Impairments of glutamatergic synaptic transmission in Alzheimer’s disease
Benedikt Zott, Arthur Konnerth
One of the hallmarks of Alzheimer’s disease (AD) is structural cell damage and neuronal death in the brains of affected individuals. As these changes are irreversible, it is important to understand their origins and precursors in order to develop treatment strategies against AD. Here, we revie ...
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REM sleep-active hypothalamic neurons may contribute to hippocampal social-memory consolidation
Han Qin, Ling Fu, Tingliang Jian, Hongbo Jia, Arthur Konnerth, Xiaowei Chen
The hippocampal CA2 region plays a key role in social memory. The encoding of such memory involves afferent activity from the hypothalamic supramammillary nucleus (SuM) to CA2. However, the neuronal circuits required for consolidation of freshly encoded social memory remain unknown. Here, we used ci ...
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Glutamate indicators with improved activation kinetics and localization for imaging synaptic transmission
Abhi Aggarwal,Liu,Chen,Ralowicz,Bergerson,Tomaska,Hanson,Hasseman,Reep,Tsegaye,Yao,Ji,Kloos,Deepika,Walpita,Patel,Tilberg,Mohar,Jooger,Hoppa,Arthur Konnerth,Kleinfeld,Schreiter,Kaspar Podgorski
The fluorescent glutamate indicator iGluSnFR enables imaging of neurotransmission with genetic and molecular specificity. However, existing iGluSnFR variants exhibit saturating activation kinetics and are excluded from post-synaptic densities, limiting their ability to distinguish synaptic from ex ...
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Fear learning induces α7-nicotinic acetylcholine receptor-mediated astrocytic responsiveness that is required for memory persistence
Kuan Zhang,R.Förster,He1,Liao,Li1,Yang,Qin4,Wang,Ding,Li1,Jian1,Wang1,Zhang,Yang,Jin,Zhang,Qin6,Lu,Chen,Stobart,Weber,Adelsberger,Arthur Konnerth,Xiaowei Chen
nature neuroscience
Memory persistence is a fundamental cognitive process for guiding behaviors and is considered to rely mostly on neuronal and synaptic plasticity. Whether and how astrocytes contribute to memory persistence is largely unknown. Here, by using two-photon Ca2+ imaging in head-fixed mice and fiber ph ...
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Population imaging of synaptically released glutamate in mouse hippocampal slices
Felix Unger, Arthur Konnerth, Benedikt Zott
STAR Protoc
Glutamatergic neurotransmission is a widespread form of synaptic excitation i the mammalian brain. The development of genetically encoded fluorescent glutamate sensors allows monitoring synaptic signaling in living brain tissue in real time. Here, we describe single- and two-photon imaging of synapt ...
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Single-neuron representation of learned complexsounds in the auditory cortex
Meng Wang,Liao,Li,Liang,Ding,J.Li,Zhang,He,Ke Liu,JPan,Zhao,Li,Kuan Zhang,X.Li,Lyu,Z.Zhou,Zsuzsanna Varga,Y.Mi,Y.Zhou,J.Yan,S.Zeng,K.Liu,Arthur Konnerth,Israel Nelken,Hongbo Jia,Xiaowei Chen
Nature Communications
The sensory responses of cortical neuronal populations following training have been exten-sively studied. However, the spikefiring properties of individual cortical neurons followingtraining remain unknown. Here, we have combined two-photon Ca2+imaging and single-cellelectrophysiology in awake behav ...
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A vicious cycle of β amyloid–dependent neuronal hyperactivation
Benedikt Zott,Manuel M. Simon,Wei Hong, Felix Unger,Hsing-Jung Chen-Engerer,Matthew P. Frosch,Bert Sakmann,Dominic M. Walsh,Arthur Konnerth
β-amyloid (Aβ )–dependent neuronal hyperactivity is believed to contribute to the circuit dysfunction that characterizes the early stages of Alzheimer’s disease (AD). Although experimental evidence in support of this hypothesis continues to accrue, the underlying pathological mechanism ...
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Two types of functionally distinct Ca2+ stores in hippocampal neurons
Hsing-Jung Chen-Engerer, Jana Hartmann, Rosa Maria Karl, Jun Yang, Stefan Feske, Arthur Konnerth
Nature Communication
It is widely assumed that inositol trisphosphate (IP3) and ryanodine (Ry) receptors share the same Ca2+ pool in central mammalian neurons. We now demonstrate that in hippocampal CA1 pyramidal neurons IP3- and Ry-receptors are associated with two functionally distinct intracellular Ca2+ stores, respe ...
