GENERATORS OF THE BRAIN-STEM AUDITORY-EVOKED POTENTIAL IN CAT .1. AN EXPERIMENTAL APPROACH TO THEIR IDENTIFICATION

This paper is the first in a series aimed at identifying the cellular generators of the brainstem auditory evoked potential (BAEP) in cats. The approach involves (1) developing experimental procedures for makin g small selective lesions and determining the corresponding changes in BAEP waveforms, (2) identifying brainstem regions involved in BAEP ge neration by examining the effects of lesions on the BAEP and, (3) iden tifying specific cell populations involved by combining the lesion res ults with electrophysiological and anatomical information from other k inds of studies. We created lesions in the lower brainstem by injectin g kainic acid which is generally toxic for neuronal cell bodies but no t for axons and terminals. This first paper describes the justificatio ns for using kainic acid, explains the associated problems, and develo ps a methodology that addresses the main difficulties. The issues and aspects of the specific methods are generally applicable to physiologi cal and anatomical studies using any neurotoxin, as well as to the pre sent BAEP study. The methods chosen involved (1) measuring the BAEP at regular intervals until it reached a post-injection steady state and perfusing the animals with fixative shortly after the last BAEP record ings were made, (2) using objective criteria to distinguish injection- related BAEP changes from unrelated ones, (3) making control injection s to identify effects not due to kainic acid toxicity, (4) verifying t he anatomical and functional integrity of axons in lesioned regions, a nd (5) examining injected brainstems microscopically for cell loss and cellular abnormalities indicating dysfunction, This combination of me thods enabled us to identify BAEP changes which are clearly correlated with lesion locations.