The atypical 'hippocampal' glutamate receptor coupled to phospholipase D that controls stretch-sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2.

A metabotropic glutamate receptor coupled to phospholipase D (PLD-mGluR) was discovered in the hippocampus over three decades ago. Its pharmacology and direct linkage to PLD activation are well established and indicate it is a highly atypical glutamate receptor. A receptor with the same pharmacology is present in spindle primary sensory terminals where its blockade can totally abolish, and its activation can double, the normal stretch-evoked firing.

Compliance with a law to reduce alcoholic beverage sales and service in Zacatecas, Mexico.

Background: Research on the effects of restricting bar opening hours and alcohol sales in middle-income countries is very limited. We assessed compliance with and possible effects of a law enacted in Zacatecas, Mexico on December 30, 2017 and implemented in 2018 and 2019 that established a 2 AM bar closing time and 10 PM cut-off for alcohol sales by off-premises stores.

Methods: Monthly observations of bars and off-premises stores and alcohol mystery shopping visits from 2018 to early 2020 were conducted to assess compliance with the law.

Piezo Is Essential for Amiloride-Sensitive Stretch-Activated Mechanotransduction in Larval Drosophila Dorsal Bipolar Dendritic Sensory Neurons.

Stretch-activated afferent neurons, such as those of mammalian muscle spindles, are essential for proprioception and motor co-ordination, but the underlying mechanisms of mechanotransduction are poorly understood. The dorsal bipolar dendritic (dbd) sensory neurons are putative stretch receptors in the Drosophila larval body wall. We have developed an in vivo protocol to obtain receptor potential recordings from intact dbd neurons in response to stretch.

Modulating mechanosensory afferent excitability by an atypical mGluR.

Mechanotransduction by proprioceptive sensory organs is poorly understood. Evidence was recently shown that muscle spindle and hair follicle primary afferents (lanceolates) constantly release glutamate from synaptic-like vesicles (SLVs) within the terminals. The secreted glutamate activates a highly unusual metabotropic glutamate receptor (mGluR) to modulate the firing rate (spindles) and SLV recycling (lanceolates).

Synthesis and biological evaluation of (-)-kainic acid analogues as phospholipase D-coupled metabotropic glutamate receptor ligands.

(-)-Kainic acid potently increases stretch-induced afferent firing in muscle spindles, probably acting through a hitherto uncloned phospholipase D (PLD)-coupled mGlu receptor. Structural modification of (-)-kainic acid was undertaken to explore the C-4 substituent effect on the pharmacology related to muscle spindle firing. Three analogues 1a-c were synthesised by highly stereoselective additions of a CF3, a hydride and an alkynyl group to the Re face of the key pyrrolidin-4-one intermediate 5a followed by further structural modifications.

Glutamatergic modulation of synaptic-like vesicle recycling in mechanosensory lanceolate nerve terminals of mammalian hair follicles.

Our aim in the present study was to determine whether a glutamatergic modulatory system involving synaptic-like vesicles (SLVs) is present in the lanceolate ending of the mouse and rat hair follicle and, if so, to assess its similarity to that of the rat muscle spindle annulospiral ending we have described previously. Both types of endings are formed by the peripheral sensory terminals of primary mechanosensory dorsal root ganglion cells, so the presence of such a system in the lanceolate ending would provide support for our hypothesis that it is a general property of fundamental importance to the regulation of the responsiveness of the broad class of primary mechanosensory endings. We show not only that an SLV-based system is present in lanceolate endings, but also that there are clear parallels between its operation in the two types of mechanosensory endings.

Neuromechanical control of locomotion in the rat.

Rodent models are being extensively used to investigate the effects of traumatic injury and develop and assess the mechanisms of repair and regeneration. We present quantitative assessment of two-dimensional (2D) kinematics of overground walking and for the first time three-dimensional (3D) joint angle kinematics of all four limbs during treadmill walking in intact adult female Long-Evans rats. Gait cycle with subphases and intralimb and interlimb cyclograms are presented.