Pub Date : 2023-01-18DOI: 10.1101/2023.01.18.524515
Francesca Binda, Ludovic Spaeth, Arvind Kumar, P. Isope
The cerebellar cortex computes sensorimotor information from many brain areas through a feedforward inhibitory (FFI) microcircuit between the input stage, the granule cell (GC) layer, and the output stage, the Purkinje cells (PCs). Although in other brain areas FFI underlies a precise excitation versus inhibition temporal correlation, recent findings in the cerebellum highlighted more complex behaviors at GC–molecular layer interneuron (MLI)–PC pathway. To dissect the temporal organization of this cerebellar FFI pathway, we combined ex vivo patch-clamp recordings of PCs in male mice with a viral-based strategy to express Channelrhodopsin2 in a subset of mossy fibers (MFs), the major excitatory inputs to GCs. We show that although light-mediated MF activation elicited pairs of excitatory and inhibitory postsynaptic currents in PCs, excitation (E) from GCs and inhibition (I) from MLIs reached PCs with a wide range of different temporal delays. However, when GCs were directly stimulated, a low variability in E/I delays was observed. Our results demonstrate that in many recordings MF stimulation recruited different groups of GCs that trigger E and/or I, and expanded PC temporal synaptic integration. Finally, using a computational model of the FFI pathway, we showed that this temporal expansion could strongly influence how PCs integrate GC inputs. Our findings show that specific E/I delays may help PCs encoding specific MF inputs. SIGNIFICANCE STATEMENT Sensorimotor information is conveyed to the cerebellar cortex by mossy fibers. Mossy fiber inputs activate granule cells that excite molecular interneurons and Purkinje cells, the sole output of the cerebellar cortex, leading to a sequence of synaptic excitation and inhibition in Purkinje cells, thus defining a feedforward inhibitory pathway. Using electrophysiological recordings, optogenetic stimulation, and mathematical modeling, we demonstrated that different groups of granule cells can elicit synaptic excitation and inhibition with various latencies onto Purkinje cells. This temporal variability controls how granule cells influence Purkinje cell discharge and may support temporal coding in the cerebellar cortex.
{"title":"Excitation and Inhibition Delays within a Feedforward Inhibitory Pathway Modulate Cerebellar Purkinje Cell Output in Mice","authors":"Francesca Binda, Ludovic Spaeth, Arvind Kumar, P. Isope","doi":"10.1101/2023.01.18.524515","DOIUrl":"https://doi.org/10.1101/2023.01.18.524515","url":null,"abstract":"The cerebellar cortex computes sensorimotor information from many brain areas through a feedforward inhibitory (FFI) microcircuit between the input stage, the granule cell (GC) layer, and the output stage, the Purkinje cells (PCs). Although in other brain areas FFI underlies a precise excitation versus inhibition temporal correlation, recent findings in the cerebellum highlighted more complex behaviors at GC–molecular layer interneuron (MLI)–PC pathway. To dissect the temporal organization of this cerebellar FFI pathway, we combined ex vivo patch-clamp recordings of PCs in male mice with a viral-based strategy to express Channelrhodopsin2 in a subset of mossy fibers (MFs), the major excitatory inputs to GCs. We show that although light-mediated MF activation elicited pairs of excitatory and inhibitory postsynaptic currents in PCs, excitation (E) from GCs and inhibition (I) from MLIs reached PCs with a wide range of different temporal delays. However, when GCs were directly stimulated, a low variability in E/I delays was observed. Our results demonstrate that in many recordings MF stimulation recruited different groups of GCs that trigger E and/or I, and expanded PC temporal synaptic integration. Finally, using a computational model of the FFI pathway, we showed that this temporal expansion could strongly influence how PCs integrate GC inputs. Our findings show that specific E/I delays may help PCs encoding specific MF inputs. SIGNIFICANCE STATEMENT Sensorimotor information is conveyed to the cerebellar cortex by mossy fibers. Mossy fiber inputs activate granule cells that excite molecular interneurons and Purkinje cells, the sole