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High-performance calcium sensors for imaging activity in neuronal populations and microcompartments
H.Dana,Yi Sun,B. Mohar,K. Hulse,A. M. Kerlin,J.P. Hasseman,G. Tsegaye, A. Tsang,A. Wong,R. Patel,J.J. Macklin,Y. Chen,A. Konnerth,V. Jayaraman,L.L. Looger,E.R. Schreiter, K. Svoboda,D.S. Kim
Nature Methods
Calcium imaging with genetically encoded calcium indicators (GECIs) is routinely used to measure neural activity in intact nervous systems. GECIs are frequently used in one of two different modes: to track activity in large populations of neuronal cell bodies, or to follow dynamics in subcellular ...
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Abolishing cAMP sensitivity in HCN2 pacemaker channels induces generalized seizures
V. Hammelmann,M. S. Stieglitz,.H. Hülle,K. Le Meur,J. Kass,M Brümmer,C Gruner,R. D.Rötzer,S Fenske,J. Hartmann,B. Zott,A. Lüthi,S. Spahn,M Moser,D. Isbrandt,A. Ludwig,A. Konnerth,C Wahl-Schott,M. Biel
JCI insight
Hyperpolarization-activated cyclic nucleotide–gated (HCN) channels are dually gated channels that are operated by voltage and by neurotransmitters via the cAMP system. cAMP-dependent HCN regulation has been proposed to play a key role in regulating circuit behavior in the thalamus. By analyzing a ...
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In Vivo Functional Mapping of a Cortical Column at Single-Neuron Resolution
Carsten H. Tischbirek, Takahiro Noda, Manabu Tohmi, Antje Birkner, Israel Nelken, Arthur Konnerth
Cell Reports
The cerebral cortex is organized in vertical columns that contain neurons with similar functions. The cellular micro-architecture of such columns is an essential determinant of brain dynamics and cortical information processing. However, a detailed understanding of columns is incomplete, even i ...
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What Happens with the Circuit in Alzheimers Disease in Mice and Humans?
Benedikt Zott, Marc Aurel Busche, Reisa A. Sperling, Arthur Konnerth
Annual Review of Neuroscience
A major mystery of many types of neurological and psychiatric disorders, such as Alzheimers disease (AD), remains the underlying, disease-specific neuronal damage. Because of the strong interconnectivity of neurons in the brain, neuronal dysfunction necessarily disrupts neuronal circuits. In this ...
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A Visual-Cue-Dependent Memory Circuit for Place Navigation
Han Qin , Ling Fu , 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 ...
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BACE inhibition-dependent repair of Alzheimer´s pathophysiology
Keskin AD, Kekus M, Adelsberger H, Neumann U, Shimshek DR, Song B, Zott B, Peng T, Foerstl H, Staufenbiel M, Nelken I, Sakmann B, Konnerth A, Busche MA
Proc Natl Acad Sci U S A
Amyloid-ß (Aß) is thought to play an essential pathogenic role in Alzheimers disease (AD). A key enzyme involved in the generation of Aß is the ß-secretase BACE, for which powerful inhibitors have been developed and are currently in use in human clinical trials. However, although BACE inhibition ...
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Improved deep two-photon calcium imaging in vivo
Birkner A, Tischbirek CH, Konnerth A
Cell Calcium
Two-photon laser scanning calcium imaging has emerged as a useful method for the exploration of neural function and structure at the cellular and subcellular level in vivo. The applications range from imaging of subcellular compartments such as dendrites, spines and axonal boutons up to the function ...
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Cell-type-speci?c modulation of targets and distractors by dopamine D1 receptors in primate prefrontal cortex
Simon N. Jacob, Maximilian Stalter, Andreas Nieder
Nature Communications
The prefrontal cortex (PFC) is crucial for maintaining relevant information in working memory and resisting interference. PFC neurons are strongly regulated by dopamine, but it is unknown whether dopamine receptors are involved in protecting target memories from distracting stimuli. We investigated ...
