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Samer Siwani, Arthur S C França, Sanja Mikulovic, Amilcar Reis, Markus M Hilscher, Steven J Edwards, Richardson N Leão, Adriano B L Tort, Klas Kullander
Inhibitory interneurons participate in mnemonic processes. However, defined roles for identified interneuron populations are scarce. A subpopulation of oriens lacunosum-moleculare (OLM) interneurons genetically defined by the expression of the nicotinic receptor α2 subunit has been shown to gate information carried by either the temporoammonic pathway or Schaffer collaterals in vitro. Here we set out to determine whether selective modulation of OLMα2 cells in the intermediate CA1 affects learning and memory in vivo...
June 29, 2018: Neuron
Federico W Grillo, Guilherme Neves, Alison Walker, Gema Vizcay-Barrena, Roland A Fleck, Tiago Branco, Juan Burrone
How presynaptic inputs and neurotransmitter release dynamics are distributed along a dendritic tree is not well established. Here, we show that presynaptic boutons that form onto basal dendrites of CA1 pyramidal neurons display a decrease in active zone (AZ) size with distance from the soma, resulting in a distance-dependent increase in short-term facilitation. Our findings suggest that the spatial distribution of short-term facilitation serves to compensate for the electrotonic attenuation of subthreshold distal inputs during repeated stimulation and fine-tunes the preferred input frequency of dendritic domains...
June 28, 2018: Neuron
Stephen X Zhang, Lauren E Miner, Christine L Boutros, Dragana Rogulja, Michael A Crickmore
We reveal a central role for chance neuronal events in the decision of a male fly to court, which can be modeled as a coin flip with odds set by motivational state. The decision is prompted by a tap of a female with the male's pheromone-receptor-containing foreleg. Each tap evokes competing excitation and inhibition onto P1 courtship command neurons. A motivating dopamine signal desensitizes P1 to the inhibition, increasing the fraction of taps that successfully initiate courtship. Once courtship has begun, the same dopamine tone potentiates recurrent excitation of P1, maintaining the courtship of highly motivated males for minutes and buffering against termination...
June 28, 2018: Neuron
Lucy A L Heap, Gilles Vanwalleghem, Andrew W Thompson, Itia A Favre-Bulle, Ethan K Scott
Looming visual stimuli result in escape responses that are conserved from insects to humans. Despite their importance for survival, the circuits mediating visual startle have only recently been explored in vertebrates. Here we show that the zebrafish thalamus is a luminance detector critical to visual escape. Thalamic projection neurons deliver dim-specific information to the optic tectum, and ablations of these projections disrupt normal tectal responses to looms. Without this information, larvae are less likely to escape from dark looming stimuli and lose the ability to escape away from the source of the loom...
June 28, 2018: Neuron
Charuta Gavankar Furey, Jungmin Choi, Sheng Chih Jin, Xue Zeng, Andrew T Timberlake, Carol Nelson-Williams, M Shahid Mansuri, Qiongshi Lu, Daniel Duran, Shreyas Panchagnula, August Allocco, Jason K Karimy, Arjun Khanna, Jonathan R Gaillard, Tyrone DeSpenza, Prince Antwi, Erin Loring, William E Butler, Edward R Smith, Benjamin C Warf, Jennifer M Strahle, David D Limbrick, Phillip B Storm, Gregory Heuer, Eric M Jackson, Bermans J Iskandar, James M Johnston, Irina Tikhonova, Christopher Castaldi, Francesc López-Giráldez, Robert D Bjornson, James R Knight, Kaya Bilguvar, Shrikant Mane, Seth L Alper, Shozeb Haider, Bulent Guclu, Yasar Bayri, Yener Sahin, Michael L J Apuzzo, Charles C Duncan, Michael L DiLuna, Murat Günel, Richard P Lifton, Kristopher T Kahle
Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted mutations: TRIM71 (p = 2.15 × 10-7 ), SMARCC1 (p = 8.15 × 10-10 ), and PTCH1 (p = 1.06 × 10-6 )...
June 28, 2018: Neuron
Anna Schroeder, Jeroen Vanderlinden, Katlijn Vints, Luís F Ribeiro, Kristel M Vennekens, Natalia V Gounko, Keimpe D Wierda, Joris de Wit
Pyramidal neurons express rich repertoires of leucine-rich repeat (LRR)-containing adhesion molecules with similar synaptogenic activity in culture. The in vivo relevance of this molecular diversity is unclear. We show that hippocampal CA1 pyramidal neurons express multiple synaptogenic LRR proteins that differentially distribute to the major excitatory inputs on their apical dendrites. At Schaffer collateral (SC) inputs, FLRT2, LRRTM1, and Slitrk1 are postsynaptically localized and differentially regulate synaptic structure and function...
