A 35-year-old farmer from rural Maharashtra presents with severe muscle rigidity, trismus, and risus sardonicus 10 days after sustaining a deep puncture wound to his foot while working in the field. The structure marked **B** in the diagram represents the molecular target of tetanospasmin at inhibitory interneurons. Which of the following best describes the pathophysiological consequence of tetanospasmin's action on this structure?

Explanation

## Why "Cleavage of synaptobrevin prevents GABA and glycine release from spinal interneurons, leading to unopposed motor neuron firing and spastic paralysis" is right Tetanospasmin is a zinc-dependent endopeptidase that specifically cleaves synaptobrevin (VAMP), a SNARE protein essential for synaptic vesicle fusion and exocytosis. By blocking this mechanism at inhibitory (GABAergic and glycinergic) interneurons in the spinal cord, the toxin prevents the release of inhibitory neurotransmitters. This allows motor neurons to fire without inhibitory control, resulting in the characteristic spastic paralysis, trismus (lockjaw), risus sardonicus, and opisthotonus seen in tetanus. This is the exact mechanism described in Murray's Microbiology and KD Tripathi's Pharmacology. ## Why each distractor is wrong - **Blockade of acetylcholine receptors at the neuromuscular junction causes flaccid paralysis and loss of deep tendon reflexes**: This describes botulinum toxin's mechanism at the NMJ, which also cleaves SNARE proteins but at a different location (NMJ), producing flaccid paralysis—the opposite clinical picture from tetanus. Tetanospasmin acts on spinal interneurons, not the NMJ. - **Inhibition of acetylcholinesterase leads to excessive acetylcholine accumulation and muscle fasciculations**: This is the mechanism of organophosphate poisoning or anticholinesterase agents (e.g., physostigmine), not tetanospasmin. Tetanus does not involve ACh accumulation. - **Degradation of motor neuron cell bodies results in progressive denervation atrophy**: This describes poliomyelitis or motor neuron disease, not tetanus. Tetanospasmin does not destroy motor neurons; it disrupts inhibitory signaling, causing unopposed excitation. **High-Yield:** Tetanus = spastic paralysis (unopposed excitation from blocked inhibition); Botulism = flaccid paralysis (blocked ACh release at NMJ). Both use SNARE cleavage, but different sites and opposite clinical outcomes. [cite: Murray 9e; KD Tripathi 9e Ch 33; Park 26e]