The role of synaptic-like vesicles in control of mechanosensation in peripheral nerve terminals

Guy Smith Bewick, Robert Banks

Research output: Contribution to conferenceAbstract

Abstract

Small (50 nm dia), clear vesicles in vertebrate primary mechanosensory nerve terminals were identified by early electron microscopists - at about the same time as in synaptic terminals. This was recognised by Sir Bernard Katz, in Nerve, Muscle and Synapse (1966) but the absence of an obvious mechanosensory function and the keen interest in their role at synapses meant they were largely forgotten. Recently, however, we have become intrigued by the ubiquitous presence of these ‘synaptic-like vesicles’ (SLVs) on the ‘wrong’ side of peripheral mechanosensory nerve/target contacts - i.e. in sensory terminals that receive and transduce mechanosensory stimuli. This includes muscle spindle afferents, hair follicle palisade endings, atrial and aortic baroreceptors, and joint proprioceptors - indeed, any mechanosensory nerve terminals that have been studied ultrastructurally. The resemblance between SLVs and synaptic vesicles is more than simply structural (for original references, see Bewick et al, 2005). Peripheral mechanosensory terminals contain synaptobrevin/VAMP I and II, synapsin I, synaptophysin, the terminal membrane docking protein syntaxin IB, even glutamate and vGlut1. Crucially, function is disrupted by the synaptic neurotoxins tetanus toxin and latrotoxin, and Ca channel blockers. However, there are important differences. SLVs are not ‘synaptic’, since release sites (‘active zones’), if present, are poorly developed and SLVs recycle over the whole terminal surface. We are investigating the role of SLVs in primary mechanosensory terminals, in particular their mechanism of action and their potentially essential importance in controlling the functional expression of the stretch-activated channels in the terminal membrane. We initially used the rat muscle spindle primary endings as a model (Bewick et al, 2005), but the principles uncovered seem essentially the same in the other mechanosensory terminals we have examined - lanceolate terminals of palisade endings of guard hair and vibrissal follicles; and aortic baroreceptors. Evidence will be presented that SLVs undergo endo- and exocytosis, in a Ca-dependent and mechanically modulated manner. We also have evidence they release glutamate which regulates terminal firing by activating an established but highly unusual metabotropic glutamate receptor (mGluR; (Boss et al, 1994; Pellegrini-Giampietro et al, 1996). The mGluR is insensitive to common ionotropic and metabotropic receptor antagonists, but is inhibited by the group I mGluR agonist (R,S) 3,5 DHPG and a selective antagonist, PCCG-13 (Pellicciari et al, 1999). Indeed, receptor inhibition alone can totally block mechanically evoked output. In the hippocampus, the mGluR activates phospholipase D (Pellegrini-Giampietro et al, 1996), so we term it the PLD-mGluR, pending official characterisation. The data indicate SLVs recycle tonically, releasing glutamate, while mechanical activity increases recycling. The antagonist pharmacology suggests endogenous glutamate release acts through a non-canonical, PLD-mGluR to maintain excitability in these sensory endings. This glutamatergic system, therefore, may be a ubiquitous autogenic modulator of mechanosensory peripheral terminals, powerfully modulating the mechanically-evoked output of the transduction process, between total abolition and a doubling of afferent firing.
Original languageEnglish
Publication statusPublished - 2010
EventPhysiological Society Cross-Themed Meeting - Durham, United Kingdom
Duration: 15 Dec 201017 Dec 2010

Conference

ConferencePhysiological Society Cross-Themed Meeting
CountryUnited Kingdom
CityDurham
Period15/12/1017/12/10

Fingerprint

Synaptic Vesicles
Peripheral Nerves
Glutamic Acid
Muscle Spindles
Pressoreceptors
Hair Follicle
Synapses
R-SNARE Proteins
Synapsins
Qa-SNARE Proteins
Tetanus Toxin
Phospholipase D
Synaptophysin
Metabotropic Glutamate Receptors
Exocytosis
Presynaptic Terminals
Neurotoxins
Recycling
Endocytosis
Vertebrates

Cite this

Bewick, G. S., & Banks, R. (2010). The role of synaptic-like vesicles in control of mechanosensation in peripheral nerve terminals. Abstract from Physiological Society Cross-Themed Meeting, Durham, United Kingdom.

The role of synaptic-like vesicles in control of mechanosensation in peripheral nerve terminals. / Bewick, Guy Smith; Banks, Robert.

