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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

Electrophysiological mapping of the primary auditory cortex. (A) Anatomical disposition of the rat’s temporal cortex at left hemisphere. (B) Primary auditory cortex is dorsal to rhinal fissure and caudal to middle cerebral artery, where the center of an 8 × 8 microelectrode array (375 × 500 mm grid) was placed for the electrophysiological recordings. (C)Left, Illustrative neuronal responses in AI to pure tone pulse stimuli. Here, we show one recording site of a control and a valproic acid (VPA) animal. Right, Normalized activation plots corresponding to AI on the left. Each value in the map represents the average of three trials for each bin (1 ms). Colors represent interpolated and normalized firing rate counts. Calibration bar = 1 mm.
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Figure 1: Electrophysiological mapping of the primary auditory cortex. (A) Anatomical disposition of the rat’s temporal cortex at left hemisphere. (B) Primary auditory cortex is dorsal to rhinal fissure and caudal to middle cerebral artery, where the center of an 8 × 8 microelectrode array (375 × 500 mm grid) was placed for the electrophysiological recordings. (C)Left, Illustrative neuronal responses in AI to pure tone pulse stimuli. Here, we show one recording site of a control and a valproic acid (VPA) animal. Right, Normalized activation plots corresponding to AI on the left. Each value in the map represents the average of three trials for each bin (1 ms). Colors represent interpolated and normalized firing rate counts. Calibration bar = 1 mm.

Mentions: The left primary auditory cortex of rats was mapped as previously described (de Villers-Sidani et al., 2007; Anomal et al., 2013). Rats assigned to control and VPA group were obtained in equal number from two pregnant females. Briefly, they were anesthetized with a cocktail of ketamine (50 mg/kg, i.p.), xylazine (5 mg/kg, i.p.), acepromazine (1 mg/kg, i.p.), and received an injection of the anti-inflammatory dexamethasone (0.2 mg/kg, i.p.) before surgery. Body temperature was maintained with a heating pad at 36 ± 1°C. The cistern magna was drained of cerebrospinal fluid to minimize cerebral edema. The skull was kept fixed by a head holder, leaving the ears unobstructed. The left or right temporalis muscle was reflected exposing the auditory cortex and the dura-mater was resected to broadly uncover AI. AI was anatomically identified as outlined by the medial cerebral artery, dorsal to the rhinal fissure (Figures 1A,B; see also Krubitzer et al., 2011).


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)

Electrophysiological mapping of the primary auditory cortex. (A) Anatomical disposition of the rat’s temporal cortex at left hemisphere. (B) Primary auditory cortex is dorsal to rhinal fissure and caudal to middle cerebral artery, where the center of an 8 × 8 microelectrode array (375 × 500 mm grid) was placed for the electrophysiological recordings. (C)Left, Illustrative neuronal responses in AI to pure tone pulse stimuli. Here, we show one recording site of a control and a valproic acid (VPA) animal. Right, Normalized activation plots corresponding to AI on the left. Each value in the map represents the average of three trials for each bin (1 ms). Colors represent interpolated and normalized firing rate counts. Calibration bar = 1 mm.
© Copyright Policy
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4644803&req=5

Figure 1: Electrophysiological mapping of the primary auditory cortex. (A) Anatomical disposition of the rat’s temporal cortex at left hemisphere. (B) Primary auditory cortex is dorsal to rhinal fissure and caudal to middle cerebral artery, where the center of an 8 × 8 microelectrode array (375 × 500 mm grid) was placed for the electrophysiological recordings. (C)Left, Illustrative neuronal responses in AI to pure tone pulse stimuli. Here, we show one recording site of a control and a valproic acid (VPA) animal. Right, Normalized activation plots corresponding to AI on the left. Each value in the map represents the average of three trials for each bin (1 ms). Colors represent interpolated and normalized firing rate counts. Calibration bar = 1 mm.
Mentions: The left primary auditory cortex of rats was mapped as previously described (de Villers-Sidani et al., 2007; Anomal et al., 2013). Rats assigned to control and VPA group were obtained in equal number from two pregnant females. Briefly, they were anesthetized with a cocktail of ketamine (50 mg/kg, i.p.), xylazine (5 mg/kg, i.p.), acepromazine (1 mg/kg, i.p.), and received an injection of the anti-inflammatory dexamethasone (0.2 mg/kg, i.p.) before surgery. Body temperature was maintained with a heating pad at 36 ± 1°C. The cistern magna was drained of cerebrospinal fluid to minimize cerebral edema. The skull was kept fixed by a head holder, leaving the ears unobstructed. The left or right temporalis muscle was reflected exposing the auditory cortex and the dura-mater was resected to broadly uncover AI. AI was anatomically identified as outlined by the medial cerebral artery, dorsal to the rhinal fissure (Figures 1A,B; see also Krubitzer et al., 2011).

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