Septal and Hippocampal Neurons Contribute to Auditory Relay and Fear Conditioning

Abstract

The hippocampus has been thought to process auditory information. However, the properties, pathway, and role of hippocampal auditory responses are unclear. With loose-patch recordings, we found that hippocampal neurons are mainly responsive to noise and are not tonotopically organized. Their latencies are shorter than those of primary auditory cortical (A1) neurons but longer than those of medial septal (MS) neurons, suggesting that hippocampal auditory information comes from MS neurons rather than from A1 neurons. Silencing the MS blocks both hippocampal auditory responses and memory of auditory fear conditioning trained with noise and tone. Auditory fear conditioning was associated with some cues but not with a specific frequency of sound, as demonstrated by animals trained with noise, 2.5-, 5-, 10-, 15-, or 30-kHz tones, and tested with these sounds. Therefore, the noise responses of hippocampal neurons have identified a population of neurons that can be associated with auditory fear conditioning.

An Emergent Discriminative Learning Is Elicited During Multifrequency Testing

“…Mice were injected with sodium pentobarbital (60–70 mg/kg, i.p., Sigma, United States) and atropine sulfate (0.25 mg/kg, s.c., Nandao, Hainan, China) for anesthesia and inhibition of respiratory secretions, respectively (Xiong et al, 2013; Xiao et al, 2018). Anesthesia was maintained by supplemental doses (13 mg/kg) of pentobarbital throughout the experimental protocol, ensuring a complete lack of the hind paw withdrawal reflex.…”

“…The auditory delay fear conditioning was performed in the behavioral chamber (chamber A) (Habitest, Coulbourn Instruments, Holliston, MA, United States). Details of the apparatus have been previously described (Xiao et al, 2018). The conditioning chamber was cleaned with 70% ethanol, and the bedding material was replaced between the sessions.…”

“…In the single frequency testing, mice were placed in the testing chamber (chamber B). Details of chamber B were the same as in our previous experiments (Xiao et al, 2018). Mice were tested to pure tones of a single frequency individually.…”

“…The freezing response in animals induced by fear conditioning is independent of the auditory CS frequency used in the conditioning (Laxmi et al, 2003; Antunes and Moita, 2010; Park et al, 2016; Xiao et al, 2018). After training with single frequency pure tones, using pure tones of different frequencies for testing could cause a similar fear response in animals (Xiao et al, 2018).…”

“…The freezing response in animals induced by fear conditioning is independent of the auditory CS frequency used in the conditioning (Laxmi et al, 2003; Antunes and Moita, 2010; Park et al, 2016; Xiao et al, 2018). After training with single frequency pure tones, using pure tones of different frequencies for testing could cause a similar fear response in animals (Xiao et al, 2018). However, auditory fear conditioning could elicit CS-specific modifications of auditory evoked potentials (AEPs) in A1 (Leon et al, 2017) and best frequency (BF) shifts in the lemniscal auditory system toward the frequency of the conditioned tone (Gao and Suga, 2000; Ji and Suga, 2003, 2007; Suga, 2012).…”