Plappert C F, Pilz P K, Becker K, Becker C M, Schnitzler H U
Universität Tübingen, Tierphysiologie Zoologisches Institut, Morgenstelle 28, D-72076 Tubingen, Germany.
Behav Brain Res. 2001 Jun;121(1-2):57-67. doi: 10.1016/s0166-4328(00)00385-5.
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.
自发性突变小鼠痉挛（spd）携带一个错义突变，该突变影响甘氨酸受体α1亚基基因。这导致对甘氨酸的结合亲和力降低。spd突变体表现出夸张的听觉惊吓反应（ASR）。本研究旨在阐明这种增强的ASR是由于听觉处理的改变，还是由于运动系统去抑制导致更强的运动输出，或者是由于对惊吓通路的调节影响发生变化，即习惯化和敏感化的潜在机制发生变化。我们发现，在纯合spd/spd突变体中，惊吓阈值较低，记录的输入/输出（i/o）函数斜率更陡，该斜率反映了感觉输入与运动输出之间的关系。在重复呈现高声压级（SPL）惊吓刺激（高于惊吓阈值25 dB）期间，spd/spd突变体的ASR幅度不像野生型那样降低。相反，当呈现低声压级惊吓刺激时，ASR幅度降低。在高声压级惊吓刺激后施加的足部电击并未像在野生型中那样导致spd/spd突变体的ASR幅度进一步增加。在杂合spd/+突变体中，所有这些参数都介于spd/spd突变体和野生型小鼠之间，但更接近野生型。spd/spd突变体中i/o函数更陡的斜率可能是由感觉输入增加和运动输出增加共同导致的。然而，重复刺激期间ASR幅度的改变过程以及额外足部电击敏感化的缺陷，只能通过spd/spd突变体中更高的敏感化水平来解释。根据“双过程理论”，高声压级惊吓刺激引起的强烈敏感化可能会抵消习惯化，导致ASR幅度持续保持较高水平。此外，额外的足部电击敏感化也受到抑制。敏感化水平的提高可能是由于听觉处理的改变导致高声压级惊吓刺激的敏感化作用更强。或者，野生型中对敏感化结构（如杏仁核）的甘氨酸能紧张性抑制在spd/spd突变体中可能会减弱，从而导致较高的敏感化水平。
