Errorful and errorless learning: The impact of cue–target constraint in learning from errors

The benefits of testing on learning are well described, and attention has recently turned to what happens when errors are elicited during learning: Is testing nonetheless beneficial, or can errors hinder learning? Whilst recent findings have indicated that tests boost learning even if errors are made on every trial, other reports, emphasizing the benefits of errorless learning, have indicated that errors lead to poorer later memory performance. The possibility that this discrepancy is a function of the materials that must be learned-in particular, the relationship between the cues and targets-was addressed here. Cued recall after either a study-only errorless condition or an errorful learning condition was contrasted across cue-target associations, for which the extent to which the target was constrained by the cue was either high or low. Experiment 1 showed that whereas errorful learning led to greater recall for low-constraint stimuli, it led to a significant decrease in recall for high-constraint stimuli. This interaction is thought to reflect the extent to which retrieval is constrained by the cue-target association, as well as by the presence of preexisting semantic associations. The advantage of errorful retrieval for low-constraint stimuli was replicated in Experiment 2, and the interaction with stimulus type was replicated in Experiment 3, even when guesses were randomly designated as being either correct or incorrect. This pattern provides support for inferences derived from reports in which participants made errors on all learning trials, whilst highlighting the impact of material characteristics on the benefits and disadvantages that accrue from errorful learning in episodic memory

Morphology, distribution and phenotype of polycystin kidney disease 2-like 1-positive cerebrospinal fluid contacting neurons in the brainstem of adult mice

The mammalian spinal cord and medulla oblongata harbor unique neurons that remain in contact with the cerebrospinal fluid (CSF-cNs). These neurons were shown recently to express a polycystin member of the TRP channels family (PKD2L1) that potentially acts as a chemo- or mechanoreceptor. Recent studies carried out in young rodents indicate that spinal CSF-cNs express immature neuronal markers that appear to persist even in adult cells. Nevertheless, little is known about the phenotype and morphological properties of medullar CSF-cNs. Using immunohistochemistry and confocal microscopy techniques on tissues obtained from three-month old PKD2L1:EGFP transgenic mice, we analyzed the morphology, distribution, localization and phenotype of PKD2L1(+) CSF-cNs around the brainstem and cervical spinal cord central canal. We show that PKD2L1(+) CSF-cNs are GABAergic neurons with a subependymal localization, projecting a dendrite towards the central canal and an axon-like process running through the parenchyma. These neurons display a primary cilium on the soma and the dendritic process appears to bear ciliary-like structures in contact with the CSF. PKD2L1(+) CSF-cNs present a conserved morphology along the length of the medullospinal central canal with a change in their density, localization and dendritic length according to the rostro-caudal axis. At adult stages, PKD2L1(+) medullar CSF-cNs appear to remain in an intermediate state of maturation since they still exhibit characteristics of neuronal immaturity (DCX positive, neurofilament 160 kDa negative) along with the expression of a marker representative of neuronal maturation (NeuN). In addition, PKD2L1(+) CSF-cNs express Nkx6.1, a homeodomain protein that enables the differentiation of ventral progenitors into somatic motoneurons and interneurons. The present study provides valuable information on the cellular properties of this peculiar neuronal population that will be crucial for understanding the physiological role of CSF-cNs in mammals and their link with the stem cells contained in the region surrounding the medullospinal central canal

Heterochromatin formation via recruitment of DNA repair proteins

Heterochromatin formation and nuclear organization are important in gene regulation and genome fidelity. Proteins involved in gene silencing localize to sites of damage and some DNA repair proteins localize to heterochromatin, but the biological importance of these correlations remains unclear. In this study, we examined the role of double-strand-break repair proteins in gene silencing and nuclear organization. We find that the ATM kinase Tel1 and the proteins Mre11 and Esc2 can silence a reporter gene dependent on the Sir, as well as on other repair proteins. Furthermore, these proteins aid in the localization of silenced domains to specific compartments in the nucleus. We identify two distinct mechanisms for repair protein–mediated silencing—via direct and indirect interactions with Sir proteins, as well as by tethering loci to the nuclear periphery. This study reveals previously unknown interactions between repair proteins and silencing proteins and suggests insights into the mechanism underlying genome integrity