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Impaired Processing in the Primary Auditory Cortex of an Animal Model of Autism.

Anomal RF, de Villers-Sidani E, Brandão JA, Diniz R, Costa MR, Romcy-Pereira RN - Front Syst Neurosci (2015)

Bottom Line: In this context, hearing incongruence is particularly prevalent.Considering that some of this abnormal processing might stem from the unbalance of inhibitory and excitatory drives in brain circuitries, we used an animal model of autism induced by valproic acid (VPA) during pregnancy in order to investigate the tonotopic organization of the primary auditory cortex (AI) and its local inhibitory circuitry.Altogether our findings show that neurophysiological impairments of hearing perception in this autism model occur independently of alterations in the number of parvalbumin-expressing interneurons.

View Article: PubMed Central - PubMed

Affiliation: Brain Institute, Federal University of Rio Grande do Norte Natal, Brazil.

ABSTRACT
Autism is a neurodevelopmental disorder clinically characterized by deficits in communication, lack of social interaction and repetitive behaviors with restricted interests. A number of studies have reported that sensory perception abnormalities are common in autistic individuals and might contribute to the complex behavioral symptoms of the disorder. In this context, hearing incongruence is particularly prevalent. Considering that some of this abnormal processing might stem from the unbalance of inhibitory and excitatory drives in brain circuitries, we used an animal model of autism induced by valproic acid (VPA) during pregnancy in order to investigate the tonotopic organization of the primary auditory cortex (AI) and its local inhibitory circuitry. Our results show that VPA rats have distorted primary auditory maps with over-representation of high frequencies, broadly tuned receptive fields and higher sound intensity thresholds as compared to controls. However, we did not detect differences in the number of parvalbumin-positive interneurons in AI of VPA and control rats. Altogether our findings show that neurophysiological impairments of hearing perception in this autism model occur independently of alterations in the number of parvalbumin-expressing interneurons. These data support the notion that fine circuit alterations, rather than gross cellular modification, could lead to neurophysiological changes in the autistic brain.

No MeSH data available.


Related in: MedlinePlus

Embryonic administration of VPA alters the maturation of receptive fields in AI. (A) Fraction of AI responsive sites at distinct sound frequency bands. VPA rats present larger cortical representation for sound frequencies above 10 kHz (F(3, 30) = 63.37, p < 0.05; two-way ANOVA with repeated measures, Bonferroni’s multiple comparison test). (B) Relative number of single and multi/flat-peaked receptive fields in each group. V-shaped receptive fields are significantly reduced in VPA animals as compared to controls, whereas multi-peaked sites are increased in this group (p < 0.01, Student’s t-test). (C) Sound intensity threshold of AI neurons in VPA rats is significantly higher than those measured in control animals (p < 0.01, Student’s t-test). (D) Frequency response bandwidth 10 dB above sound intensity threshold (BW10). Note that BW10 is significantly augmented in VPA rats (p < 0.0001, Student’s t-test). (E) Latency of neuronal responses in AI was significantly decreased in VPA rats as compared to controls (p < 0.01, Student’s t-test). Values are means ± SEM. *p < 0.05; **p < 0.01; ***p < 0.0001.
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Figure 3: Embryonic administration of VPA alters the maturation of receptive fields in AI. (A) Fraction of AI responsive sites at distinct sound frequency bands. VPA rats present larger cortical representation for sound frequencies above 10 kHz (F(3, 30) = 63.37, p < 0.05; two-way ANOVA with repeated measures, Bonferroni’s multiple comparison test). (B) Relative number of single and multi/flat-peaked receptive fields in each group. V-shaped receptive fields are significantly reduced in VPA animals as compared to controls, whereas multi-peaked sites are increased in this group (p < 0.01, Student’s t-test). (C) Sound intensity threshold of AI neurons in VPA rats is significantly higher than those measured in control animals (p < 0.01, Student’s t-test). (D) Frequency response bandwidth 10 dB above sound intensity threshold (BW10). Note that BW10 is significantly augmented in VPA rats (p < 0.0001, Student’s t-test). (E) Latency of neuronal responses in AI was significantly decreased in VPA rats as compared to controls (p < 0.01, Student’s t-test). Values are means ± SEM. *p < 0.05; **p < 0.01; ***p < 0.0001.

