Associative responses to visual shape stimuli in the mouse auditory cortex

Abstract

Humans can recall various aspects of a characteristic sound as a whole when they see a visual shape stimulus that has been intimately associated with the sound. In subjects with audio-visual associative memory, auditory responses that code the associated sound may be induced in the auditory cortex in response to presentation of the associated visual shape stimulus. To test this possibility, mice were pre-exposed to a combination of an artificial sound mimicking a cat's "meow" and a visual shape stimulus of concentric circles or stars for more than two weeks, since such passive exposure is known to be sufficient for inducing audio-visual associative memory in mice. After the exposure, we anesthetized the mice, and presented them with the associated visual shape stimulus. We found that associative responses in the auditory cortex were induced in response to the visual stimulus. The associative auditory responses were observed when complex sounds such as "meow" were used for formation of audio-visual associative memory, but not when a pure tone was used. These results suggest that associative auditory responses in the auditory cortex represent the characteristics of the complex sound stimulus as a whole.

Fig 1. Methods for visualizing associative auditory responses.

(A) Spectrogram of an artificial sound mimicking the sound of a cat’s “meow”. A part of this sound lasting 1 s (horizontal line) was used in the present study. (B) Visual shape stimuli of concentric circles with an angle of view of approximately 20°, or stars. These images were used as test or control shape stimuli. (C) Experimental schedule. Mice were pre-exposed to the test visual shape stimulus synchronized with the “meow” sound, producing an audio-visual associative memory. After the exposure, mice were anesthetized and responses to the test visual stimulus and the other control shape stimulus were recorded in the AC. The difference between the responses was obtained in each mouse and averaged in a group of mice that received the same experimental procedure (n = 12–18 for each group).

Fig 2. Responses to auditory or visual shape stimuli in the AC.

(A) Image of responses to a pure tone at 5 kHz in the right AC (R5kHz). A1, AAF, and A2 were functionally identified. Circle shows patchy responses in AAF. Upper right corner in the panel corresponds to medial and anterior areas of the cortex. The pseudocolor scale shows ΔF/F₀. (B) Responses to a cat’s “meow” sound (R“meow”). The circular ROI shows the location of the characteristic patchy response in AAF. Data shown in (A) and (B) were obtained from the same mouse, and recorded 0.5 and 1 s after stimulus onset, respectively. (C) Responses to concentric circles (test shape stimulus) (R). Diffuse increases in ΔF/F₀ were observed in the AC. (D) Responses to stars (control shape stimulus) (R✶). Diffuse decreases in ΔF/F₀ were observed in the AC. Data shown in (C) and (D) were obtained from the same mouse, and recorded 1.8 s after stimulus onset. (E) Time courses of ΔF/F₀ within the circular ROI centered on AAF in 13 mice. Dots with lines show means and SEMs. Vertical scale bar: 0.3% for ΔF/F₀ in response to the “meow” sound, 0.1% in response to visual shape stimuli. Shaded square shows the timing of stimulus presentation.

Fig 3. Averaged responses to auditory or visual shape stimuli in the AC.

(A) Averaged responses in the AC to the “meow” stimulus in 13 mice pre-exposed to a combination of the “meow” sound and concentric circles (R“meow”). Arrow shows the position of AAF. The pseudocolor scale shows ΔF/F₀. (B) Associative auditory responses calculated as the differential responses to concentric circles (test) and stars (control) in the same 13 mice shown in (A) (R—R✶). Note the responses with positive amplitudes. (C) Averaged responses in the AC to the “meow” stimulus in 14 mice pre-exposed to a combination of the “meow” sound and stars (R“meow”). (D) Associative auditory responses calculated as the differential responses to concentric circles (control) and stars (test) in the same 14 mice shown in (C) (R—R✶). Note the responses with negative amplitudes. Data shown in (A) and (C) were recorded 1 s after stimulus onset, and those in (B) and (D) were recorded 1.8 s after stimulus onset. (E) Time courses of ΔF/F₀ within the circular ROI centered on AAF in (B) and (D). Dots with lines show means and SEMs.

Fig 4. Associative auditory responses in the AC to visual stimuli.

Amplitudes of the associative responses to a 5 kHz pure tone, FM tone, harmonic tone, FM harmonic tone, and a “meow” sound (red columns). Columns with lines show means and SEMs. Concentric circles and stars were used as visual shape stimuli. Amplitudes of control responses with no pre-exposure are shown by a blue column.