output of the cerebellar cortex, leading to a sequence of synaptic excitation and inhibition in Purkinje cells, thus defining a feedforward inhibitory pathway. Using electrophysiological recordings, optogenetic stimulation, and mathematical modeling, we demonstrated that different groups of granule cells can elicit synaptic excitation and inhibition with various latencies onto Purkinje cells. This temporal variability controls how granule cells influence Purkinje cell discharge and may support temporal coding in the cerebellar cortex.","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"1 1","pages":"5905 - 5917"},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86541628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-18DOI: 10.1523/JNEUROSCI.twij.43.3.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/JNEUROSCI.twij.43.3.2023","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.twij.43.3.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"19 1","pages":"346 - 346"},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73054438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-11DOI: 10.1523/JNEUROSCI.twij.43.2.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/JNEUROSCI.twij.43.2.2023","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.twij.43.2.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"20 1","pages":"183 - 183"},"PeriodicalIF":0.0,"publicationDate":"2023-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72979047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-11DOI: 10.1101/2022.03.04.482801
Yi-Seon Jeon, Daun Jeong, Hanseul Kweon, Jae-Hyun Kim, Choong Yeon Kim, Youngbin Oh, Young-Ho Lee, C. Kim, Sang-Gyu Kim, Jae-Woong Jeong, Eunjoon Kim, Seung-Hee Lee
The adolescent social experience is essential for the maturation of the prefrontal cortex in mammalian species. However, it still needs to be determined which cortical circuits mature with such experience and how it shapes adult social behaviors in a sex-specific manner. Here, we examined social-approaching behaviors in male and female mice after postweaning social isolation (PWSI), which deprives social experience during adolescence. We found that the PWSI, particularly isolation during late adolescence, caused an abnormal increase in social approaches (hypersociability) only in female mice. We further found that the PWSI female mice showed reduced parvalbumin (PV) expression in the left orbitofrontal cortex (OFCL). When we measured neural activity in the female OFCL, a substantial number of neurons showed higher activity when mice sniffed other mice (social sniffing) than when they sniffed an object (object sniffing). Interestingly, the PWSI significantly reduced both the number of activated neurons and the activity level during social sniffing in female mice. Similarly, the CRISPR/Cas9-mediated knockdown of PV in the OFCL during late adolescence enhanced sociability and reduced the social sniffing-induced activity in adult female mice via decreased excitability of PV+ neurons and reduced synaptic inhibition in the OFCL. Moreover, optogenetic activation of excitatory neurons or optogenetic inhibition of PV+ neurons in the OFCL enhanced sociability in female mice. Our data demonstrate that the adolescent social experience is critical for the maturation of PV+ inhibitory circuits in the OFCL; this maturation shapes female social behavior via enhancing social representation in the OFCL. SIGNIFICANCE STATEMENT Adolescent social isolation often changes adult social behaviors in mammals. Yet, we do not fully understand the sex-specific effects of social isolation and the brain areas and circuits that mediate such changes. Here, we found that adolescent social isolation causes three abnormal phenotypes in female but not male mice: hypersociability, decreased PV+ neurons in the left orbitofrontal cortex (OFCL), and decreased socially evoked activity in the OFCL. Moreover, parvalbumin (PV) deletion in the OFCL in vivo caused the same phenotypes in female mice by increasing excitation compared with inhibition within the OFCL. Our data suggest that adolescent social experience is required for PV maturation in the OFCL, which is critical for evoking OFCL activity that shapes social behaviors in female mice.
