Characterization of Toxicological and Neurophysiological Effects of Natural Product Based Chromenes to Fall Armyworm, Spodoptera frugiperda

We previously extracted and purified a chromene amide from Amyris texana and found this scaffold is moderately insecticidal and thus, this study aimed to test the insecticidal properties of 13 synthetically derived chromene analogs to the fall armyworm (FAW, Spodoptera frugiperda). Microinjection of chromenes with alcohol or aldehydes substitutions at the meta position on the benzopyran moiety led to moderate toxicity that was approximately 2- to 3-fold less toxic when compared to permethrin, yet microinjection of differently substituted chromenes exhibited little to no toxicity. Similarly, chromenes with alcohol or aldehydes substitutions at the meta position on the benzopyran moiety were among the most toxic chromenes studied through ingested exposure. In addition to acute toxicity, select chromenes significantly increased the percentage of developmental defects upon eclosion that prevented adult moths from being capable of flight, suggesting these compounds alter development. Interestingly, microinjection yielded differing signs of intoxication between alcohol and aldehyde substitutions where the alcohol resulted in flaccid paralysis and lethargy whereas aldehyde led to tonic contractions and hyperactivity. These contrasting signs of intoxication were also observed in electrophysiological assays where alcohol substitutions led to the depression of central neuron firing activity and aldehyde substitutions led to hyperexcitation of central neurons. In summary, the chromene amides led to acute lethality and/or altered developmental trajectories of FAW, yet the high doses required for acute mortality suggest these scaffolds hold relatively little promise for development into FAW-directed insecticides but may represent novel growth regulators for FAW.

Chromatic Induction in Migraine

The human visual system is not a colorimeter. The perceived colour of a region does not only depend on its colour spectrum, but also on the colour spectra and geometric arrangement of neighbouring regions, a phenomenon called chromatic induction. Chromatic induction is thought to be driven by lateral interactions: the activity of a central neuron is modified by stimuli outside its classical receptive field through excitatory–inhibitory mechanisms. As there is growing evidence of an excitation/inhibition imbalance in migraine, we compared chromatic induction in migraine and control groups. As hypothesised, we found a difference in the strength of induction between the two groups, with stronger induction effects in migraine. On the other hand, given the increased prevalence of visual phenomena in migraine with aura, we also hypothesised that the difference between migraine and control would be more important in migraine with aura than in migraine without aura. Our experiments did not support this hypothesis. Taken together, our results suggest a link between excitation/inhibition imbalance and increased induction effects.

Connectomic analysis reveals an interneuron with an integral role in the retinal circuit for night vision

Night vision in mammals depends fundamentally on rod photoreceptors and the well-studied rod bipolar (RB) cell pathway. The central neuron in this pathway, the AII amacrine cell (AC), exhibits a spatially tuned receptive field, composed of an excitatory center and an inhibitory surround, that propagates to ganglion cells, the retina’s projection neurons. The circuitry underlying the surround of the AII, however, remains unresolved. Here, we combined structural, functional and optogenetic analyses of the mouse retina to discover that surround inhibition of the AII depends primarily on a single interneuron type, the NOS-1 AC: a multistratified, axon-bearing GABAergic cell, with dendrites in both ON and OFF synaptic layers, but with a pure ON (depolarizing) response to light. Our study demonstrates generally that novel neural circuits can be identified from targeted connectomic analyses and specifically that the NOS-1 AC mediates long-range inhibition during night vision and is a major element of the RB pathway.

Connectomic analysis reveals an interneuron with an integral role in the retinal circuit for night vision

SummaryThe mammalian rod bipolar (RB) cell pathway is perhaps the best-studied circuit in the vertebrate retina. Its synaptic interactions with other retinal circuits, however, remain unresolved. Here, we combined anatomical and physiological analyses of the mouse retina to discover that the majority of synaptic inhibition to the AII amacrine cell (AC), the central neuron in the RB pathway, is provided by a single interneuron type: a multistratified, axon-bearing GABAergic AC, with dendrites in both ON and OFF synaptic layers, but with a pure ON (depolarizing) response to light. We used the nNOS-CreER mouse retina to confirm the identity of this interneuron as the wide-field NOS-1 AC. Our study demonstrates generally that novel neural circuits can be identified from targeted connectomic analyses and specifically that the NOS-1 AC mediates long-range inhibition during night vision and is a major element of the RB pathway.

Polarity of varicosity initiation in central neuron mechanosensation

Little is known about mechanical regulation of morphological and functional polarity of central neurons. In this study, we report that mechanical stress specifically induces varicosities in the axons but not the dendrites of central neurons by activating TRPV4, a Ca2+/Na+-permeable mechanosensitive channel. This process is unexpectedly rapid and reversible, consistent with the formation of axonal varicosities in vivo induced by mechanical impact in a mouse model of mild traumatic brain injury. In contrast, prolonged stimulation of glutamate receptors induces varicosities in dendrites but not in axons. We further show that axonal varicosities are induced by persistent Ca2+ increase, disassembled microtubules (MTs), and subsequently reversible disruption of axonal transport, and are regulated by stable tubulin-only polypeptide, an MT-associated protein. Finally, axonal varicosity initiation can trigger action potentials to antidromically propagate to the soma in retrograde signaling. Therefore, our study demonstrates a new feature of neuronal polarity: axons and dendrites preferentially respond to physical and chemical stresses, respectively.