A systematic review of auditory fear conditioning protocols: Animal models and auditory conditioning stimulus

Abstract

The specific circuits used to investigate fear response have been described on the basis of Pavlovian conditioning or classical fear conditioning procedures. However, prior studies did not utilize identical methods, featuring differences in animal models and exposure tones. This study aimed to identify the most frequently employed animal model and exposure tone that can be feasibly implemented to obtain consistent results in fear conditioning studies. This systematic review analyzed studies on auditory conditioning stimuli effects, i.e., fear conditioning responses, synaptic transmission, synaptic plasticity, long-term potentiation, and associative fear memory, published between 2011 and 2016. Twenty-two studies fulfilled the selection criteria of the analysis. The animal models used were mice (54.5% of studies, with C57BL/6 mice being utilized in 91.7% of the mouse studies) or rats (45.5% of studies, with Sprague–Dawley rats being utilized in 70% of the rat studies). The ranges of loudness, frequency, and duration of tone exposure in the studies were 65–100 dB, 1–12.5 kHz, and 10–30 s, respectively. The most commonly used animal in fear conditioning studies using genetic variation to elucidate certain pathogeneses or therapeutic mechanisms of drugs was the C57BL/6 mouse, whereas Sprague–Dawley rats were frequently used in studies of the physiological responses to auditory fear conditioning, fear memory, synaptic transmission, synaptic plasticity, and associative learning. Significant variation of the tone exposure was also noted.