Fig. 4: Auditory threat conditioning is modulated by auditory association cortex neurons projecting to SNL. | Nature Communications

Fig. 4: Auditory threat conditioning is modulated by auditory association cortex neurons projecting to SNL.

From: Corticonigral projections recruit substantia nigra pars lateralis dopaminergic neurons for auditory threat memories

Fig. 4

a Illustration showing infection strategy with 2 viral injections: Retrograde AAV9-Cre in SNL, followed by AAV-DIO-eGFP or AAV-DIO-eGFP-TetTx in AuV/TeA. b Representative brightfield and fluorescence images showing the extent of viral infection in AuV/TeA/SNL. c Behavioral paradigm used for FM auditory threat conditioning. d–f Graphs showing average % freeze for habituation, conditioning, and retrieval phases. Squared symbols represent average % freeze during FM tone trains (control, N = 8; TetTx, N = 6). Whisker bars are ± SEM. g Average % freeze during FM tones for control (eGFP, N = 8, gray) and treated (TetTx, N = 6, red) mice. Square symbols represent averages from a single mouse. Two-way ANOVA showed significant treatment (p = 0.012), but not phase (p = 0.60), or phase-treatment interaction (p = 0.36). Sidak’s post-hoc test revealed a significant difference between groups during retrieval (p = 0.02). h Behavioral paradigm used for simple tones auditory threat conditioning. i–k Graph showing average % freeze for habituation/conditioning, retrieval, and contextual phases. Squared symbols represent the freeze average during a single pure tone for habituation/conditioning and retrieval (control, N = 8; TetTx, N = 8). Whisker bars are ± SEM. l Average % freeze during simple tones for control (eGFP, N = 8, gray) and treated (TetTx, N = 8, red) mice. Every squared symbol represents the average from a single mouse. Two-way ANOVA showed significant treatment (p = 0.0398), but not phase (p = 0.51), or phase-treatment interaction (p = 0.98). Average % freeze resulted significantly different between control and treated mice for Contextual Freezing (p = 0.048, Mann-Whitney). Box whiskers represent 25–75% percentiles, solid squares are mean value, horizontal box lines represent medians. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. C57BL/6 J mice were used at 3 months of age, and each experimental group was composed of 50% male and 50% male. Created in BioRender. Sansalone, L. (2025) https://BioRender.com/3uulg98. Source data have been uploaded on Zenodo (https://doi.org/10.5281/zenodo.15486331, 2025).

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