2010. Abstract from Physiological Society Cross-Themed Meeting, Durham, United Kingdom.

Research output: Contribution to conferenceAbstract

Bewick, GS & Banks, R 2010, 'The role of synaptic-like vesicles in control of mechanosensation in peripheral nerve terminals' Physiological Society Cross-Themed Meeting, Durham, United Kingdom, 15/12/10 - 17/12/10, .
Bewick GS, Banks R. The role of synaptic-like vesicles in control of mechanosensation in peripheral nerve terminals. 2010. Abstract from Physiological Society Cross-Themed Meeting, Durham, United Kingdom.
Bewick, Guy Smith ; Banks, Robert. / The role of synaptic-like vesicles in control of mechanosensation in peripheral nerve terminals. Abstract from Physiological Society Cross-Themed Meeting, Durham, United Kingdom.
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abstract = "Small (50 nm dia), clear vesicles in vertebrate primary mechanosensory nerve terminals were identified by early electron microscopists - at about the same time as in synaptic terminals. This was recognised by Sir Bernard Katz, in Nerve, Muscle and Synapse (1966) but the absence of an obvious mechanosensory function and the keen interest in their role at synapses meant they were largely forgotten. Recently, however, we have become intrigued by the ubiquitous presence of these ‘synaptic-like vesicles’ (SLVs) on the ‘wrong’ side of peripheral mechanosensory nerve/target contacts - i.e. in sensory terminals that receive and transduce mechanosensory stimuli. This includes muscle spindle afferents, hair follicle palisade endings, atrial and aortic baroreceptors, and joint proprioceptors - indeed, any mechanosensory nerve terminals that have been studied ultrastructurally. The resemblance between SLVs and synaptic vesicles is more than simply structural (for original references, see Bewick et al, 2005). Peripheral mechanosensory terminals contain synaptobrevin/VAMP I and II, synapsin I, synaptophysin, the terminal membrane docking protein syntaxin IB, even glutamate and vGlut1. Crucially, function is disrupted by the synaptic neurotoxins tetanus toxin and latrotoxin, and Ca channel blockers. However, there are important differences. SLVs are not ‘synaptic’, since release sites (‘active zones’), if present, are poorly developed and SLVs recycle over the whole terminal surface. We are investigating the role of SLVs in primary mechanosensory terminals, in particular their mechanism of action and their potentially essential importance in controlling the functional expression of the stretch-activated channels in the terminal membrane. We initially used the rat muscle spindle primary endings as a model (Bewick et al, 2005), but the principles uncovered seem essentially the same in the other mechanosensory terminals we have examined - lanceolate terminals of palisade endings of guard hair and vibrissal follicles; and aortic baroreceptors. Evidence will be presented that SLVs undergo endo- and exocytosis, in a Ca-dependent and mechanically modulated manner. We also have evidence they release glutamate which regulates terminal firing by activating an established but highly unusual metabotropic glutamate receptor (mGluR; (Boss et al, 1994; Pellegrini-Giampietro et al, 1996). The mGluR is insensitive to common ionotropic and metabotropic receptor antagonists, but is inhibited by the group I mGluR agonist (R,S) 3,5 DHPG and a selective antagonist, PCCG-13 (Pellicciari et al, 1999). Indeed, receptor inhibition alone can totally block mechanically evoked output. In the hippocampus, the mGluR activates phospholipase D (Pellegrini-Giampietro et al, 1996), so we term it the PLD-mGluR, pending official characterisation. The data indicate SLVs recycle tonically, releasing glutamate, while mechanical activity increases recycling. The antagonist pharmacology suggests endogenous glutamate release acts through a non-canonical, PLD-mGluR to maintain excitability in these sensory endings. This glutamatergic system, therefore, may be a ubiquitous autogenic modulator of mechanosensory peripheral terminals, powerfully modulating the mechanically-evoked output of the transduction process, between total abolition and a doubling of afferent firing.",
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T1 - The role of synaptic-like vesicles in control of mechanosensation in peripheral nerve terminals

