Increased sensitization of acoustic startle response in spasmodic mice with a mutation of the glycine receptor alpha1-subunit gene.
The spontaneous mutant mouse spasmodic (spd) carries a missense mutation affecting the glycine receptor alpha1-subunit gene. This results in a decreased binding affinity to glycine. Spd mutants show exaggerated acoustic startle responses (ASR). The present study sought to elucidate whether this increased ASR is due to a changed auditory processing or to stronger motor output resulting from a disinhibited motor system or, alternatively, to changes in modulatory influences on the startle pathway, namely in the mechanisms underlying habituation and sensitization. We found that in homozygous spd/spd mutants the startle threshold was lower, and the recorded slope of input/output (i/o) function, which reflects the relation between sensory input and motor output, was steeper. During repetitive presentation of high sound pressure level (SPL) startle stimuli (25 dB above startle threshold), ASR amplitudes did not decrease in spd/spd mutants as they do in the wildtype. In contrast, ASR amplitudes decreased when low SPL startle stimuli were presented. Footshocks presented after high SPL startle stimuli did not cause a further increase in ASR amplitudes of spd/spd mutants as in the wildtype. In heterozygous spd/+ mutants all these parameters were between those of spd/spd mutants and wildtype mice but closer to those of the wildtype. The steeper slope of i/o function in spd/spd mutants may be caused by both an increased sensory input and an increased motor output. The altered course of ASR amplitudes during repetitive stimulation and the deficit in additional footshock sensitization, however, can only be explained by an increased sensitization level in the spd/spd mutants. In accordance with the "dual process theory" strong sensitization evoked by high SPL startle stimuli supposedly counteracts habituation, leading to a constant high ASR amplitude. Furthermore, additional footshock sensitization is prevented. The increased sensitization level may be due to a change in auditory processing leading to a stronger sensitizing effect of the startle stimuli with high SPL. Alternatively, glycinergic tonic inhibition of sensitizing structures (e.g. the amygdala) in the wildtype may be diminished in spd/spd mutants, thus leading to a high sensitization level.
Plappert
C F
CF
Universität Tübingen, Tierphysiologie Zoologisches Institut, Morgenstelle 28, D-72076 Tubingen, Germany. claudia.plappert@uni-tuebingen.de
Pilz
P K
PK
Becker
K
K
Becker
C M
CM
Schnitzler
H U
HU
D000161:Acoustic Stimulation; D000818:Animals; D001143:Arousal / Q000235:genetics*; D004597:Electroshock; D005239:Fear / Q000502:physiology; D005260:Female; D005838:Genotype; D006185:Habituation, Psychophysiologic / Q000502:physiology; D006579:Heterozygote; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D018009:Receptors, Glycine / Q000235:genetics*; D013216:Reflex, Startle / Q000502:physiology*
D018009:Receptors, Glycine