June 27, 2018: Neuron
Kaushik J Lakshminarasimhan, Marina Petsalis, Hyeshin Park, Gregory C DeAngelis, Xaq Pitkow, Dora E Angelaki
Path integration is a strategy by which animals track their position by integrating their self-motion velocity. To identify the computational origins of bias in visual path integration, we asked human subjects to navigate in a virtual environment using optic flow and found that they generally traveled beyond the goal location. Such a behavior could stem from leaky integration of unbiased self-motion velocity estimates or from a prior expectation favoring slower speeds that causes velocity underestimation...
June 20, 2018: Neuron
Alicia Che, Rachel Babij, Andrew F Iannone, Robert N Fetcho, Monica Ferrer, Conor Liston, Gord Fishell, Natalia V De Marco García
The neonatal mammal faces an array of sensory stimuli when diverse neuronal types have yet to form sensory maps. How these inputs interact with intrinsic neuronal activity to facilitate circuit assembly is not well understood. By using longitudinal calcium imaging in unanesthetized mouse pups, we show that layer I (LI) interneurons, delineated by co-expression of the 5HT3a serotonin receptor (5HT3aR) and reelin (Re), display spontaneous calcium transients with the highest degree of synchrony among cell types present in the superficial barrel cortex at postnatal day 6 (P6)...
June 19, 2018: Neuron
Eric Lowet, Bruno Gomes, Karthik Srinivasan, Huihui Zhou, Robert John Schafer, Robert Desimone
Attention can be "covertly" directed without eye movements; yet, even during fixation, there are continuous microsaccades (MSs). In areas V4 and IT of macaques, we found that firing rates and stimulus representations were enhanced by attention but only following a MS toward the attended stimulus. The onset of neural attentional modulations was tightly coupled to the MS onset. The results reveal a major link between the effects of covert attention on cortical visual processing and the overt movement of the eyes...
June 16, 2018: Neuron
Antonia Drinnenberg, Felix Franke, Rei K Morikawa, Josephine Jüttner, Daniel Hillier, Peter Hantz, Andreas Hierlemann, Rava Azeredo da Silveira, Botond Roska
Many brain regions contain local interneurons of distinct types. How does an interneuron type contribute to the input-output transformations of a given brain region? We addressed this question in the mouse retina by chemogenetically perturbing horizontal cells, an interneuron type providing feedback at the first visual synapse, while monitoring the light-driven spiking activity in thousands of ganglion cells, the retinal output neurons. We uncovered six reversible perturbation-induced effects in the response dynamics and response range of ganglion cells...
June 15, 2018: Neuron
Ravi L Rungta, Emmanuelle Chaigneau, Bruno-Félix Osmanski, Serge Charpak
Functional hyperemia, a regional increase of blood flow triggered by local neural activation, is used to map brain activity in health and disease. However, the spatial-temporal dynamics of functional hyperemia remain unclear. Two-photon imaging of the entire vascular arbor in NG2-creERT2;GCaMP6f mice shows that local synaptic activation, measured via oligodendrocyte precursor cell (OPC) Ca2+ signaling, generates a synchronous Ca2+ drop in pericytes and smooth muscle cells (SMCs) enwrapping all upstream vessels feeding the activated synapses...
June 15, 2018: Neuron
Ben Readhead, Jean-Vianney Haure-Mirande, Cory C Funk, Matthew A Richards, Paul Shannon, Vahram Haroutunian, Mary Sano, Winnie S Liang, Noam D Beckmann, Nathan D Price, Eric M Reiman, Eric E Schadt, Michelle E Ehrlich, Sam Gandy, Joel T Dudley
Investigators have long suspected that pathogenic microbes might contribute to the onset and progression of Alzheimer's disease (AD) although definitive evidence has not been presented. Whether such findings represent a causal contribution, or reflect opportunistic passengers of neurodegeneration, is also difficult to resolve. We constructed multiscale networks of the late-onset AD-associated virome, integrating genomic, transcriptomic, proteomic, and histopathological data across four brain regions from human post-mortem tissue...
June 14, 2018: Neuron
Ulises Pereira, Nicolas Brunel
The attractor neural network scenario is a popular scenario for memory storage in the association cortex, but there is still a large gap between models based on this scenario and experimental data. We study a recurrent network model in which both learning rules and distribution of stored patterns are inferred from distributions of visual responses for novel and familiar images in the inferior temporal cortex (ITC). Unlike classical attractor neural network models, our model exhibits graded activity in retrieval states, with distributions of firing rates that are close to lognormal...
June 13, 2018: Neuron
Sang Min Park, Jae Seok Lim, Suresh Ramakrishina, Se Hoon Kim, Woo Kyeong Kim, Junehawk Lee, Hoon-Chul Kang, Jeremy F Reiter, Dong Seok Kim, Hyongbum Henry Kim, Jeong Ho Lee
Focal malformations of cortical development (FMCDs), including focal cortical dysplasia (FCD) and hemimegalencephaly (HME), are major etiologies of pediatric intractable epilepsies exhibiting cortical dyslamination. Brain somatic mutations in MTOR have recently been identified as a major genetic cause of FMCDs. However, the molecular mechanism by which these mutations lead to cortical dyslamination remains poorly understood. Here, using patient tissue, genome-edited cells, and mouse models with brain somatic mutations in MTOR, we discovered that disruption of neuronal ciliogenesis by the mutations underlies cortical dyslamination in FMCDs...