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N2 - Small (50 nm dia), clear vesicles in vertebrate primary mechanosensory nerve terminals were identified by early electron microscopists - at about the same time as in synaptic terminals. This was recognised by Sir Bernard Katz, in Nerve, Muscle and Synapse (1966) but the absence of an obvious mechanosensory function and the keen interest in their role at synapses meant they were largely forgotten. Recently, however, we have become intrigued by the ubiquitous presence of these ‘synaptic-like vesicles’ (SLVs) on the ‘wrong’ side of peripheral mechanosensory nerve/target contacts - i.e. in sensory terminals that receive and transduce mechanosensory stimuli. This includes muscle spindle afferents, hair follicle palisade endings, atrial and aortic baroreceptors, and joint proprioceptors - indeed, any mechanosensory nerve terminals that have been studied ultrastructurally. The resemblance between SLVs and synaptic vesicles is more than simply structural (for original references, see Bewick et al, 2005). Peripheral mechanosensory terminals contain synaptobrevin/VAMP I and II, synapsin I, synaptophysin, the terminal membrane docking protein syntaxin IB, even glutamate and vGlut1. Crucially, function is disrupted by the synaptic neurotoxins tetanus toxin and latrotoxin, and Ca channel blockers. However, there are important differences. SLVs are not ‘synaptic’, since release sites (‘active zones’), if present, are poorly developed and SLVs recycle over the whole terminal surface. We are investigating the role of SLVs in primary mechanosensory terminals, in particular their mechanism of action and their potentially essential importance in controlling the functional expression of the stretch-activated channels in the terminal membrane. We initially used the rat muscle spindle primary endings as a model (Bewick et al, 2005), but the principles uncovered seem essentially the same in the other mechanosensory terminals we have examined - lanceolate terminals of palisade endings of guard hair and vibrissal follicles; and aortic baroreceptors. Evidence will be presented that SLVs undergo endo- and exocytosis, in a Ca-dependent and mechanically modulated manner. We also have evidence they release glutamate which regulates terminal firing by activating an established but highly unusual metabotropic glutamate receptor (mGluR; (Boss et al, 1994; Pellegrini-Giampietro et al, 1996). The mGluR is insensitive to common ionotropic and metabotropic receptor antagonists, but is inhibited by the group I mGluR agonist (R,S) 3,5 DHPG and a selective antagonist, PCCG-13 (Pellicciari et al, 1999). Indeed, receptor inhibition alone can totally block mechanically evoked output. In the hippocampus, the mGluR activates phospholipase D (Pellegrini-Giampietro et al, 1996), so we term it the PLD-mGluR, pending official characterisation. The data indicate SLVs recycle tonically, releasing glutamate, while mechanical activity increases recycling. The antagonist pharmacology suggests endogenous glutamate release acts through a non-canonical, PLD-mGluR to maintain excitability in these sensory endings. This glutamatergic system, therefore, may be a ubiquitous autogenic modulator of mechanosensory peripheral terminals, powerfully modulating the mechanically-evoked output of the transduction process, between total abolition and a doubling of afferent firing.

AB - Small (50 nm dia), clear vesicles in vertebrate primary mechanosensory nerve terminals were identified by early electron microscopists - at about the same time as in synaptic terminals. This was recognised by Sir Bernard Katz, in Nerve, Muscle and Synapse (1966) but the absence of an obvious mechanosensory function and the keen interest in their role at synapses meant they were largely forgotten. Recently, however, we have become intrigued by the ubiquitous presence of these ‘synaptic-like vesicles’ (SLVs) on the ‘wrong’ side of peripheral mechanosensory nerve/target contacts - i.e. in sensory terminals that receive and transduce mechanosensory stimuli. This includes muscle spindle afferents, hair follicle palisade endings, atrial and aortic baroreceptors, and joint proprioceptors - indeed, any mechanosensory nerve terminals that have been studied ultrastructurally. The resemblance between SLVs and synaptic vesicles is more than simply structural (for original references, see Bewick et al, 2005). Peripheral mechanosensory terminals contain synaptobrevin/VAMP I and II, synapsin I, synaptophysin, the terminal membrane docking protein syntaxin IB, even glutamate and vGlut1. Crucially, function is disrupted by the synaptic neurotoxins tetanus toxin and latrotoxin, and Ca channel blockers. However, there are important differences. SLVs are not ‘synaptic’, since release sites (‘active zones’), if present, are poorly developed and SLVs recycle over the whole terminal surface. We are investigating the role of SLVs in primary mechanosensory terminals, in particular their mechanism of action and their potentially essential importance in controlling the functional expression of the stretch-activated channels in the terminal membrane. We initially used the rat muscle spindle primary endings as a model (Bewick et al, 2005), but the principles uncovered seem essentially the same in the other mechanosensory terminals we have examined - lanceolate terminals of palisade endings of guard hair and vibrissal follicles; and aortic baroreceptors. Evidence will be presented that SLVs undergo endo- and exocytosis, in a Ca-dependent and mechanically modulated manner. We also have evidence they release glutamate which regulates terminal firing by activating an established but highly unusual metabotropic glutamate receptor (mGluR; (Boss et al, 1994; Pellegrini-Giampietro et al, 1996). The mGluR is insensitive to common ionotropic and metabotropic receptor antagonists, but is inhibited by the group I mGluR agonist (R,S) 3,5 DHPG and a selective antagonist, PCCG-13 (Pellicciari et al, 1999). Indeed, receptor inhibition alone can totally block mechanically evoked output. In the hippocampus, the mGluR activates phospholipase D (Pellegrini-Giampietro et al, 1996), so we term it the PLD-mGluR, pending official characterisation. The data indicate SLVs recycle tonically, releasing glutamate, while mechanical activity increases recycling. The antagonist pharmacology suggests endogenous glutamate release acts through a non-canonical, PLD-mGluR to maintain excitability in these sensory endings. This glutamatergic system, therefore, may be a ubiquitous autogenic modulator of mechanosensory peripheral terminals, powerfully modulating the mechanically-evoked output of the transduction process, between total abolition and a doubling of afferent firing.

M3 - Abstract

ER -