Rapid and Lasting Effects of Activating BDNF-Expressing PVH Neurons on Energy Balance.

Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), are implicit in causing obesity. Mutations that reduce BDNF and TrkB expression are associated with obesity in humans and mice. Recently, it was reported that gene deletion in the neurons of the paraventricular hypothalamus (PVH) caused positive energy balance and severe obesity in the form of hyperphagia, impaired adaptive thermogenesis, and decreased energy expenditure.

Direct Anandamide Activation of TRPV1 Produces Divergent Calcium and Current Responses.

In the brainstem nucleus of the solitary tract (NTS), primary vagal afferent neurons express the transient receptor potential vanilloid subfamily member 1 (TRPV1) at their central terminals where it contributes to quantal forms of glutamate release. The endogenous membrane lipid anandamide (AEA) is a putative TRPV1 agonist in the brain, yet the extent to which AEA activation of TRPV1 has a neurophysiological consequence is not well established. We investigated the ability of AEA to activate TRPV1 in vagal afferent neurons in comparison to capsaicin (CAP).

Ethyl Vanillin Activates TRPA1.

The nonselective cation channel transient receptor potential ankryn subtype family 1 (TRPA1) is expressed in neurons of dorsal root ganglia and trigeminal ganglia and also in vagal afferent neurons that innervate the lungs and gastrointestinal tract. Many TRPA1 agonists are reactive electrophilic compounds that form covalent adducts with TRPA1. Allyl isothiocyanate (AITC), the common agonist used to identify TRPA1, contains an electrophilic group that covalently binds with cysteine residues of TRPA1 and confers a structural change on the channel.

Genetic and pharmacological evidence for low-abundance TRPV3 expression in primary vagal afferent neurons.

Primary vagal afferent neurons express a multitude of thermosensitive ion channels. Within this family of ion channels, the heat-sensitive capsaicin receptor (TRPV1) greatly influences vagal afferent signaling by determining the threshold for action-potential initiation at the peripheral endings, while controlling temperature-sensitive forms of glutamate release at central vagal terminals. Genetic deletion of TRPV1 does not completely eliminate these temperature-dependent effects, suggesting involvement of additional thermosensitive ion channels.

Channeling satiation: a primer on the role of TRP channels in the control of glutamate release from vagal afferent neurons.

Obesity results from the chronic imbalance between food intake and energy expenditure. To maintain homeostasis, the brainstem nucleus of the solitary tract (NTS) integrates peripheral information from visceral organs and initiates reflex pathways that control food intake and other autonomic functions. This peripheral-to-central neural communication occurs through activation of vagal afferent neurons which converge to form the solitary tract (ST) and synapse with strong glutamatergic contacts onto NTS neurons.

Isolation of TRPV1 independent mechanisms of spontaneous and asynchronous glutamate release at primary afferent to NTS synapses.

Cranial visceral afferents contained within the solitary tract (ST) contact second-order neurons in the nucleus of the solitary tract (NTS) and release the excitatory amino acid glutamate via three distinct exocytosis pathways; synchronous, asynchronous, and spontaneous release. The presence of TRPV1 in the central terminals of a majority of ST afferents conveys activity-dependent asynchronous glutamate release and provides a temperature sensitive calcium conductance which largely determines the rate of spontaneous vesicle fusion. TRPV1 is present in unmyelinated C-fiber afferents and these facilitated forms of glutamate release may underlie the relative strength of C-fibers in activating autonomic reflex pathways.

Cadherin-6 mediates axon-target matching in a non-image-forming visual circuit.

Neural circuits consist of highly precise connections among specific types of neurons that serve a common functional goal. How neurons distinguish among different synaptic targets to form functionally precise circuits remains largely unknown. Here, we show that during development, the adhesion molecule cadherin-6 (Cdh6) is expressed by a subset of retinal ganglion cells (RGCs) and also by their targets in the brain.

Identification of a subversive substrate of Trichomonas vaginalis purine nucleoside phosphorylase and the crystal structure of the enzyme-substrate complex.

Trichomonas vaginalis is an anaerobic protozoan parasite that causes trichomoniasis, a common sexually transmitted disease with worldwide impact. One of the pivotal enzymes in its purine salvage pathway, purine nucleoside phosphorylase (PNP), shows physical properties and substrate specificities similar to those of the high molecular mass bacterial PNPs but differing from those of human PNP. While carrying out studies to identify inhibitors of T.