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In vivo deep two-photon imaging of neural circuits with the fluorescent Ca2+ indicator Cal-590
Tischbirek C, Birkner A, Konnerth A
J Physiol
In vivo two-photon Ca2+ imaging has become an effective approach for the functional analysis of neuronal populations, individual neurons and subcellular neuronal compartments in the intact brain. When imaging individually labelled neurons, depth penetration can often reach up to 1 mm below the corti ...
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Cortical Sensory Responses Are Enhanced by the Higher-Order Thalamus
Rebecca A. Mease , Markus Metz , Alexander Groh
Cell Reports
Mease et al. investigate a major, yet puzzling, thalamocortical pathway from the higher-order thalamus to the cortex. This pathway enhances sensory responses in layer 5 cortical neurons on fast and slow timescales. Such enhancement of cortical responses by higher-order thalamocortical inputs may ser ...
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Decreased amyloid-β and increased neuronal hyperactivity by immunotherapy in Alzheimers models
Marc Aurel Busche, Christine Grienberger, Aylin D Keskin, Beomjong Song, Ulf Neumann, Matthias Staufenbiel, Hans Förstl, Arthur Konnerth
Nature Neuroscience
Among the most promising approaches for treating Alzheimer´s disease is immunotherapy with amyloid-Beta (ABeta)-targeting antibodies. Using in vivo two-photon imaging in mouse models, we found that two different antibodies to ABeta used for treatment were ineffective at repairing neuronal dysfuncti ...
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eta-Secretase processing of APP inhibits neuronal activity in the hippocampus
M.Willem, Tahirovic, Busche, Ovsepian, Chafai, Kootar, Hornburg, Evans, Moore, Daria, Hampel, Mueller, Giudici, Nuscher, Kremmer, Heneka, Thal, Lannfelt, Mueller, Livesey, Meissner, Herms, Konnerth, M
Nature | Letter
Alzheimer disease (AD) is characterized by the accumulation of amyloid plaques, which are predominantly composed of amyloid-b peptide1. Two principal physiological pathways either prevent or promote amyloid-b generation from its precursor, b-amyloid precursor protein (APP), in a competitive mann ...
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Rescue of long-range circuit dysfunction in Alzheimer’s disease models
Marc Aurel Busche, Maja Kekuš, Helmuth Adelsberger, Takahiro Noda, Hans Förstl, Israel Nelken, Arthur Konnerth
Nature Neuroscience
Alzheimer’s disease (AD) is associated with defects of synaptic connectivity. Such defects may not be restricted to local neuronal interactions but may extend to long-range brain activities, such as slow-wave oscillations that are particularly prominent during non–rapid eye movement (non-REM) ...
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Deep two-photon brain imaging with a red-shifted fluorometric Ca2+ indicator
Carsten Tischbirek*, Antje Birkner*, Hongbo Jia, Bert Sakmann, Arthur Konnerth
In vivo Ca2+ imaging of neuronal populations in deep cortical layers has remained a major challenge, as the recording depth of two-photon microscopy is limited because of the scattering and absorption of photons in brain tissue. A possible strategy to increase the imaging depth is the use of red ...
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TRPC3‐dependent synaptic transmission in central mammalian neurons
Jana Hartmann, Arthur Konnerth
The transient receptor potential (TRPC) proteins form non-selective cation channels that are activated downstream of Gq-phospholipase C-coupled receptors. TRPC3, one of the seven members of the TRPC subfamily, combines functions of an unspecific ion channel and a signal transducer. In the mamma ...
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Dendritic function in vivo
Christine Grienberger, Xiaowei Chen, Arthur Konnerth
Trends in Neurosciences
Dendrites are the predominant entry site for excitatory synaptic potentials in most types of central neurons. There is increasing evidence that dendrites are not just passive transmitting devices but play active roles in synaptic integration through linear and non-linear mechanisms. Frequently, ...
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Context-dependent coding in single neurons
Rebecca A. Mease, SangWook Lee, Anna T. Moritz, Randall K. Powers, Marc D. Binder, Adrienne L. Fairhall
J Comput Neurosci
The linear-nonlinear cascade model (LN model) has proven very useful in representing a neural system?s encoding properties, but has proven less successful in reproducing the firing patterns of individual neurons whose behavior is strongly dependent on prior firing history. While the cell?s behav ...
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Intrinsic neuronal properties switch the mode of information transmission in networks.
