Post-training load-related changes of auditory working memory: An EEG study

Working memory (WM) refers to the temporary retention and manipulation of information, and its capacity is highly susceptible to training. Yet, the neural mechanisms that allow for increased performance under demanding conditions are not fully understood. We expected that post-training efficiency in WM performance modulates neural processing during high load tasks. We tested this hypothesis, using electroencephalography (EEG) (N = 39), by comparing source space spectral power of healthy adults performing low and high load auditory WM tasks. Prior to the assessment, participants either underwent a modality-specific auditory WM training, or a modality-irrelevant tactile WM training, or were not trained (active control). After a modality-specific training participants showed higher behavioral performance, compared to the control. EEG data analysis revealed general effects of WM load, across all training groups, in the theta-, alpha-, and beta-frequency bands. With increased load theta-band power increased over frontal, and decreased over parietal areas. Centro-parietal alpha-band power and central beta-band power decreased with load. Interestingly, in the high load condition a tendency toward reduced beta-band power in the right medial temporal lobe was observed in the modality-specific WM training group compared to the modality-irrelevant and active control groups. Our finding that WM processing during the high load condition changed after modality-specific WM training, showing reduced beta-band activity in voice-selective regions, possibly indicates a more efficient maintenance of task-relevant stimuli. The general load effects suggest that WM performance at high load demands involves complementary mechanisms, combining a strengthening of task-relevant and a suppression of task-irrelevant processing

VTA neurons coordinate with the hippocampal reactivation of spatial experience

Spatial learning requires the hippocampus, and the replay of spatial sequences during hippocampal sharp wave-ripple (SPW-R) events of quiet wakefulness and sleep is believed to play a crucial role. To test whether the coordination of VTA reward prediction error signals with these replayed spatial sequences could contribute to this process, we recorded from neuronal ensembles of the hippocampus and VTA as rats performed appetitive spatial tasks and subsequently slept. We found that many reward responsive (RR) VTA neurons coordinated with quiet wakefulness-associated hippocampal SPW-R events that replayed recent experience. In contrast, coordination between RR neurons and SPW-R events in subsequent slow wave sleep was diminished. Together, these results indicate distinct contributions of VTA reinforcement activity associated with hippocampal spatial replay to the processing of wake and SWS-associated spatial memory.National Institutes of Health (U.S.) (Grant R01-MH061976)United States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant N00014-10-1-0936)National Institutes of Health (U.S.) (Mentored Grant K08-MH-81207-01A1

Micro-drive Array for Chronic in vivo Recording: Drive Fabrication

Chronic recording of large populations of neurons is a valuable technique for studying the function of neuronal circuits in awake behaving rats. Lightweight recording devices carrying a high density array of tetrodes allow for the simultaneous monitoring of the activity of tens to hundreds of individual neurons. Here we describe a protocol for the fabrication of a micro-drive array with twenty one independently movable micro-drives. This device has been used successfully to record from hippocampal and cortical neurons in our lab. We show how to prepare a custom designed, 3-D printed plastic base that will hold the micro-drives. We demonstrate how to construct the individual micro-drives and how to assemble the complete micro-drive array. Further preparation of the drive array for surgical implantation, such as the fabrication of tetrodes, loading of tetrodes into the drive array and gold-plating, is covered in a subsequent video article

Micro-drive Array for Chronic in vivo Recording: Tetrode Assembly

The tetrode, a bundle of four electrodes, has proven to be a valuable tool for the simultaneous recording of multiple neurons in-vivo. The differential amplitude of action potential signatures over the channels of a tetrode allows for the isolation of single-unit activity from multi-unit signals. The ability to precisely control the stereotaxic location and depth of the tetrode is critical for studying coordinated neural activity across brain regions. In combination with a micro-drive array, it is possible to achieve precise placement and stable control of many tetrodes over the course of days to weeks. In this protocol, we demonstrate how to fabricate and condition tetrodes using basic tools and materials, install the tetrodes into a multi-drive tetrode array for chronic in-vivo recording in the rat, make ground wire connections to the micro-drive array, and attach a protective cone onto the micro-drive array in order to protect the tetrodes from physical contact with the environment

Dispatched Homolog 2 is targeted by miR-214 through a combination of three weak microRNA recognition sites

