Spaced training enhances memory and prefrontal ensemble stability in mice.

It is commonly acknowledged that memory is substantially improved when learning is distributed over time, an effect called the "spacing effect". So far it has not been studied how spaced learning affects the neuronal ensembles presumably underlying memory. In the present study, we investigate whether trial spacing increases the stability or size of neuronal ensembles. Mice were trained in the "everyday memory" task, an appetitive, naturalistic, delayed matching-to-place task. Spacing trials by 60 min produced more robust memories than training with shorter or longer intervals. c-Fos labeling and chemogenetic inactivation established the involvement of the dorsomedial prefrontal cortex (dmPFC) in successful memory storage. In vivo calcium imaging of excitatory dmPFC neurons revealed that longer trial spacing increased the similarity of the population activity pattern on subsequent encoding trials and upon retrieval. Conversely, trial spacing did not affect the size of the total neuronal ensemble or the size of subpopulations dedicated to specific task-related behaviors and events. Thus, spaced learning promotes reactivation of prefrontal neuronal ensembles processing episodic-like memories.

Join the Lone Kidney Club: incentivising live organ donation.

Given the dramatic shortage of transplantable organs, demand cannot be met by established and envisioned organ procurement policies targeting postmortem donation. Live organ donation (LOD) is a medically attractive option, and ethically permissible if informed consent is given and donor beneficence balances recipient non-maleficence. Only a few legal and regulatory frameworks incentivise LOD, with the key exception of Israel's Organ Transplant Law, which has produced significant improvements in organ donation rates. Therefore, I propose an organ procurement system that incentivises LOD by allocating additional priority points to the living donor on any transplant waiting list. I outline benefits and challenges for potential recipients, donors and society at large, and suggest measures to ensure medical protection of marginalised patient groups.

Benchmarking miniaturized microscopy against two-photon calcium imaging using single-cell orientation tuning in mouse visual cortex.

Miniaturized microscopes are lightweight imaging devices that allow optical recordings from neurons in freely moving animals over the course of weeks. Despite their ubiquitous use, individual neuronal responses measured with these microscopes have not been directly compared to those obtained with established in vivo imaging techniques such as bench-top two-photon microscopes. To achieve this, we performed calcium imaging in mouse primary visual cortex while presenting animals with drifting gratings. We identified the same neurons in image stacks acquired with both microscopy methods and quantified orientation tuning of individual neurons. The response amplitude and signal-to-noise ratio of calcium transients recorded upon visual stimulation were highly correlated between both microscopy methods, although influenced by neuropil contamination in miniaturized microscopy. Tuning properties, calculated for individual orientation tuned neurons, were strongly correlated between imaging techniques. Thus, neuronal tuning features measured with a miniaturized microscope are quantitatively similar to those obtained with a two-photon microscope.

Food and water restriction lead to differential learning behaviors in a head-fixed two-choice visual discrimination task for mice.

Head-fixed behavioral tasks can provide important insights into cognitive processes in rodents. Despite the widespread use of this experimental approach, there is only limited knowledge of how differences in task parameters, such as motivational incentives, affect overall task performance. Here, we provide a detailed methodological description of the setup and procedures for training mice efficiently on a two-choice lick left/lick right visual discrimination task. We characterize the effects of two distinct restriction regimens, i.e. food and water restriction, on animal wellbeing, activity patterns, task acquisition, and performance. While we observed reduced behavioral activity during the period of food and water restriction, the average animal discomfort scores remained in the 'sub-threshold' and 'mild' categories throughout the experiment, irrespective of the restriction regimen. We found that the type of restriction significantly influenced specific aspects of task acquisition and engagement, i.e. the number of sessions until the learning criterion was reached and the number of trials performed per session, but it did not affect maximum learning curve performance. These results indicate that the choice of restriction paradigm does not strongly affect animal wellbeing, but it can have a significant effect on how mice perform in a task.

Optogenetic dissection of medial prefrontal cortex circuitry.

The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and hippocampus), the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.