Gjorgjieva J, Mease RA, Moody WJ, Fairhall AL
PLoS Comput Biol.
Diverse ion channels and their dynamics endow single neurons with complex biophysical properties. These properties determine the heterogeneity of cell types that make up the brain, as constituents of neural circuits tuned to perform highly specific computations. How do biophysical properties of sing ...
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An assay to image neuronal microtubule dynamics in mice
Tatjana Kleele, P. Marinkovi, P. Williams, S.Stern,E. Weigand, P. Engerer, R. Naumann, J. Hartmann, R. Karl, F. Bradke, D. Bishop, J. Herms, A. Konnerth, M. Kerschensteiner, L. Godinho, T. Misgeld
Nature Communikation
Microtubule dynamics in neurons play critical roles in physiology, injury and disease and determine microtubule orientation, the cell biological correlate of neurite polarization. Several microtubule binding proteins, including end-binding protein 3 (EB3), specifically bind to the growing plus ti ...
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Linear integration of spine Ca2+ signals in layer 4 cortical neurons in vivo
Jia H, Varga Z, Sakmann B, Konnerth A
Proc Natl Acad Sci U S A
Sensory information reaches the cortex through synchronously active thalamic axons, which provide a strong drive to layer 4 (L4) cortical neurons. Because of technical limitations, the dendritic signaling processes underlying the rapid and efficient activation of L4 neurons in vivo remained unknown. ...
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STIM1 Controls Neuronal Ca2+ Signaling, mGluR1-dependent synaptic transmission, and cerebellar motor behavior
Hartmann J, Karl RM, Alexander RP, Adelsberger H, Brill MS, Rühlmann C, Ansel A, Sakimura K, Baba Y, Kurosaki T, Misgeld T, Konnerth A
In central mammalian neurons, activation of metabotropic glutamate receptor type1 (mGluR1) evokes a complex synaptic response consisting of IP3 receptor-dependent Ca(2+) release from internal Ca(2+) stores and a slow depolarizing potential involving TRPC3 channels. It is largely unclear how mGluR1 i ...
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Cortical control of adaptation and sensory relay mode in the thalamus
Mease RA, Krieger P, Groh A
Proc Natl Acad Sci U S A
A major synaptic input to the thalamus originates from neurons in cortical layer 6 (L6); however, the function of this cortico-thalamic pathway during sensory processing is not well understood. In the mouse whisker system, we found that optogenetic stimulation of L6 in vivo results in a mixture of h ...
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NMDA Receptor-Dependent Multidendrite Ca2+ Spikes Required for Hippocampal Burst Firing In Vivo
Grienberger C, Chen X, Konnerth A.
High-frequency bursts of action potentials (APs) are a distinctive form of signaling in various types of mammalian central neurons. In CA1 hippocampal pyramidal neurons in vivo, such complex spike bursts (CSs) are detected during various behaviors and are considered to be particularly important for ...
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Local domains of motor cortical activity revealed by fiber-optic calcium recordings in behaving nonhuman primates
Adelsberger H, Zainos A, Alvarez M, Romo R, Konnerth A.
Proc Natl Acad Sci U S A
Brain mapping experiments involving electrical microstimulation indicate that the primary motor cortex (M1) directly regulates muscle contraction and thereby controls specific movements. Possibly, M1 contains a small circuit "map" of the body that is formed by discrete local networks that code for s ...
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Emergence of adaptive computation by single neurons in the developing cortex.
Mease RA, Famulare M, Gjorgjieva J, Moody WJ, Fairhall AL.
J Neurosci.
Adaptation is a fundamental computational motif in neural processing. To maintain stable perception in the face of rapidly shifting input, neural systems must extract relevant information from background fluctuations under many different contexts. Many neural systems are able to adjust their Input o ...
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Multibranch activity in basal and tuft dendrites during firing of layer 5 cortical neurons in vivo.
Hill DN, Varga Z, Jia H, Sakmann B, Konnerth A.
Proc Natl Acad Sci U S A.
Layer 5 pyramidal neurons process information from multiple cortical layers to provide a major output of cortex. Because of technical limitations it has remained unclear how these cells integrate widespread synaptic inputs located in distantly separated basal and tuft dendrites. Here, we obtained in ...
