Cacciato-Salcedo Sara, Lao-Rodríguez Ana B, Malmierca Manuel S
Cognitive and Auditory Neuroscience Laboratory (CANELAB), Institute of Neuroscience of Castilla y León (INCYL), Salamanca, Spain.
Salamanca Institute for Biomedical Research (IBSAL), Salamanca, Spain.
PLoS Biol. 2025 Aug 4;23(8):e3003309. doi: 10.1371/journal.pbio.3003309. eCollection 2025 Aug.
Diverse biological factors, such as sex and age, confer heterogeneity on sensory processing challenges in autism. These factors result in major difficulties in the processing of contextual information in social and non-social situations. To assess divergence in autistic traits, it is critical to consider sex- and age-related variability. Nevertheless, these differences remain largely elusive. Animal models of autism offer the possibility to examine contextual processing at the single-neuron level. Here, we investigated predictive processing of contextual auditory cues in the auditory midbrain of control and prenatally valproic acid-induced rats, a well-established animal model of autism. The rats were prepubertal and adult female and male animals. We performed single-unit recordings in the inferior colliculus of control and prenatally, or in utero, exposed rats under the classical oddball paradigm and non-repetitive cascade control sequences to study neuronal mismatch. This is the neuronal correlate of mismatch negativity, the brain's automatic response to interruptions in environmental regularity. When comparing control and exposed rats, our results demonstrated a reduction in neuronal mismatch in rats exposed to valproic acid. However, exposed adult females exhibited an increased neuronal mismatch compared to their control counterparts. With respect to sex distinctions, valproic acid induced sex differences in neuronal mismatch of prepubertal and adult rats that are not observable in control animals. Moreover, we detected an age-dependent refinement in prediction error that is not affected by the drug. But valproic acid altered typical developmental trajectory of neuronal mismatch in both sexes. Such observations support sex- and age-related effects of in utero valproic acid exposure in contextual auditory processing at the neural level of the inferior colliculus. In autism, atypical predictive processing of environmental regularities underlies unusual responses to novel experiences. The present study highlights the importance of sex and age, that confer heterogeneity to these challenges.
多种生物学因素，如性别和年龄，使得自闭症患者在感觉处理方面面临的挑战具有异质性。这些因素导致在社交和非社交情境中处理情境信息时出现重大困难。为了评估自闭症特征的差异，考虑与性别和年龄相关的变异性至关重要。然而，这些差异在很大程度上仍然难以捉摸。自闭症动物模型为在单神经元水平研究情境处理提供了可能性。在此，我们研究了对照大鼠和产前丙戊酸诱导的大鼠（一种成熟的自闭症动物模型）听觉中脑中情境听觉线索的预测处理。这些大鼠为青春期前和成年的雌性及雄性动物。我们在经典的oddball范式和非重复级联控制序列下，对对照大鼠以及产前或子宫内暴露的大鼠的下丘进行单单位记录，以研究神经元失配。这是失配负波的神经元相关物，即大脑对环境规律性中断的自动反应。当比较对照大鼠和暴露大鼠时，我们的结果表明丙戊酸暴露大鼠的神经元失配减少。然而，暴露的成年雌性大鼠与其对照 counterparts相比，神经元失配增加。关于性别差异，丙戊酸在青春期前和成年大鼠的神经元失配中诱导了性别差异，而在对照动物中未观察到这种差异。此外，我们检测到预测误差存在年龄依赖性的细化，且不受药物影响。但丙戊酸改变了两性神经元失配的典型发育轨迹。这些观察结果支持子宫内丙戊酸暴露在神经水平的下丘情境听觉处理中与性别和年龄相关的影响。在自闭症中，对环境规律性的非典型预测处理是对新体验异常反应的基础。本研究强调了性别和年龄的重要性，它们赋予了这些挑战以异质性。
