Changes in CM and CAP with sedation and temperature in the guinea pig: facts and interpretation

Abstract

The influence of xylazine on the amplitude, latency and waveform of VIIIth nerve compound action potential (CAP) and cochlear microphonic (CM) in response to clicks at 95 dB SPL in normal awake preimplanted guinea pigs was investigated. The animals' temperature was monitored but no thermoregulation was exerted, except in one control experiment. Following a 0.2 ml injection of xylazine, CM showed minor variations while CAP audiograms for tone pips between 0.5 and 25 kHz remained normal. However, a progressive decrease in temperature and a strongly correlated increase in CAP amplitude and in N1 and N2 latencies were noticed. For peak N1 the changes were equivalent to linear amplitude and time expansions, and could be reproduced through CAP synthesis with convolution methods using time expanded unit response model and firing density functions. All changes were maximal after 2 h of sedation and recovered within approximately another 2 h. Whereas xylazine is known to induce hypothermia, all the changes disappeared if the animal was thermoregulated. Therefore the changes are interpreted as a result of hypothermia. The mechanism of N1 latency lengthening and increase in amplitude during hypothermia can be understood as a simultaneous increase in spike duration, hair cell/nerve synaptic delay and postsynaptic time constant. This hypothesis yielded a theoretical temperature coefficient for N1 latency (−52 μs/°C) matching that measured experimentally (−55 μs/°C). When compared with peak N1, peak N2 appeared relatively more expanded. Arguments about the origin of N2 are discussed.