Parkinson’s disease is one of the most common neurodegenerative diseases. Animal models have contributed a large part to our understanding and therapeutics developed for treatment of PD. There are several more exhaustive reviews of literature that provide the initiated insights into the specific models; however a novel synthesis of the basic advantages and disadvantages of different models is much needed. Here we compare both neurotoxin based and genetic models while suggesting some novel avenues in PD modelling. We also highlight the problems faced and promises of all the mammalian models with the hope of providing a framework for comparison of various systems.
Microbial media has undergone several changes since its inception but some key challenges remain. In recent years, there has been exploration of several alternative nutrient sources, both to cater to the specificity in requirement of growth of "fussy microorganisms" and also to reduce costs for large-scale fermentation that is required for biotechnology. Our mini-review explores these developments and also points at lacunas in the present areas of exploration, such as a lack of concerted effort in pH and osmolarity regulation. We hope that our commentary provides direction for future research in microbial media.
In neurons of the medial superior olive (MSO), voltage-gated ion channels control the submillisecond time resolution of binaural coincidence detection, but little is known about their interplay during trains of synaptic activity that would be experienced during auditory stimuli. Here, using modeling and patch-clamp recordings from MSO principal neurons in gerbil brainstem slices, we examined interactions between two major currents controlling subthreshold synaptic integration: a low-voltage-activated potassium current (IK-LVA) and a hyperpolarization-activated cation current (Ih). Both Ih and IK-LVA contributed strongly to the resting membrane conductance and, during trains of simulated EPSPs, exhibited cumulative deactivation and inactivation, respectively. In current-clamp recordings, regular and irregular trains of simulated EPSCs increased input resistance up to 60%, effects that accumulated and decayed (after train) over hundreds of milliseconds. Surprisingly, the mean voltage and peaks of EPSPs increased by only a few millivolts during trains. Using a model of an MSO cell, we demonstrated that the nearly uniform response during modest depolarizing stimuli relied on changes in Ih and IK-LVA, such that their sum remained nearly constant over time. Experiments and modeling showed that, for simplified binaural stimuli (EPSC pairs in a noisy background), spike probability gradually increased in parallel with the increasing input resistance. Nevertheless, the interplay between Ih and IK-LVA helps to maintain a nearly uniform shape of individual synaptic responses, and we show that the time resolution of synaptic coincidence detection can be maintained during trains if EPSC size gradually decreases (as in synaptic depression), counteracting slow increases in excitability.
In sensory circuits of the brain, developmental changes in the expression and modulation of voltage-gated ion channels are a common occurrence, but such changes are often difficult to assign to clear functional roles. We have explored this issue in the binaural neurons of the medial superior olive (MSO), whose temporal precision in detecting the coincidence of binaural inputs dictates the resolution of azimuthal sound localization. We show that in MSO principal neurons of gerbils during the first week of hearing, a hyperpolarization-activated current (Ih) progressively undergoes a 13-fold increase in maximal conductance, a >10-fold acceleration of kinetics, and, most surprisingly, a 30 mV depolarizing shift in the voltage dependence of activation. This period is associated with an upregulation of the hyperpolarization-activated and cyclic nucleotide-gated (HCN) channel subunits HCN1, HCN2, and HCN4 in the MSO, but only HCN1 and HCN4 were expressed strongly in principal neurons.Ihrecorded in nucleated patches from electrophysiologically mature MSO neurons (>P18) exhibited kinetics and an activation range nearly identical to theIhfound in whole-cell recordings before hearing onset. These results indicate that the developmental changes inIhin MSO neurons can be explained predominantly by modulation from diffusible intracellular factors, and not changes in channel subunit composition. The exceptionally large modulatory changes inIh, together with refinements in synaptic properties transform the coding strategy from one of summation and integration to the submillisecond coincidence detection known to be required for transmission of sound localization cues.
Gelling agents are required for formulating both solid and semisolid media, vital for the isolation of microorganisms. Gelatin was the first gelling agent to be discovered but it soon paved the way for agar, which has far superior material qualities. Source depletion, issues with polymerase-chain-reaction and inability to sustain extermophiles etc., necessitate the need of other gelling agents. Many new gelling agents, such as xantham gum, gellan gum, carrageenan, isubgol and guar gum have been formulated, raising the hopes for the growth of previously unculturable microorganisms. We evaluate the progress in the development of gelling agents, with the hope that our synthesis would help accelerate research in the field.