MicroRNAs (miRNAs) regulate gene expression by inhibiting translation of target mRNAs through pairing with miRNA recognition elements (MREs), usually in 3′ UTRs. Because pairing is imperfect, identification of bona fide mRNA targets presents a challenge. Most target recognition algorithms strongly emphasize pairing between nucleotides 2–8 of the miRNA (the ‘seed’ sequence) and the mRNA but adjacent sequences and the local context of the 3′ UTR also affect targeting. Here, we show that dispatched 2 is a target of miR-214. In zebrafish, dispatched 2 is expressed in the telencephalon and ventral hindbrain and is essential for normal zebrafish development. Regulation of dispatched 2 by miR-214 is via pairing with three, noncanonical, weak MREs. By comparing the repression capacity of GFP reporters containing different dispatched 2 sequences, we found that a combination of weak sites, which lack canonical seed pairing, can effectively target an mRNA for silencing. This finding underscores the challenge that prediction algorithms face and emphasizes the need to experimentally validate predicted MREs

Multiple Transient Signals in Human Visual Cortex Associated with an Elementary Decision

The cerebral cortex continuously undergoes changes in its state, which are manifested in transient modulations of the cortical power spectrum. Cortical state changes also occur at full wakefulness and during rapid cognitive acts, such as perceptual decisions. Previous studies found a global modulation of beta-band (12–30 Hz) activity in human and monkey visual cortex during an elementary visual decision: reporting the appearance or disappearance of salient visual targets surrounded by a distractor. The previous studies disentangled neither the motor action associated with behavioral report nor other secondary processes, such as arousal, from perceptual decision processing per se. Here, we used magnetoencephalography in humans to pinpoint the factors underlying the beta-band modulation. We found that disappearances of a salient target were associated with beta-band suppression, and target reappearances with beta-band enhancement. This was true for both overt behavioral reports (immediate button presses) and silent counting of the perceptual events. This finding indicates that the beta-band modulation was unrelated to the execution of the motor act associated with a behavioral report of the perceptual decision. Further, changes in pupil-linked arousal, fixational eye movements, or gamma-band responses were not necessary for the beta-band modulation. Together, our results suggest that the beta-band modulation was a top-down signal associated with the process of converting graded perceptual signals into a categorical format underlying flexible behavior. This signal may have been fed back from brain regions involved in decision processing to visual cortex, thus enforcing a “decision-consistent” cortical state

Pneumococcal Gene Complex Involved in Resistance to Extracellular Oxidative Stress

Streptococcus pneumoniae is a Gram-positive bacterium which is a member of the normal human nasopharyngeal flora but can also cause serious disease such as pneumonia, bacteremia, and meningitis. Throughout its life cycle, S. pneumoniae is exposed to significant oxidative stress derived from endogenously produced hydrogen peroxide (H2O2) and from the host through the oxidative burst. How S. pneumoniae, an aerotolerant anaerobic bacterium that lacks catalase, protects itself against hydrogen peroxide stress is still unclear. Bioinformatic analysis of its genome identified a hypothetical open reading frame belonging to the thiol-specific antioxidant (TlpA/TSA) family, located in an operon consisting of three open reading frames. For all four strains tested, deletion of the gene resulted in an approximately 10-fold reduction in survival when strains were exposed to external peroxide stress. However, no role for this gene in survival of internal superoxide stress was observed. Mutagenesis and complementation analysis demonstrated that all three genes are necessary and sufficient for protection against oxidative stress. Interestingly, in a competitive index mouse pneumonia model, deletion of the operon had no impact shortly after infection but was detrimental during the later stages of disease. Thus, we have identified a gene complex involved in the protection of S. pneumoniae against external oxidative stress, which plays an important role during invasive disease.

Joubert syndrome: genotyping a Northern European patient cohort

Joubert syndrome (JBS) is a rare neurodevelopmental disorder belonging to the group of ciliary diseases. JBS is genetically heterogeneous, with >20 causative genes identified to date. A molecular diagnosis of JBS is essential for prediction of disease progression and genetic counseling. We developed a targeted next-generation sequencing (NGS) approach for parallel sequencing of 22 known JBS genes plus 599 additional ciliary genes. This method was used to genotype a cohort of 51 well-phenotyped Northern European JBS cases (in some of the cases, Sanger sequencing of individual JBS genes had been performed previously). Altogether, 21 of the 51 cases (41%) harbored biallelic pathogenic mutations in known JBS genes, including 14 mutations not previously described. Mutations in C5orf42 (12%), TMEM67 (10%), and AHI1 (8%) were the most prevalent. C5orf42 mutations result in a purely neurological Joubert phenotype, in one case associated with postaxial polydactyly. Our study represents a population-based cohort of JBS patients not enriched for consanguinity, providing insight into the relative importance of the different JBS genes in a Northern European population. Mutations in C5orf42 are relatively frequent (possibly due to a Dutch founder mutation) and mutations in CEP290 are underrepresented compared with international cohorts. Furthermore, we report a case with heterozygous mutations in CC2D2A and B9D1, a gene associated with the more severe Meckel–Gruber syndrome that was recently published as a potential new JBS gene, and discuss the significance of this finding