Comparable performance on a spatial memory task in data collected in the lab and online

Online data collection offers a wide range of benefits including access to larger and more diverse populations, together with a reduction in the experiment cycle. Here we compare performance in a spatial memory task, in which participants had to estimate object locations following viewpoint shifts, using data from a controlled lab-based setting and from an unsupervised online sample. We found that the data collected in a conventional laboratory setting and those collected online produced very similar results, although the online data was more variable with standard errors being about 10% larger than those of the data collected in the lab. Overall, our findings suggest that spatial memory studies using static images can be successfully carried out online with unsupervised samples. However, given the higher variability of the online data, it is recommended that the online sample size is increased to achieve similar standard errors to those obtained in the lab. For the current study and data processing procedures, this would require an online sample 25% larger than the lab sample.

Hippocampal place cell sequences differ during correct and error trials in a spatial memory task

Theta rhythms temporally coordinate sequences of hippocampal place cell ensembles during active behaviors, while sharp wave-ripples coordinate place cell sequences during rest. We investigated whether such coordination of hippocampal place cell sequences is disrupted during error trials in a delayed match-to-place task. As a reward location was learned across trials, place cell sequences developed that represented temporally compressed paths to the reward location during the approach to the reward location. Less compressed paths were represented on error trials as an incorrect stop location was approached. During rest periods of correct but not error trials, place cell sequences developed a bias to replay representations of paths ending at the correct reward location. These results support the hypothesis that coordination of place cell sequences by theta rhythms and sharp wave-ripples develops as a reward location is learned and may be important for the successful performance of a spatial memory task.

Adolescent ethanol exposure decreases cholinergic markers, blunts behaviorally-evoked acetylcholine and increases in apical dendritic branching within the orbital frontal cortex.

During adolescence, heavy binge-like ethanol consumption can lead to frontocortical structural and functional impairments. These impairments are likely driven by adolescence being a critical time point for maturation of brain regions associated with higher-order cognitive functioning. Rodent models of heavy binge-like ethanol exposure show consistent disruptions to the typical development of the prefrontal cortex (PFC). All deep cortical layers receive cholinergic projections that originate from the Nucleus basalis of Meynert (NbM) complex. These cholinergic projections are highly involved in learning, memory, and attention. Adolescent intermittent ethanol exposure (AIE) induces cholinergic dysfunction as a result of an epigenetic suppression of the genes that drive the cholinergic phenotype. The current study used a model of AIE to assess structural and functional changes to the frontal cortex and NbM following binge-like ethanol exposure in adolescence. Western blot analysis revealed long-term disruptions of the cholinergic circuit following AIE: choline acetyltransferase (ChAT) was suppressed in the NbM and vesicular acetylcholine transporter (VAChT) was suppressed in the orbitofrontal cortex (OFC). In vivo microdialysis for acetylcholine efflux during a spatial memory task determined changes in cholinergic modulation within the PFC following AIE. However, AIE spared performance on the spatial memory task and on an operant reversal task. In a second study, Golgi-Cox staining determined that AIE increased apical dendritic complexity in the OFC, with sex influencing whether the increase in branching occurred near or away from the soma. Spine density or maturity was not affected, likely compensating for a disruption in neurotransmitter function following AIE.

BNIP3L/NIX-mediated mitophagy protects against glucocorticoid-induced synapse defects

Stress-induced glucocorticoids disturb mitochondrial bioenergetics and dynamics; however, instead of being removed via mitophagy, the damaged mitochondria accumulate. Therefore, we investigate the role of glucocorticoids in mitophagy inhibition and subsequent synaptic defects in hippocampal neurons, SH-SY5Y cells, and ICR mice. First, we observe that glucocorticoids decrease both synaptic density and vesicle recycling due to suppressed mitophagy. Screening data reveal that glucocorticoids downregulate BNIP3-like (BNIP3L)/NIX, resulting in the reduced mitochondrial respiration function and synaptic density. Notably, we find that glucocorticoids direct the glucocorticoid receptor to bind directly to the PGC1α promoter, downregulating its expression and nuclear translocation. PGC1α downregulation selectively decreases NIX-dependent mitophagy. Consistent with these results, NIX enhancer pre-treatment of a corticosterone-exposed mouse elevates mitophagy and synaptic density in hippocampus, improving the outcome of a spatial memory task. In conclusion, glucocorticoids inhibit mitophagy via downregulating NIX and that NIX activation represents a potential target for restoring synapse function.

The Effect of Strategic Instruction for Categorical Clustering on Preschoolers’ Recall Accuracy

Categorical clustering involves the grouping of stimuli into meaningful categories when encoding or retrieving to-be-learned information during memory tasks. The current study measured the categorical clustering behavior of 40 three- to four-year-olds who completed a spatial memory task requiring them to remove and return toys to their original locations within a box. After completing the spatial memory task without strategic instruction, participants were randomly assigned to receive instructions to categorically cluster while removing (encoding) or returning the toys (retrieval) to the box, or receive no strategic instruction (control). Results showed increases in clustering behaviors following strategic instruction, suggesting that participants were able to successfully produce clustering behavior following instruction to do so. Although instruction to categorically cluster during encoding and retrieval generated a significant increase in clustering behavior when removing and returning the toys to the box, respectively, it only improved recall for those instructed to categorically cluster when retrieving the toy locations. Increased engagement in categorical clustering when encoding the toy locations negatively impacted recall, resulting in a utilization deficiency for participants instructed to remove the toys according to their category membership. No changes in clustering behavior or recall accuracy were observed in the participants who completed the task a second time without strategic instruction. Implications for the current understanding of utilization deficiencies observed among preschoolers and future directions for research are discussed.

cFos Ensembles in the Dentate Gyrus Rapidly Segregate Over Time and do not Form a Stable Map of Space

Mice require several days of training to master the water maze, a spatial memory task for rodents. The hippocampus plays a key role in the formation of spatial and episodic memories, a process that involves the activation of immediate-early genes such as cFos. We trained cFos-reporter mice in the water maze, expecting that consistent spatial behavior would be reflected by consistent cFos patterns across training episodes. Even after extensive training, however, different sets of dentate gyrus (DG) granule cells were activated every day. Suppressing activity in the original encoding ensemble helped mice to learn a novel platform position (reversal learning). Our results suggest that even in a constant environment, cFos+ ensembles in the dorsal DG segregate as a function of time, but become partially reactivated when animals try to access memories of past events.