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Convergence of Cortical and Sensory Driver Inputs on Single Thalamocortical Cells
Groh A*, Bokor H*, Mease RA, Plattner VM, Hangya B, Stroh A, Deschenes M, Acsády L.*Co-first authors
Cerebral Cortex
Ascending and descending information is relayed through the thalamus via strong, “driver” pathways. According to our current knowledge, different driver pathways are organized in parallel streams and do not interact at the thalamic level. Using an electron microscopic approach combined with opto ...
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Reactivation of the Same Synapses during Spontaneous Up States and Sensory Stimuli
Chen X, Rochefort NL, Sakmann B, Konnerth A
Cell Rep.
In the mammalian brain, calcium signals in dendritic spines are involved in many neuronal functions, particularly in the induction of synaptic plasticity. Recent studies have identified sensory stimulation-evoked spine calcium signals in cortical neurons in vivo. However, spine signaling during ongo ...
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Making waves: initiation and propagation of corticothalamic ca(2+) waves in vivo.
Stroh A, Adelsberger H, Groh A, Rühlmann C, Fischer S, Schierloh A, Deisseroth K, Konnerth A.
Corticothalamic slow oscillations of neuronal activity determine internal brain states. At least in the cortex, the electrical activity is associated with large neuronal Ca(2+) transients. Here we implemented an optogenetic approach to explore causal features of the generation of slow oscillation-as ...
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In vivo imaging of disease-related mitochondrial dynamics in a vertebrate model system
Plucinska G*, Paquet, D*, Hruscha A, Godinho L, Haass C, Schmid B**, Misgeld T.** Co-first authors *, Co-senior authors**
Journal of Neuroscience
Mitochondria provide ATP, maintain calcium homeostasis, and regulate apoptosis. Neurons, due to their size and complex geometry, are particularly dependent on the proper functioning and distribution of mitochondria. Thus disruptions of these organelles and their transport play a central role in a br ...
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LOTOS-based two-photon calcium imaging of dendritic spines in vivo.
Chen X, Leischner U, Varga Z, Jia H, Deca D, Rochefort NL, Konnerth A.
Nat Protoc.
Neurons in the mammalian brain receive thousands of synaptic inputs on their dendrites. In many types of neurons, such as cortical pyramidal neurons, excitatory synapses are formed on fine dendritic protrusions called spines. Usually, an individual spine forms a single synaptic contact with an affer ...
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Dendritic spines: from structure to in vivo function
Rochefort NL, Konnerth A.
EMBO Rep. 2012 Aug 1;13(8):699-708
Dendritic spines arise as small protrusions from the dendritic shaft of various types of neuron and receive inputs from excitatory axons. Ever since dendritic spines were first described in the nineteenth century, questions about their function have spawned many hypotheses. In this review, we introd ...
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Critical role of soluble amyloid-β for early hippocampal hyperactivity in a mouse model of Alzheimers disease
Busche MA, Chen X, Henning HA, Reichwald J, Staufenbiel M, Sakmann B, Konnerth A.
Proc Natl Acad
Alzheimer's disease (AD) is characterized by a progressive dysfunction of central neurons. Recent experimental evidence indicates that in the cortex, in addition to the silencing of a fraction of neurons, other neurons are hyperactive in amyloid-β (Aβ) plaque-enriched regions. However, it ...
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Staged decline of neuronal function in vivo in an animal model of Alzheimers disease
Grienberger C.*, Rochefort N.L.*, Adelsberger H., Henning H.A., Hill D.N., Reichwald J., Staufenbiel M. and Konnerth A. *equal contribution
Nature Commun. 2012 Apr 10;3:774.
The accumulation of amyloid-β in the brain is an essential feature of Alzheimers disease. However, the impact of amyloid-β-accumulation on neuronal dysfunction on the single cell level in vivo is poorly understood. Here we investigate the progression of amyloid-β load in relation to n ...
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Imaging Calcium in Neurons
Christine Grienberger, Arthur Konnerth
Neuron. 2012 Mar 8;73(5):862-85.
Calcium ions generate versatile intracellular signals that control key functions in all types of neurons. Imaging calcium in neurons is particularly important because calcium signals exert their highly specific functions in well-defined cellular subcompartments. In this Primer, we briefly review the ...
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Sound-evoked network calcium transients in mouse auditory cortex in vivo
Grienberger C.*, Adelsberger H.*, Stroh A., Milos R.I., Garaschuk O., Schierloh A., Nelken I. and Konnerth A. *equal contribution
Journal of Physiology. 2012 Feb 15;590:899-918.