{"title":"Adolescent Parvalbumin Expression in the Left Orbitofrontal Cortex Shapes Sociability in Female Mice","authors":"Yi-Seon Jeon, Daun Jeong, Hanseul Kweon, Jae-Hyun Kim, Choong Yeon Kim, Youngbin Oh, Young-Ho Lee, C. Kim, Sang-Gyu Kim, Jae-Woong Jeong, Eunjoon Kim, Seung-Hee Lee","doi":"10.1101/2022.03.04.482801","DOIUrl":"https://doi.org/10.1101/2022.03.04.482801","url":null,"abstract":"The adolescent social experience is essential for the maturation of the prefrontal cortex in mammalian species. However, it still needs to be determined which cortical circuits mature with such experience and how it shapes adult social behaviors in a sex-specific manner. Here, we examined social-approaching behaviors in male and female mice after postweaning social isolation (PWSI), which deprives social experience during adolescence. We found that the PWSI, particularly isolation during late adolescence, caused an abnormal increase in social approaches (hypersociability) only in female mice. We further found that the PWSI female mice showed reduced parvalbumin (PV) expression in the left orbitofrontal cortex (OFCL). When we measured neural activity in the female OFCL, a substantial number of neurons showed higher activity when mice sniffed other mice (social sniffing) than when they sniffed an object (object sniffing). Interestingly, the PWSI significantly reduced both the number of activated neurons and the activity level during social sniffing in female mice. Similarly, the CRISPR/Cas9-mediated knockdown of PV in the OFCL during late adolescence enhanced sociability and reduced the social sniffing-induced activity in adult female mice via decreased excitability of PV+ neurons and reduced synaptic inhibition in the OFCL. Moreover, optogenetic activation of excitatory neurons or optogenetic inhibition of PV+ neurons in the OFCL enhanced sociability in female mice. Our data demonstrate that the adolescent social experience is critical for the maturation of PV+ inhibitory circuits in the OFCL; this maturation shapes female social behavior via enhancing social representation in the OFCL. SIGNIFICANCE STATEMENT Adolescent social isolation often changes adult social behaviors in mammals. Yet, we do not fully understand the sex-specific effects of social isolation and the brain areas and circuits that mediate such changes. Here, we found that adolescent social isolation causes three abnormal phenotypes in female but not male mice: hypersociability, decreased PV+ neurons in the left orbitofrontal cortex (OFCL), and decreased socially evoked activity in the OFCL. Moreover, parvalbumin (PV) deletion in the OFCL in vivo caused the same phenotypes in female mice by increasing excitation compared with inhibition within the OFCL. Our data suggest that adolescent social experience is required for PV maturation in the OFCL, which is critical for evoking OFCL activity that shapes social behaviors in female mice.","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"113 1","pages":"1555 - 1571"},"PeriodicalIF":0.0,"publicationDate":"2023-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76213185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-10DOI: 10.1101/2023.01.09.523360
A. Ingiosi, C. Hayworth, M. Frank
Mammalian sleep is regulated by a homeostatic process that increases sleep drive and intensity as a function of prior wake time. Sleep homeostasis has traditionally been thought to be a product of neurons, but recent findings demonstrate that this process is also modulated by glial astrocytes. The precise role of astrocytes in the accumulation and discharge of sleep drive is unknown. We investigated this question by selectively activating basal forebrain (BF) astrocytes using designer receptors exclusively activated by designer drugs (DREADDs) in male and female mice. DREADD activation of the Gq-protein-coupled pathway in BF astrocytes produced long and continuous periods of wakefulness that paradoxically did not cause the expected homeostatic response to sleep loss (e.g., increases in sleep time or intensity). Further investigations showed that this was not because of indirect effects of the ligand that activated DREADDs. These findings suggest that the need for sleep is not only driven by wakefulness per se, but also by specific neuronal-glial circuits that are differentially activated in wakefulness. SIGNIFICANCE STATEMENT Sleep drive is controlled by a homeostatic process that increases sleep duration and intensity based on prior time spent awake. Non-neuronal brain cells (e.g., glial astrocytes) influence this homeostatic process, but their precise role is unclear. We used a genetic technique to activate astrocytes in the basal forebrain (BF) of mice, a brain region important for sleep and wake expression and sleep homeostasis. Astroglial activation induced prolonged wakefulness without the expected homeostatic increase in sleep drive (i.e., sleep duration and intensity). These findings indicate that our need to sleep is also driven by non-neuronal cells, and not only by time spent awake.
