Hippocampal Long-Term Depression in the Presence of Calcium-Permeable AMPA Receptors

The GluA2 subunit of AMPA glutamate receptors (AMPARs) has been shown to be critical for the expression of NMDA receptor (NMDAR)-dependent long-term depression (LTD). However, in young GluA2 knockout (KO) mice, this form of LTD can still be induced in the hippocampus, suggesting that LTD mechanisms may be modified in the presence of GluA2-lacking, Ca2+ permeable AMPARs. In this study, we examined LTD at the CA1 synapse in GluA2 KO mice by using several well-established inhibitory peptides known to block LTD in wild type (WT) rodents. We showed that while LTD in the KO mice is still blocked by the protein interacting with C kinase 1 (PICK1) peptide pepEVKI, it becomes insensitive to the N-ethylmaleimide-sensitive factor (NSF) peptide pep2m. In addition, the effects of actin and cofilin inhibitory peptides were also altered. These results indicate that in the absence of GluA2, LTD expression mechanisms are different from those in WT animals, suggesting that there are multiple molecular processes enabling LTD expression that are adaptable to physiological and genetic manipulations

Increasing the sensitivity of NMR diffusion measurements by paramagnetic longitudinal relaxation enhancement, with application to ribosome–nascent chain complexes

The translational diffusion of macromolecules can be examined non-invasively by stimulated echo (STE) NMR experiments to accurately determine their molecular sizes. These measurements can be important probes of intermolecular interactions and protein folding and unfolding, and are crucial in monitoring the integrity of large macromolecular assemblies such as ribosome–nascent chain complexes (RNCs). However, NMR studies of these complexes can be severely constrained by their slow tumbling, low solubility (with maximum concentrations of up to 10 μM), and short lifetimes resulting in weak signal, and therefore continuing improvements in experimental sensitivity are essential. Here we explore the use of the paramagnetic longitudinal relaxation enhancement (PLRE) agent NiDO2A on the sensitivity of 15N XSTE and SORDID heteronuclear STE experiments, which can be used to monitor the integrity of these unstable complexes. We exploit the dependence of the PLRE effect on the gyromagnetic ratio and electronic relaxation time to accelerate recovery of 1H magnetization without adversely affecting storage on N z during diffusion delays or introducing significant transverse relaxation line broadening. By applying the longitudinal relaxation-optimized SORDID pulse sequence together with NiDO2A to 70S Escherichia coli ribosomes and RNCs, NMR diffusion sensitivity enhancements of up to 4.5-fold relative to XSTE are achieved, alongside ~1.9-fold improvements in two-dimensional NMR sensitivity, without compromising the sample integrity. We anticipate these results will significantly advance the use of NMR to probe dynamic regions of ribosomes and other large, unstable macromolecular assemblies

Investigating the Role of LIMK1 Signaling in PKA-dependent LTP in the Hippocampus

Long-term potentiation (LTP) in the hippocampus is the most extensive form of long-lasting synaptic plasticity and is widely regarded as the cellular basis of memory formation. The canonical NMDA-receptor (NMDAR)-dependent form of LTP can be differentiated into protein kinase A (PKA)-dependent and -independent forms by the spacing between theta burst stimuli (TBS) induction. Key features of PKA-dependent LTP includes insertion of Ca2+ permeable AMPA receptors (CP-AMPARs) and initiation of de novo protein synthesis. However, the molecular mechanisms that elicit these processes remain unknown. Previous studies suggest PKA can regulate LIM-domain kinase (LIMK) 1, but this regulation has not been demonstrated in synaptic plasticity. Using a combination of electrophysiology, genetic mouse models, and pharmacology, I show that CP-AMPAR-dependent LTP requires PKA regardless of TBS spacing. Furthermore, I demonstrate that LIMK1 is required for PKA-dependent LTP. These findings provide insight into the molecular mechanisms underlying LTP and long-term memory formation.M.Sc.2020-03-21 00:00:0

Dead Shrimp Blues: A Global Assessment of Extinction Risk in Freshwater Shrimps (Crustacea: Decapoda: Caridea)

<div><p>We present the first global assessment of extinction risk for a major group of freshwater invertebrates, caridean shrimps. The risk of extinction for all 763 species was assessed using the IUCN Red List criteria that include geographic ranges, habitats, ecology and past and present threats. The Indo-Malayan region holds over half of global species diversity, with a peak in Indo-China and southern China. Shrimps primarily inhabit flowing water; however, a significant subterranean component is present, which is more threatened than the surface fauna. Two species are extinct with a further 10 possibly extinct, and almost one third of species are either threatened or Near Threatened (NT). Threats to freshwater shrimps include agricultural and urban pollution impact over two-thirds of threatened and NT species. Invasive species and climate change have the greatest overall impact of all threats (based on combined timing, scope and severity of threats).</p></div

Extinction risk in the various shrimp families, expressed as a percentage of species richness per family.

<p>Extinction risk in the various shrimp families, expressed as a percentage of species richness per family.</p

Global species richness of freshwater shrimps, based on 713 out of 763 species.

<p>Global species richness of freshwater shrimps, based on 713 out of 763 species.</p

Number of freshwater shrimp species in each threat category, globally and according to biogeographic realm.

<p>Realms are listed in decreasing order according to total threatened number of taxa (CR + EN + VU, as a percentage of total biodiversity minus EX and DD). Note that a species can be found in more than one realm.</p><p>Number of freshwater shrimp species in each threat category, globally and according to biogeographic realm.</p