June 9, 2018: Neuron
James M Jeanne, Mehmet Fişek, Rachel I Wilson
Each odorant receptor corresponds to a unique glomerulus in the brain. Projections from different glomeruli then converge in higher brain regions, but we do not understand the logic governing which glomeruli converge and which do not. Here, we use two-photon optogenetics to map glomerular connections onto neurons in the lateral horn, the region of the Drosophila brain that receives the majority of olfactory projections. We identify 39 morphological types of lateral horn neurons (LHNs) and show that different types receive input from different combinations of glomeruli...
June 8, 2018: Neuron
Xiang-Ping Yao, Xuewen Cheng, Chong Wang, Miao Zhao, Xin-Xin Guo, Hui-Zhen Su, Lu-Lu Lai, Xiao-Huan Zou, Xue-Jiao Chen, Yuying Zhao, En-Lin Dong, Ying-Qian Lu, Shuang Wu, Xiaojuan Li, Gaofeng Fan, Hongjie Yu, Jianfeng Xu, Ning Wang, Zhi-Qi Xiong, Wan-Jin Chen
Primary familial brain calcification (PFBC) is a genetically heterogeneous disorder characterized by bilateral calcifications in the basal ganglia and other brain regions. The genetic basis of this disorder remains unknown in a significant portion of familial cases. Here, we reported a recessive causal gene, MYORG, for PFBC. Compound heterozygous or homozygous mutations of MYORG co-segregated completely with PFBC in six families, with logarithm of odds (LOD) score of 4.91 at the zero recombination fraction...
June 6, 2018: Neuron
Han Qin, Ling Fu, Bo Hu, Xiang Liao, Jian Lu, Wenjing He, Shanshan Liang, Kuan Zhang, Ruijie Li, Jiwei Yao, Junan Yan, Hao Chen, Hongbo Jia, Benedikt Zott, Arthur Konnerth, Xiaowei Chen
The ability to remember and to navigate to safe places is necessary for survival. Place navigation is known to involve medial entorhinal cortex (MEC)-hippocampal connections. However, learning-dependent changes in neuronal activity in the distinct circuits remain unknown. Here, by using optic fiber photometry in freely behaving mice, we discovered the experience-dependent induction of a persistent-task-associated (PTA) activity. This PTA activity critically depends on learned visual cues and builds up selectively in the MEC layer II-dentate gyrus, but not in the MEC layer III-CA1 pathway, and its optogenetic suppression disrupts navigation to the target location...
June 5, 2018: Neuron
Ching-Lung Hsu, Xinyu Zhao, Aaron D Milstein, Nelson Spruston
The mammalian hippocampus forms a cognitive map using neurons that fire according to an animal's position ("place cells") and many other behavioral and cognitive variables. The responses of these neurons are shaped by their presynaptic inputs and the nature of their postsynaptic integration. In CA1 pyramidal neurons, spatial responses in vivo exhibit a strikingly supralinear dependence on baseline membrane potential. The biophysical mechanisms underlying this nonlinear cellular computation are unknown...
June 5, 2018: Neuron
Joanna I Giza, Jihye Kim, Heidi C Meyer, Agustin Anastasia, Iva Dincheva, Crystal I Zheng, Katherine Lopez, Henrietta Bains, Jianmin Yang, Clay Bracken, Conor Liston, Deqiang Jing, Barbara L Hempstead, Francis S Lee
A human variant in the BDNF gene (Val66Met; rs6265) is associated with impaired fear extinction. Using super-resolution imaging, we demonstrate that the BDNF Met prodomain disassembles dendritic spines and eliminates synapses in hippocampal neurons. In vivo, ventral CA1 (vCA1) hippocampal neurons undergo similar morphological changes dependent on their transient co-expression of a SorCS2/p75NTR receptor complex during peri-adolescence. BDNF Met prodomain infusion into the vCA1 during this developmental time frame reduces dendritic spine density and prelimbic (PL) projections, impairing cued fear extinction...
June 2, 2018: Neuron
Honghui Zhang, Andrew J Watrous, Ansh Patel, Joshua Jacobs
Human cognition requires the coordination of neural activity across widespread brain networks. Here, we describe a new mechanism for large-scale coordination in the human brain: traveling waves of theta and alpha oscillations. Examining direct brain recordings from neurosurgical patients performing a memory task, we found contiguous clusters of cortex in individual patients with oscillations at specific frequencies within 2 to 15 Hz. These oscillatory clusters displayed spatial phase gradients, indicating that they formed traveling waves that propagated at ∼0...
June 1, 2018: Neuron
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