{"title":"Activation of Basal Forebrain Astrocytes Induces Wakefulness without Compensatory Changes in Sleep Drive","authors":"A. Ingiosi, C. Hayworth, M. Frank","doi":"10.1101/2023.01.09.523360","DOIUrl":"https://doi.org/10.1101/2023.01.09.523360","url":null,"abstract":"Mammalian sleep is regulated by a homeostatic process that increases sleep drive and intensity as a function of prior wake time. Sleep homeostasis has traditionally been thought to be a product of neurons, but recent findings demonstrate that this process is also modulated by glial astrocytes. The precise role of astrocytes in the accumulation and discharge of sleep drive is unknown. We investigated this question by selectively activating basal forebrain (BF) astrocytes using designer receptors exclusively activated by designer drugs (DREADDs) in male and female mice. DREADD activation of the Gq-protein-coupled pathway in BF astrocytes produced long and continuous periods of wakefulness that paradoxically did not cause the expected homeostatic response to sleep loss (e.g., increases in sleep time or intensity). Further investigations showed that this was not because of indirect effects of the ligand that activated DREADDs. These findings suggest that the need for sleep is not only driven by wakefulness per se, but also by specific neuronal-glial circuits that are differentially activated in wakefulness. SIGNIFICANCE STATEMENT Sleep drive is controlled by a homeostatic process that increases sleep duration and intensity based on prior time spent awake. Non-neuronal brain cells (e.g., glial astrocytes) influence this homeostatic process, but their precise role is unclear. We used a genetic technique to activate astrocytes in the basal forebrain (BF) of mice, a brain region important for sleep and wake expression and sleep homeostasis. Astroglial activation induced prolonged wakefulness without the expected homeostatic increase in sleep drive (i.e., sleep duration and intensity). These findings indicate that our need to sleep is also driven by non-neuronal cells, and not only by time spent awake.","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"10 1","pages":"5792 - 5809"},"PeriodicalIF":0.0,"publicationDate":"2023-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83470914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-08DOI: 10.1101/2022.09.23.509292
Margaret M. Henderson, M. Tarr, Leila Wehbe
Midlevel features, such as contour and texture, provide a computational link between low- and high-level visual representations. Although the nature of midlevel representations in the brain is not fully understood, past work has suggested a texture statistics model, called the P–S model (Portilla and Simoncelli, 2000), is a candidate for predicting neural responses in areas V1–V4 as well as human behavioral data. However, it is not currently known how well this model accounts for the responses of higher visual cortex to natural scene images. To examine this, we constructed single-voxel encoding models based on P–S statistics and fit the models to fMRI data from human subjects (both sexes) from the Natural Scenes Dataset (Allen et al., 2022). We demonstrate that the texture statistics encoding model can predict the held-out responses of individual voxels in early retinotopic areas and higher-level category-selective areas. The ability of the model to reliably predict signal in higher visual cortex suggests that the representation of texture statistics features is widespread throughout the brain. Furthermore, using variance partitioning analyses, we identify which features are most uniquely predictive of brain responses and show that the contributions of higher-order texture features increase from early areas to higher areas on the ventral and lateral surfaces. We also demonstrate that patterns of sensitivity to texture statistics can be used to recover broad organizational axes within visual cortex, including dimensions that capture semantic image content. These results provide a key step forward in characterizing how midlevel feature representations emerge hierarchically across the visual system. SIGNIFICANCE STATEMENT Intermediate visual features, like texture, play an important role in cortical computations and may contribute to tasks like object and scene recognition. Here, we used a texture model proposed in past work to construct encoding models that predict the responses of neural populations in human visual cortex (measured with fMRI) to natural scene stimuli. We show that responses of neural populations at multiple levels of the visual system can be predicted by this model, and that the model is able to reveal an increase in the complexity of feature representations from early retinotopic cortex to higher areas of ventral and lateral visual cortex. These results support the idea that texture-like representations may play a broad underlying role in visual processing.
