spatial information: A delayed spatial alternation task using an M-shaped maze and a delayed match-to-place task in the Morris water task. In both tasks, rats in SACC and mPAE groups showed similar learning and retention of a spatial location even after a 2-h interval between encoding and retention. A separate group of adult male and female SACC and mPAE rat offspring were tested for anxiety-like behaviors in the elevated plus-maze paradigm. In this test, both male and female mPAE rats exhibited a significantly greater amount of time and a greater number of head dips in the open arms, while locomotion and open arm entries did not differ between groups. The results suggest that mPAE produces a reduction in anxiety-like behaviors in both male and female rats in the elevated plus-maze.

Acosta G ，Rico KT ，Madden JT ，LaCour A ，Wang E ，Sanchez LM ，Davies S ，Maestas-Olguin C ，Cox KB ，Reyna NC ，Hogeveen J ，Savage DD ，Pentkowski NS ，Clark BJ ... -  《-》

The effects of moderate prenatal alcohol exposure on performance in object and spatial discrimination tasks by adult male rats.

Exposure to alcohol during pregnancy produces Fetal Alcohol Spectrum Disorders, which in its most severe form is characterized by physical dysmorphology and neurobehavioral alterations. Moderate prenatal alcohol exposure (mPAE) is known to produce deficits in discrimination of spatial locations in adulthood. However, the impact of mPAE on higher-order sensory representations, such as discrimination of perceptually similar stimuli, is currently unknown. In the present study, we tested the hypothesis that mPAE would disrupt performance on hippocampal-sensitive tasks that require discrimination between perceptually similar objects or discrimination between spatial locations in a radial arm maze. Here we report that male mPAE rats exhibited intact performance on three types of object discrimination tasks: one in which rats discriminated between distinct toy objects, a second in which discrimination was made between distinct and similar LEGO objects, and a mnemonic similarity task in which rats discriminated between randomly presented LEGO objects that varied in similarity with a learned object. Although adult male mPAE rats performed similarly to control rats on all three object discrimination tasks, they showed deficits when tested in a radial arm maze spatial discrimination task. Specifically, male mPAE rats expressed a significantly higher number of working memory errors (returns to previously visited arms) and were more likely to use non-spatial strategies during training. Together, the findings of the present study support the conclusion that mPAE produces specific deficits in the online processing of spatial information and executing spatial navigation strategies, but spares the ability to discriminate between perceptually similar stimuli.

Sanchez LM ，Acosta G ，Cushing SD ，Johnson SA ，Turner SM ，Davies S ，Savage DD ，Burke SN ，Clark BJ ... -  《-》

Late-term moderate prenatal alcohol exposure impairs tactile, but not spatial, discrimination in a T-maze continuous performance task in juvenile rats.

Existing maze apparatuses used in rodents often exclusively assess spatial discriminability as a means to evaluate learning impairments. Spatial learning in such paradigms is reportedly spared by moderate prenatal alcohol exposure in rats, suggesting that spatial reinforcement alone is insufficient to delineate executive dysfunction, which consistently manifests in humans prenatally-exposed to alcohol. To address this, we designed a single-session continuous performance task in the T-maze apparatus that requires rats to discriminate within and between simultaneously-presented spatial (left or right) and tactile (sandpaper or smooth) stimuli for food reinforcement across four sequential discrimination stages: simple discrimination, intradimensional reversal 1, extradimensional shift, and intradimensional reversal 2. This design incorporates elements of working memory, attention, and goal-seeking behavior which collectively contribute to the executive function construct. Here, we found that rats prenatally-exposed to alcohol performed worse in both the tactile intradimensional reversal and extradimensional shift; alternatively, rats prenatally-exposed to alcohol acquired the extradimensional shift faster when shifting from the tactile to spatial dimension. In line with previous work, moderate prenatal alcohol exposure spared specifically spatial discrimination in this paradigm. However, when tactile stimuli were mapped into the spatial dimension, rats prenatally-exposed to alcohol required more trials to discriminate between the dimensions. We demonstrate that tactile stimuli can be operantly employed in a continuous performance T-maze task to detect discriminatory learning impairments in rats exposed to moderate prenatal alcohol. The current paradigm may be useful for assessing features of executive dysfunction in rodent models of fetal alcohol spectrum disorders.

