# Presynaptic Terminal Proteins and Nicotinic Receptors Are Depleted from Mouse Parasympathetic Ganglionic Junctions Paralysed with Botulinum Neurotoxin Type A

## TL;DR

This study shows that botulinum toxin A causes a rapid decline in key proteins at mouse parasympathetic synapses, leading to prolonged paralysis.

## Contribution

The study reveals novel insights into the depletion of presynaptic and nicotinic receptor proteins following botulinum toxin exposure.

## Key findings

- Botulinum neurotoxin type A caused rapid depletion of synaptic vesicle markers and nicotinic receptors in parasympathetic junctions.
- Synaptic function and protein expression remained depressed for 4 weeks, with recovery taking over 8 weeks.
- Postsynaptic proteins at nearby neuromuscular junctions remained stable, contrasting with parasympathetic synapse changes.

## Abstract

Plasticity is fundamental to the development, strengthening, and maintenance of healthy synaptic connections and recovery from injury in both the central and peripheral nervous systems. Yet, the processes involved are poorly understood. Herein, using a combination of patch-clamp electrophysiology and immuno-fluorescence confocal microscopy in adult mice, it is shown that blockade of synaptic transmission at submandibular ganglion junctions exposed to botulinum neurotoxin type A was accompanied by a rapid and striking decline in the abundance of synaptic vesicle markers—SV2, vesicle-associated membrane protein 2, and vesicular acetylcholine transporter—plus SNAP-25 (cleaved and intact) and postsynaptic α7 nicotinic acetylcholine receptors. Such alterations by the neurotoxin of parasympathetic synapses contrast starkly with the stability of postsynaptic proteins at nearby skeletal neuromuscular junctions. Both neurotransmission and the expression of SV2 and α7 nicotinic acetylcholine receptors remained depressed for 4 weeks, with full recovery of synaptic function delayed for more than 8 weeks. These novel findings may explain the relatively slow recovery of autonomic function after botulism or following therapeutic injections to alleviate hypersecretory disorders.