Mentions: Tuning curves were classified as v-shaped and multi-peaked according to previous studies in AI (Bao et al., 2004; Zhou and Merzenich, 2007; Anomal et al., 2013). The receptive field irregularity index was used to quantify eventual differences between control and experimental animals. The irregularity index was defined as [Corr(0, 0) − (Corr(1, 0) + Corr(0, 1))/2]/Corr(0, 0)1/2 minus a constant number of 3, where Corr(0, 0) represents the central term of the receptive field and Corr(0, 0) − (Corr(1, 0) + Corr(0, 1))/2 represents the periphery of the receptive field (Bao et al., 2003). After that, we calculated the percentage of sites presenting irregularity index above 2. Higher irregularity index means that the tuning curve is less v-shaped. Single-peaked sites were identified as a well-defined v-shaped tuning curve, containing one apex or one CF. Tuning curves without apex (flat design) or containing more than one apex were seen as flat/multi-peaked sites. For flat-peaked tuning curves, the median frequency at minimal intensity was chosen as the CF. For tuning curves presenting multiple-peaks, the CF was defined at the apex with lowest threshold. BW10 was defined as the range of frequencies in octaves (frequency response range) that was able to elicit neuronal responses 10 dB above intensity threshold. Characteristic frequencies, intensity thresholds and BW10 were computed using custom-made Matlab routines (MathWorks, Natick, MA, USA). Percentages of sites described in our results were obtained from the total number of recorded sites inside AI (see Figure 3). Response latency was defined as the time from stimulus onset to the multiunit response level 4 standard deviations above the mean pre-stimulus firing rate level.


Impaired Processing in the Primary Auditory Cortex of an Animal Model of Autism.

Anomal RF, de Villers-Sidani E, Brandão JA, Diniz R, Costa MR, Romcy-Pereira RN - Front Syst Neurosci (2015)