中级特征，如轮廓和纹理，提供了低级和高级视觉表示之间的计算链接。虽然大脑中中层表征的性质尚未完全被理解，但过去的工作已经提出了一种纹理统计模型，称为P-S模型(Portilla和Simoncelli, 2000)，是预测V1-V4区域神经反应以及人类行为数据的候选模型。然而，目前尚不清楚该模型如何很好地解释高级视觉皮层对自然场景图像的反应。为了验证这一点，我们基于P-S统计构建了单体素编码模型，并将模型拟合到来自自然场景数据集(Allen et al.， 2022)的人类受试者(男女)的fMRI数据中。我们证明了纹理统计编码模型可以预测单个体素在早期视网膜病变区域和更高级别类别选择区域的hold - down响应。该模型可靠地预测高级视觉皮层信号的能力表明，纹理统计特征的表征在整个大脑中广泛存在。此外，使用方差划分分析，我们确定了哪些特征是最独特的预测大脑反应，并表明高阶纹理特征的贡献从早期区域增加到腹侧表面的高级区域。我们还证明，纹理统计的敏感性模式可用于恢复视觉皮层内的广泛组织轴，包括捕获语义图像内容的维度。这些结果为描述中级特征表征如何在视觉系统中分层出现提供了关键的一步。中间视觉特征，如纹理，在皮质计算中起着重要作用，可能有助于物体和场景识别等任务。在这里，我们使用过去工作中提出的纹理模型来构建编码模型，预测人类视觉皮层神经群对自然场景刺激的反应(用fMRI测量)。我们发现，该模型可以预测视觉系统多个层次的神经群体的反应，并且该模型能够揭示从早期视网膜异位皮层到腹侧和外侧视觉皮层更高区域的特征表征复杂性的增加。这些结果支持了纹理表征可能在视觉处理中发挥广泛潜在作用的观点。
{"title":"A Texture Statistics Encoding Model Reveals Hierarchical Feature Selectivity across Human Visual Cortex","authors":"Margaret M. Henderson, M. Tarr, Leila Wehbe","doi":"10.1101/2022.09.23.509292","DOIUrl":"https://doi.org/10.1101/2022.09.23.509292","url":null,"abstract":"Midlevel features, such as contour and texture, provide a computational link between low- and high-level visual representations. Although the nature of midlevel representations in the brain is not fully understood, past work has suggested a texture statistics model, called the P–S model (Portilla and Simoncelli, 2000), is a candidate for predicting neural responses in areas V1–V4 as well as human behavioral data. However, it is not currently known how well this model accounts for the responses of higher visual cortex to natural scene images. To examine this, we constructed single-voxel encoding models based on P–S statistics and fit the models to fMRI data from human subjects (both sexes) from the Natural Scenes Dataset (Allen et al., 2022). We demonstrate that the texture statistics encoding model can predict the held-out responses of individual voxels in early retinotopic areas and higher-level category-selective areas. The ability of the model to reliably predict signal in higher visual cortex suggests that the representation of texture statistics features is widespread throughout the brain. Furthermore, using variance partitioning analyses, we identify which features are most uniquely predictive of brain responses and show that the contributions of higher-order texture features increase from early areas to higher areas on the ventral and lateral surfaces. We also demonstrate that patterns of sensitivity to texture statistics can be used to recover broad organizational axes within visual cortex, including dimensions that capture semantic image content. These results provide a key step forward in characterizing how midlevel feature representations emerge hierarchically across the visual system. SIGNIFICANCE STATEMENT Intermediate visual features, like texture, play an important role in cortical computations and may contribute to tasks like object and scene recognition. Here, we used a texture model proposed in past work to construct encoding models that predict the responses of neural populations in human visual cortex (measured with fMRI) to natural scene stimuli. We show that responses of neural populations at multiple levels of the visual system can be predicted by this model, and that the model is able to reveal an increase in the complexity of feature representations from early retinotopic cortex to higher areas of ventral and lateral visual cortex. These results support the idea that texture-like representations may play a broad underlying role in visual processing.","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"48 1","pages":"4144 - 4161"},"PeriodicalIF":0.0,"publicationDate":"2023-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74934026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-22DOI: 10.1101/2022.12.22.521614
A. Fjell, Øystein Sørensen, Yunpeng Wang, I. Amlien, W. Baaré, D. Bartrés-Faz, C. Boraxbekk, A. Brandmaier, I. Demuth, C. Drevon, Klaus P. Ebmeier, P. Ghisletta, R. Kievit, S. Kühn, K. S. Madsen, L. Nyberg, C. Solé-Padullés, D. Vidal-Piñeiro, G. Wagner, L. O. Watne, K. Walhovd
