New methods for quantifying rapidity of action potential onset differentiate neuron types

Two new methods for quantifying the rapidity of action potential onset have lower relative standard deviations and better distinguish neuron cell types than current methods. Action potentials (APs) in most central mammalian neurons exhibit sharp onset dynamics. The main views explaining such an abrupt onset differ. Some studies suggest sharp onsets reflect cooperative sodium channels activation, while others suggest they reflect AP backpropagation from the axon initial segment. However, AP onset rapidity is defined subjectively in these studies, often using the slope at an arbitrary value on the phase plot. Thus, we proposed more systematic methods using the membrane potential’s second-time derivative (V¨m) peak width. Here, the AP rapidity was measured for four different cortical and hippocampal neuron types using four quantification methods: the inverse of full-width at the half maximum of the V¨m peak (IFWd2), the inverse of half-width at the half maximum of the V¨m peak (IHWd2), the phase plot slope, and the error ratio method. The IFWd2 and IHWd2 methods show the smallest variation among neurons of the same type. Furthermore, the AP rapidity, using the V¨m peak width methods, significantly differentiates between different types of neurons, indicating that AP rapidity can be used to classify neuron types. The AP rapidity measured using the IFWd2 method was able to differentiate between all four neuron types analyzed. Therefore, the V¨m peak width methods provide another sensitive tool to investigate the mechanisms impacting the AP onset dynamics.

The Synthetic Cannabinoids THJ-2201 and 5F-PB22 Enhance In Vitro CB1 Receptor-Mediated Neuronal Differentiation at Biologically Relevant Concentrations

Recreational use of synthetic cannabinoids (SCs) before and during pregnancy poses a major public health risk, due to the potential onset of neurodevelopmental disorders in the offspring. Herein, we report the assessment of the neurotoxic potential of two commonly abused SCs, THJ-2201 and 5F-PB22, particularly focusing on how they affect neuronal differentiation in vitro. Differentiation ratios, total neurite length, and neuronal marker expression were assessed in NG108-15 neuroblastoma x glioma cells exposed to the SCs at non-toxic, biologically relevant concentrations (≤1 μM), either in acute or repeated exposure settings. Both SCs enhanced differentiation ratios and total neurite length of NG108-15 cells near two-fold compared to vehicle-treated cells, in a CB1R activation-dependent way, as the CB1R blockade with a specific antagonist (SR141718) abrogated SC-induced effects. Interestingly, repeated 5F-PB22 exposure was required to reach effects similar to a single THJ-2201 dose. Cell viability and proliferation, mitochondrial membrane potential, and intracellular ATP levels were also determined. The tested SCs increased mitochondrial tetramethyl rhodamine ethyl ester (TMRE) accumulation after 24 h at biologically relevant concentrations but did not affect any of the other toxicological parameters. Overall, we report firsthand the CB1R-mediated enhancement of neurodifferentiation by 5F-PB22 and THJ-2201 at biologically relevant concentrations.

Lepton Pair Čerenkov Radiation Emitted by Tachyonic Neutrinos: Lorentz-Covariant Approach and IceCube Data

Current experiments do not exclude the possibility that one or more neutrinos are very slightly superluminal or that they have a very small tachyonic mass. Important bounds on the size of a hypothetical tachyonic neutrino mass term are set by lepton pair Čerenkov radiation (LPCR), that is, by the decay channelν→e+e-ν, which proceeds via a virtualZ0boson. Here, we use a Lorentz-invariant dispersion relation which leads to very tight constraints on the tachyonic mass of neutrinos; we also calculate decay and energy loss rates. A possible cutoff seen in the IceCube neutrino spectrum forEν>2 PeV, due to the potential onset of LPCR, is discussed.