Bailey CS ，Craig AJ ，Jagielo-Miller JE ，Leibold CT ，Keller PS ，Beckmann JS ，Prendergast MA ... -  《-》

Impact of parental ethanol exposure on offspring memory: Sex differences in spatial and passive avoidance tasks.

The impact of parental alcohol exposure on subsequent generations recently gained significant attention. Ethanol, widely consumed by humans, is known for its anxiolytic effects upon initial use. However, repeated ethanol consumption leads to cognitive dysfunction, dependence, and other physical abnormalities. In line with recent publications from our group, this study investigated the role of parental ethanol exposure-10 days prior to gestation-on learning and memory, which are critical cognitive abilities, in male and female offspring. Adult male and female Wistar rats (n = 12) were exposed to ethanol (in drinking water) for 30 days, followed by a 10-day ethanol-free period. Each rat was then paired to mate with either an ethanol-naïve (control, n = 12) or ethanol-exposed rat, resulting in four distinct groups: (1) control male and female, (2) ethanol-exposed male and control female (P.EE), (3) ethanol-exposed female and control male (M.EE), and (4) ethanol-exposed male and female (P + M.EE). Adult male and female offspring were tested for spatial learning and memory (Morris Water Maze) and passive avoidance memory. Additionally, brain-derived neurotrophic factor (BDNF) levels in the cerebrospinal fluid were evaluated. Results showed that spatial memory was negatively affected by parental ethanol consumption in both male and female offspring, while spatial learning was impaired only in female offspring of ethanol-exposed dams. In the passive avoidance paradigm, memory retrieval was impaired in ethanol-exposed male offspring, whereas in females, only the P + M.EE group showed a deficit in memory retention. While BDNF levels decreased in male offspring, an enhancement in BDNF was observed in female offspring of the P. EE group. In conclusion, our findings suggest that parental ethanol exposure before conception has differential impacts on learning and memory, depending on the offspring's sex and the type of memory tested. Spatial memory was affected in both sexes (except for females in the P. EE group), while memory retrieval in the passive avoidance task remained unaffected in female offspring of the P. EE and M. EE groups. Conversely, male offspring of ethanol-exposed sires and dams exhibited deficits in passive avoidance memory. This may suggest that in memory tasks involving inhibitory cues, such as passive avoidance, female offspring of ethanol-exposed dams or sires are more resilient to memory deficits compared to male offspring. This resilience could possibly be attributed to their higher anxiety levels relative to males.

Heidari A ，Hajikarim-Hamedani A ，Asefi M ，Soltani H ，Zamani MS ，Ghane Y ，Rassa S ，Sadat-Shirazi M ，Zarrindast MR ... -  《-》

Effects of Blocking Multiple Sources of Calcium in Hippocampus During Spatial Learning and Memory Using a Rapid Acquisition Variant of the Morris Water Task.

Long-term potentiation (LTP) is proposed to be the molecular mechanism underlying learning and memory in the brain. A key event for LTP is the influx of calcium into post-synaptic neurons via multiple ion channel control systems. One such system involves N-methyl-D-aspartate receptors (NMDARs), which were originally believed to be essential for LTP and new learning. Recent studies have demonstrated that hippocampal NMDARs are critical for learning new spatial information in a novel environment; however, when pre-training occurs prior to new spatial learning, these receptors are not needed. Additionally, researchers have shown that activation of voltage-gated calcium channels (VGCCs) and their associated calcium influx can induce LTP independent of NMDARs. These findings led to the idea that the amount of calcium required for learning in hippocampus depends on whether the new learning takes place in a novel or familiar environment, with a novel environment demanding greater calcium influx. It was hypothesized that to impair new learning in a familiar environment both NMDARs and VGCCs would need to be blocked. Long-Evans rats were trained in a three-phase version of the Morris water task, which included pre-training, new learning mass-training, and a probe test. Prior to mass-training, intrahippocampal VGCCs were blocked individually or in combination with NMDARs blockade to evaluate their effects on the rats learning and memory. The results showed that blocking both NMDARs and VGCCs simultaneously impaired new spatial learning with familiar information, whereas VGCC blockade alone did not.

Diaz CR ，Hong NS ，Dyck K ，Gibb MJ ，Panjwani M ，Szymanski K ，McDonald RJ ... -  《-》