Many sleep less than recommended without experiencing daytime sleepiness. According to prevailing views, short sleep increases risk of lower brain health and cognitive function. Chronic mild sleep deprivation could cause undetected sleep debt, negatively affecting cognitive function and brain health. However, it is possible that some have less sleep need and are more resistant to negative effects of sleep loss. We investigated this using a cross-sectional and longitudinal sample of 47,029 participants of both sexes (20–89 years) from the Lifebrain consortium, Human Connectome project (HCP) and UK Biobank (UKB), with measures of self-reported sleep, including 51,295 MRIs of the brain and cognitive tests. A total of 740 participants who reported to sleep <6 h did not experience daytime sleepiness or sleep problems/disturbances interfering with falling or staying asleep. These short sleepers showed significantly larger regional brain volumes than both short sleepers with daytime sleepiness and sleep problems (n = 1742) and participants sleeping the recommended 7–8 h (n = 3886). However, both groups of short sleepers showed slightly lower general cognitive function (GCA), 0.16 and 0.19 SDs, respectively. Analyses using accelerometer-estimated sleep duration confirmed the findings, and the associations remained after controlling for body mass index, depression symptoms, income, and education. The results suggest that some people can cope with less sleep without obvious negative associations with brain morphometry and that sleepiness and sleep problems may be more related to brain structural differences than duration. However, the slightly lower performance on tests of general cognitive abilities warrants closer examination in natural settings. SIGNIFICANCE STATEMENT Short habitual sleep is prevalent, with unknown consequences for brain health and cognitive performance. Here, we show that daytime sleepiness and sleep problems are more strongly related to regional brain volumes than sleep duration. However, participants sleeping ≤6 h had slightly lower scores on tests of general cognitive function (GCA). This indicates that sleep need is individual and that sleep duration per se is very weakly if at all related brain health, while daytime sleepiness and sleep problems may show somewhat stronger associations. The association between habitual short sleep and lower scores on tests of general cognitive abilities must be further scrutinized in natural settings.
{"title":"Is Short Sleep Bad for the Brain? Brain Structure and Cognitive Function in Short Sleepers","authors":"A. Fjell, Øystein Sørensen, Yunpeng Wang, I. Amlien, W. Baaré, D. Bartrés-Faz, C. Boraxbekk, A. Brandmaier, I. Demuth, C. Drevon, Klaus P. Ebmeier, P. Ghisletta, R. Kievit, S. Kühn, K. S. Madsen, L. Nyberg, C. Solé-Padullés, D. Vidal-Piñeiro, G. Wagner, L. O. Watne, K. Walhovd","doi":"10.1101/2022.12.22.521614","DOIUrl":"https://doi.org/10.1101/2022.12.22.521614","url":null,"abstract":"Many sleep less than recommended without experiencing daytime sleepiness. According to prevailing views, short sleep increases risk of lower brain health and cognitive function. Chronic mild sleep deprivation could cause undetected sleep debt, negatively affecting cognitive function and brain health. However, it is possible that some have less sleep need and are more resistant to negative effects of sleep loss. We investigated this using a cross-sectional and longitudinal sample of 47,029 participants of both sexes (20–89 years) from the Lifebrain consortium, Human Connectome project (HCP) and UK Biobank (UKB), with measures of self-reported sleep, including 51,295 MRIs of the brain and cognitive tests. A total of 740 participants who reported to sleep <6 h did not experience daytime sleepiness or sleep problems/disturbances interfering with falling or staying asleep. These short sleepers showed significantly larger regional brain volumes than both short sleepers with daytime sleepiness and sleep problems (n = 1742) and participants sleeping the recommended 7–8 h (n = 3886). However, both groups of short sleepers showed slightly lower general cognitive function (GCA), 0.16 and 0.19 SDs, respectively. Analyses using accelerometer-estimated sleep duration confirmed the findings, and the associations remained after controlling for body mass index, depression symptoms, income, and education. The