Embryonic administration of VPA alters the maturation of receptive fields in AI. (A) Fraction of AI responsive sites at distinct sound frequency bands. VPA rats present larger cortical representation for sound frequencies above 10 kHz (F(3, 30) = 63.37, p < 0.05; two-way ANOVA with repeated measures, Bonferroni’s multiple comparison test). (B) Relative number of single and multi/flat-peaked receptive fields in each group. V-shaped receptive fields are significantly reduced in VPA animals as compared to controls, whereas multi-peaked sites are increased in this group (p < 0.01, Student’s t-test). (C) Sound intensity threshold of AI neurons in VPA rats is significantly higher than those measured in control animals (p < 0.01, Student’s t-test). (D) Frequency response bandwidth 10 dB above sound intensity threshold (BW10). Note that BW10 is significantly augmented in VPA rats (p < 0.0001, Student’s t-test). (E) Latency of neuronal responses in AI was significantly decreased in VPA rats as compared to controls (p < 0.01, Student’s t-test). Values are means ± SEM. *p < 0.05; **p < 0.01; ***p < 0.0001.
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Figure 3: Embryonic administration of VPA alters the maturation of receptive fields in AI. (A) Fraction of AI responsive sites at distinct sound frequency bands. VPA rats present larger cortical representation for sound frequencies above 10 kHz (F(3, 30) = 63.37, p < 0.05; two-way ANOVA with repeated measures, Bonferroni’s multiple comparison test). (B) Relative number of single and multi/flat-peaked receptive fields in each group. V-shaped receptive fields are significantly reduced in VPA animals as compared to controls, whereas multi-peaked sites are increased in this group (p < 0.01, Student’s t-test). (C) Sound intensity threshold of AI neurons in VPA rats is significantly higher than those measured in control animals (p < 0.01, Student’s t-test). (D) Frequency response bandwidth 10 dB above sound intensity threshold (BW10). Note that BW10 is significantly augmented in VPA rats (p < 0.0001, Student’s t-test). (E) Latency of neuronal responses in AI was significantly decreased in VPA rats as compared to controls (p < 0.01, Student’s t-test). Values are means ± SEM. *p < 0.05; **p < 0.01; ***p < 0.0001.
Mentions: Tuning curves were classified as v-shaped and multi-peaked according to previous studies in AI (Bao et al., 2004; Zhou and Merzenich, 2007; Anomal et al., 2013). The receptive field irregularity index was used to quantify eventual differences between control and experimental animals. The irregularity index was defined as [Corr(0, 0) − (Corr(1, 0) + Corr(0, 1))/2]/Corr(0, 0)1/2 minus a constant number of 3, where Corr(0, 0) represents the central term of the receptive field and Corr(0, 0) − (Corr(1, 0) + Corr(0, 1))/2 represents the periphery of the receptive field (Bao et al., 2003). After that, we calculated the percentage of sites presenting irregularity index above 2. Higher irregularity index means that the tuning curve is less v-shaped. Single-peaked sites were identified as a well-defined v-shaped tuning curve, containing one apex or one CF. Tuning curves without apex (flat design) or containing more than one apex were seen as flat/multi-peaked sites. For flat-peaked tuning curves, the median frequency at minimal intensity was chosen as the CF. For tuning curves presenting multiple-peaks, the CF was defined at the apex with lowest threshold. BW10 was defined as the range of frequencies in octaves (frequency response range) that was able to elicit neuronal responses 10 dB above intensity threshold. Characteristic frequencies, intensity thresholds and BW10 were computed using custom-made Matlab routines (MathWorks, Natick, MA, USA). Percentages of sites described in our results were obtained from the total number of recorded sites inside AI (see Figure 3). Response latency was defined as the time from stimulus onset to the multiunit response level 4 standard deviations above the mean pre-stimulus firing rate level.

Bottom Line: In this context, hearing incongruence is particularly prevalent.Considering that some of this abnormal processing might stem from the unbalance of inhibitory and excitatory drives in brain circuitries, we used an animal model of autism induced by valproic acid (VPA) during pregnancy in order to investigate the tonotopic organization of the primary auditory cortex (AI) and its local inhibitory circuitry.Altogether our findings show that neurophysiological impairments of hearing perception in this autism model occur independently of alterations in the number of parvalbumin-expressing interneurons.

View Article: PubMed Central - PubMed

Affiliation: Brain Institute, Federal University of Rio Grande do Norte Natal, Brazil.

ABSTRACT
Autism is a neurodevelopmental disorder clinically characterized by deficits in communication, lack of social interaction and repetitive behaviors with restricted interests. A number of studies have reported that sensory perception abnormalities are common in autistic individuals and might contribute to the complex behavioral symptoms of the disorder. In this context, hearing incongruence is particularly prevalent. Considering that some of this abnormal processing might stem from the unbalance of inhibitory and excitatory drives in brain circuitries, we used an animal model of autism induced by valproic acid (VPA) during pregnancy in order to investigate the tonotopic organization of the primary auditory cortex (AI) and its local inhibitory circuitry. Our results show that VPA rats have distorted primary auditory maps with over-representation of high frequencies, broadly tuned receptive fields and higher sound intensity thresholds as compared to controls. However, we did not detect differences in the number of parvalbumin-positive interneurons in AI of VPA and control rats. Altogether our findings show that neurophysiological impairments of hearing perception in this autism model occur independently of alterations in the number of parvalbumin-expressing interneurons. These data support the notion that fine circuit alterations, rather than gross cellular modification, could lead to neurophysiological changes in the autistic brain.

No MeSH data available.


Related in: MedlinePlus