Discriminative auditory fear learning requires both tuned and nontuned auditory pathways to the amygdala

Abstract

The auditory system has two parallel streams in the brain that have been implicated in auditory fear learning. The lemniscal stream has selective neurons that are tonotopically organized and is thought to be important for sound discrimination. The nonlemniscal stream has less selective neurons, which are not tonotopically organized, and is thought to be important for multimodal processing and for several forms of learning. Therefore, it has been hypothesized that the lemniscal, but not the nonlemniscal, pathway supports discriminative fear to auditory cues. To test this hypothesis we assessed the effect of electrolytic lesions to the ventral, or medial, division of the medial geniculate nucleus (MGv or MGm, which correspond, respectively, to the lemniscal and the nonlemniscal auditory pathway to amygdala) on the acquisition, expression and extinction of fear responses in discriminative auditory fear conditioning, where one tone is followed by shock (conditioned stimulus, CS(+)), and another is not (CS(-)). Here we show that with single-trial conditioning control, MGv- and MGm-lesioned male rats acquire nondiscriminative fear of both the CS(+) and the CS(-). However, after multiple-trial conditioning, control rats discriminate between the CS(+) and CS(-), whereas MGv- and MGm-lesioned do not. Furthermore, post-training lesions of MGm, but not MGv, lead to impaired expression of discriminative fear. Finally, MGm-lesioned rats display high levels of freezing to both the CS(+) and CS(-) even after an extinction session to the CS(+). In summary, our findings suggest that the lemniscal pathway is important for discriminative learning, whereas the nonlemniscal is important for negatively regulating fear responses.

Figure 1.

Neural circuit for auditory fear. a, Direct and indirect auditory pathways to the amygdala. Thicker arrows represent major neuronal inputs. b, Coronal sections showing example electrolytic lesions of the thalamic nuclei (for a schematic representation of the extent of the lesions see supplemental Fig. 1, available at www.jneurosci.org as supplemental material). A1, Primary auditory cortex; A2, secondary auditory cortex.

Figure 2.

Each pathway is sufficient for the acquisition of generalized fear. a, Schematic showing experimental protocol. b, Freezing responses to CS⁺ and CS⁻ during discrimination test. Freezing responses are presented as percentage freezing normalized to baseline freezing levels (for raw data see supplemental Fig. 2, available at www.jneurosci.org as supplemental material). Data are presented as mean ± SEM for n = 24 animals (control, n = 11; MGv-lesion, n = 8; MGm-lesion, n = 5).

Figure 3.

Both pathways are necessary for the acquisition of discriminative fear. a, Schematic showing experimental protocol. b, Freezing responses to CS⁺ and CS⁻ during discrimination test. Freezing responses are presented as percentage freezing normalized to baseline freezing levels (for raw data see supplemental Fig. 3, available at www.jneurosci.org as supplemental material). Data are presented as mean ± SEM for n = 25 animals (control, n = 14; MGv-lesion, n = 7; MGm-lesion, n = 5). *p < 0.0167.

Figure 4.

MGm, but not the MGv, is necessary for the expression of discriminative fear and for extinction of fear to the CS⁺. a, Schematic showing experimental protocol. b, Freezing responses to CS⁺ and CS⁻ during discrimination test, after lesion. c, Freezing responses to CS⁺ and CS⁻ during discrimination test, after extinction session. Freezing responses are presented as percentage freezing normalized to baseline freezing levels (for raw data see supplemental Fig. 4, available at www.jneurosci.org as supplemental material). Data are presented as mean ± SEM for n = 29 animals (pre-extinction: control, n = 8; MGv-lesion, n = 12; MGm-lesion, n = 9; post-extinction: control, n = 4; MGv-lesion, n = 7; MGm-lesion, n = 5). *p < 0.0167; ^‡p < 0.05.