results suggest that some people can cope with less sleep without obvious negative associations with brain morphometry and that sleepiness and sleep problems may be more related to brain structural differences than duration. However, the slightly lower performance on tests of general cognitive abilities warrants closer examination in natural settings. SIGNIFICANCE STATEMENT Short habitual sleep is prevalent, with unknown consequences for brain health and cognitive performance. Here, we show that daytime sleepiness and sleep problems are more strongly related to regional brain volumes than sleep duration. However, participants sleeping ≤6 h had slightly lower scores on tests of general cognitive function (GCA). This indicates that sleep need is individual and that sleep duration per se is very weakly if at all related brain health, while daytime sleepiness and sleep problems may show somewhat stronger associations. The association between habitual short sleep and lower scores on tests of general cognitive abilities must be further scrutinized in natural settings.","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"2 1","pages":"5241 - 5250"},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91122193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-21DOI: 10.1101/2022.12.21.521303
Julie-Anne Balouek, Christabel Mclain, Adelaide R Minerva, Rebekah L. Rashford, Shannon N. Bennett, C. Peña
Early-life stress (ELS) is one of the strongest lifetime risk factors for depression, anxiety, suicide, and other psychiatric disorders, particularly after facing additional stressful events later in life. Human and animal studies demonstrate that ELS sensitizes individuals to subsequent stress. However, the neurobiological basis of such stress sensitization remains largely unexplored. We hypothesized that ELS-induced stress sensitization would be detectable at the level of neuronal ensembles, such that cells activated by ELS would be more reactive to adult stress. To test this, we leveraged transgenic mice to genetically tag, track, and manipulate experience-activated neurons. We found that in both male and female mice, ELS-activated neurons within the nucleus accumbens (NAc), and to a lesser extent the medial prefrontal cortex, were preferentially reactivated by adult stress. To test whether reactivation of ELS-activated ensembles in the NAc contributes to stress hypersensitivity, we expressed hM4Dis receptor in control or ELS-activated neurons of pups and chemogenetically inhibited their activity during experience of adult stress. Inhibition of ELS-activated NAc neurons, but not control-tagged neurons, ameliorated social avoidance behavior following chronic social defeat stress in males. These data provide evidence that ELS-induced stress hypersensitivity is encoded at the level of corticolimbic neuronal ensembles. SIGNIFICANCE STATEMENT Early-life stress enhances sensitivity to stress later in life, yet the mechanisms of such stress sensitization are largely unknown. Here, we show that neuronal ensembles in corticolimbic brain regions remain hypersensitive to stress across the life span, and quieting these ensembles during experience of adult stress rescues stress hypersensitivity.
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Pub Date : 2022-12-14DOI: 10.1523/JNEUROSCI.twij.42.50.2022
{"title":"This Week in The Journal","authors":"","doi":"10.1523/JNEUROSCI.twij.42.50.2022","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.twij.42.50.2022","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"116 1","pages":"9293 - 9293"},"PeriodicalIF":0.0,"publicationDate":"2022-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73480227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-07DOI: 10.1523/JNEUROSCI.twij.42.49.2022
{"title":"This Week in The Journal","authors":"","doi":"10.1523/JNEUROSCI.twij.42.49.2022","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.twij.42.49.2022","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"42 1","pages":"9097 - 9097"},"PeriodicalIF":0.0,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79373795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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