RESUMEN
In our previous study, we showed that the defense responses induced by the selective optogenetic activation of the uncrossed output pathway from the deeper layer of the superior colliculus were environment dependent in the mouse. In a small closed box, the stimulus frequently induced flight (fast forward run away) responses, while in a large open field, the stimulus tended to induce backward retreat responses. We tested a hypothesis that the amygdala is involved in such environment dependency of the innate defense responses. For this purpose, we made a bilateral lesion of the amygdala induced by the ibotenic acid injections in male mice. As a result, in the mice with lesions of substantial portions of the basolateral and basomedial complex, the flight responses in the closed box disappeared and retreat responses were mainly induced. The retreat responses on the open platform were unchanged. Classically, the amygdala has been considered to be involved in the memory-dependent contextual modulation of the fear responses. In contrast, the present results suggest a novel view on the role of the amygdala in which the amygdala plays a key role in sensing the current environmental setting for making a quick decision of action upon emergency, which is critical for survival in the natural environment.
Asunto(s)
Miedo , Colículos Superiores , Amígdala del Cerebelo , Animales , Masculino , Ratones , OptogenéticaRESUMEN
Superior colliculus (SC) is a midbrain structure that integrates sensory inputs and generates motor commands to initiate innate motor behaviors. Its retinorecipient superficial layers (sSC) receive dense cholinergic projections from the parabigeminal nucleus (PBN). Our previous in vitro study revealed that acetylcholine induces fast inward current followed by prominent GABAergic inhibition within the sSC circuits (Endo T, Yanagawa Y, Obata K, Isa T. J Neurophysiol 94: 3893-3902, 2005). Acetylcholine-mediated facilitation of GABAergic inhibition may play an important role in visual signal processing in the sSC; however, both the anatomical and physiological properties of cholinergic inputs from PBN have not been studied in detail in vivo. In this study, we specifically visualized and optogenetically manipulated the cholinergic neurons in the PBN after focal injections of Cre-dependent viral vectors in mice that express Cre in cholinergic neurons. We revealed that the cholinergic projections terminated densely in the medial part of the mouse sSC. This suggests that the cholinergic inputs mediate visual processing in the upper visual field, which would be critical for predator detection. We further analyzed the physiological roles of the cholinergic inputs by recording looming-evoked visual responses from sSC neurons during optogenetic activation or inactivation of PBN cholinergic neurons in anesthetized mice. We found that optogenetic manipulations in either direction induced response suppression in most neurons, whereas response facilitation was observed in a few neurons after the optogenetic activation. These results support a circuit model that suggests that the PBN cholinergic inputs enhance functions of the sSC in detecting visual targets by facilitating the center excitation-surround inhibition.NEW & NOTEWORTHY The modulatory role of the cholinergic inputs from the parabigeminal nucleus in the visual responses in the superficial superior colliculus (sSC) remains unknown. Here we report that the cholinergic projections terminate densely in the medial sSC and optogenetic manipulations of the cholinergic inputs affect the looming-evoked response and enhance surround inhibition in the sSC. Our data suggest that cholinergic inputs to the sSC contribute to the visual detection of predators.
Asunto(s)
Neuronas Colinérgicas/fisiología , Potenciales Evocados Visuales/fisiología , Techo del Mesencéfalo/fisiología , Campos Visuales/fisiología , Vías Visuales/fisiología , Animales , Masculino , Ratones , Ratones Transgénicos , Optogenética , Colículos Superiores/fisiologíaRESUMEN
Mutations in the gene encoding the chromatin remodeler CHD8 are strongly associated with autism spectrum disorder (ASD). CHD8 haploinsufficiency also results in autistic phenotypes in humans and mice. Although myelination defects have been observed in individuals with ASD, whether oligodendrocyte dysfunction is responsible for autistic phenotypes has remained unknown. Here we show that reduced expression of CHD8 in oligodendrocytes gives rise to abnormal behavioral phenotypes in mice. CHD8 was found to regulate the expression of many myelination-related genes and to be required for oligodendrocyte maturation and myelination. Ablation of Chd8 specifically in oligodendrocytes of mice impaired myelination, slowed action potential propagation and resulted in behavioral deficits including increased social interaction and anxiety-like behavior, with similar effects being apparent in Chd8 heterozygous mutant mice. Our results thus indicate that CHD8 is essential for myelination and that dysfunction of oligodendrocytes as a result of CHD8 haploinsufficiency gives rise to several neuropsychiatric phenotypes.