TarBase-v9.0 extends experimentally supported miRNA-gene interactions to cell-types and virally encoded miRNAs.

TarBase is a reference database dedicated to produce, curate and deliver high quality experimentally-supported microRNA (miRNA) targets on protein-coding transcripts. In its latest version (v9.0, https://dianalab.e-ce.uth.gr/tarbasev9), it pushes the envelope by introducing virally-encoded miRNAs, interactions leading to target-directed miRNA degradation (TDMD) events and the largest collection of miRNA-gene interactions to date in a plethora of experimental settings, tissues and cell-types. It catalogues ∼6 million entries, comprising ∼2 million unique miRNA-gene pairs, supported by 37 experimental (high- and low-yield) protocols in 172 tissues and cell-types. Interactions are annotated with rich metadata including information on genes/transcripts, miRNAs, samples, experimental contexts and publications, while millions of miRNA-binding locations are also provided at cell-type resolution. A completely re-designed interface with state-of-the-art web technologies, incorporates more features, and allows flexible and ingenious use. The new interface provides the capability to design sophisticated queries with numerous filtering criteria including cell lines, experimental conditions, cell types, experimental methods, species and/or tissues of interest. Additionally, a plethora of fine-tuning capacities have been integrated to the platform, offering the refinement of the returned interactions based on miRNA confidence and expression levels, while boundless local retrieval of the offered interactions and metadata is enabled.

The developmental changes in intrinsic and synaptic properties of prefrontal neurons enhance local network activity from the second to the third postnatal weeks in mice.

The prefrontal cortex (PFC) is characterized by protracted maturation. The cellular mechanisms controlling the early development of prefrontal circuits are still largely unknown. Our study delineates the developmental cellular processes in the mouse medial PFC (mPFC) during the second and the third postnatal weeks and characterizes their contribution to the changes in network activity. We show that spontaneous inhibitory postsynaptic currents (sIPSC) are increased, whereas spontaneous excitatory postsynaptic currents (sEPSC) are reduced from the second to the third postnatal week. Drug application suggested that the increased sEPSC frequency in mPFC at postnatal day 10 (P10) is due to depolarizing γ-aminobutyric acid (GABA) type A receptor function. To further validate this, perforated patch-clamp recordings were obtained and the expression levels of K-Cl cotransporter 2 (KCC2) protein were examined. The reversal potential of IPSCs in response to current stimulation was significantly more depolarized at P10 than P20 while KCC2 expression is decreased. Moreover, the number of parvalbumin-expressing GABAergic interneurons increases and their intrinsic electrophysiological properties significantly mature in the mPFC from P10 to P20. Using computational modeling, we show that the developmental changes in synaptic and intrinsic properties of mPFC neurons contribute to the enhanced network activity in the juvenile compared with neonatal mPFC.

Sexual dimorphic effects of restraint stress on prefrontal cortical function are mediated by glucocorticoid receptor activation.

Stress, a major regulator and precipitating factor of cognitive and emotional disorders, differentially manifests between males and females. Our aim was to investigate the mechanisms underlying the sexual dimorphic effects of acute restraint stress (RS) on males and females on the function of the prefrontal cortex (PFC). Adult male and female mice were subjected to RS or left in their home-cage (NR), and then tested in the light-dark test followed by the temporal order object recognition (TOR) task. Female mice exhibited increased anxiety-like levels, whereas male mice only showed deficits in the TOR task. When the behavioural tests were conducted 24 hr following restraint stress (RS24), only the reduced performance in the TOR task in male mice persisted. In a different cohort, evoked field excitatory postsynaptic potentials (fEPSPs) were recorded in layer II of acute PFC slices, immediately or 24 hr after RS. Long-term potentiation (LTP) was significantly reduced in RS and RS24 male, but not female, compared with their respective NR group. LTP in PFC slices incubated with corticosterone showed significantly reduced LTP only in males. To determine whether glucocorticoid signalling is implicated in the RS-induced behavioural effects, a different cohort of mice was administered mifepristone, a corticosterone receptor antagonist. Mifepristone administration 1 hr before RS prevented the effects of RS on the TOR task in males, but not anxiety. In conclusion, RS has differential effects on recency memory and anxiety, in males and females, which are partly mediated by the effects of corticosterone signalling on synaptic plasticity.