Population calcium signals generated by the action potential activity of local clusters of neurons have been recorded in the auditory cortex of mice using an optical fibre-based approach. These network calcium transients (NCaTs) occurred spontaneously as well as in response to sound stimulation. Two ...
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Axonal transport deficits and degeneration can evolve independently in mouse models of amyotrophic lateral sclerosis
Marinkoviæ P, Reuter MS, Brill MS, Godinho L, Kerschensteiner M* and Misgeld T*. *co-senior authors
Axonal transport deficits have been reported in many neurodegenerative conditions and are widely assumed to be an immediate causative step of axon and synapse loss. By imaging changes in axonal morphology and organelle transport over time in several animal models of amyotrophic lateral sclerosis (AL ...
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Development of direction selectivity in mouse cortical neurons
Rochefort NL*, Narushima M*, Grienberger C, Marandi N, Hill DN, Konnerth A. *equal contribution
Previous studies of the ferret visual cortex indicate that the development of direction selectivity requires visual experience. Here, we used two-photon calcium imaging to study the development of direction selectivity in layer 2/3 neurons of the mouse visual cortex in vivo. Surprisingly, just after ...
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Spatial constraints dictate glial territories at murine neuromuscular junctions.
Brill MS, Lichtman JW, Thompson W, Zuo Y*, Misgeld T*. *co-senior authors
J Cell Biol
Schwann cells (SCs), the glial cells of the peripheral nervous system, cover synaptic terminals, allowing them to monitor and modulate neurotransmission. Disruption of glial coverage leads to axon degeneration and synapse loss. The cellular mechanisms that establish and maintain this coverage remain ...
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B. Short

Dendritic coding of multiple sensory inputs in single cortical neurons in vivo
Zsuzsanna Varga, Hongbo Jia, Bert Sakmann, and Arthur Konnerth
Single cortical neurons in the mammalian brain receive signals arising from multiple sensory input channels. Dendritic integration of these afferent signals is critical in determining the amplitude and time course of the neurons output signals. As of yet, little is known about the spatial and tempor ...
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Functional mapping of single spines in cortical neurons in vivo.
Chen X, Leischner U, Rochefort NL, Nelken I, Konnerth A
The individual functional properties and spatial arrangement of afferent synaptic inputs on dendrites have a critical role in the processing of information by neurons in the mammalian brain. Although recent work has identified visually-evoked local dendritic calcium signals in the rodent visual cort ...
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Near-infrared branding efficiently correlates light and electron microscopy
Bishop D, Nikic I, Brinkoetter M, Knecht S, Potz S, Kerschensteiner M*, Misgeld T*. *Co-senior authors
Nature Methods
The correlation of light and electron microscopy of complex tissues remains a major challenge. Here we report near-infrared branding (NIRB), which facilitates such correlation by using a pulsed, near-infrared laser to create defined fiducial marks in three dimensions in fixed tissue. As these marks ...
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A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis
Nikic I, Merkler D, Sorbara C, Brinkoetter M, Kreutzfeldt M, Bareyre FM, Brück W, Bishop D, Misgeld T*, Kerschensteiner M*. *Co-senior authors
Nature Medicine
In multiple sclerosis, a common inflammatory disease of the central nervous system, immune-mediated axon damage is responsible for permanent neurological deficits. How axon damage is initiated is not known. Here we use in vivo imaging to identify a previously undescribed variant of axon damage in a ...
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News and Views by M.J. Craner and L. Fugger

In vivo two-photon imaging of sensory-evoked dendritic calcium signals in cortical neurons
Jia H*, Rochefort NL*, Chen X, Konnerth A. *equal contribution
Nature Protocols
Abstract Neurons in cortical sensory regions receive modality-specific information through synapses that are located on their dendrites. Recently, the use of two-photon microscopy combined with whole-cell recordings has helped to identify visually evoked dendritic calcium signals in mouse visual cor ...
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Tracking stem cell differentiation in the setting of automated optogenetic stimulation
Stroh A, Tsai HC, Ping Wang L, Zhang F, Kressel J, Aravanis A, Santhanam N, Deisseroth K, Konnerth A, Schneider MB.
Stem Cells
Abstract Membrane depolarization has been shown to play an important role in the neural differentiation of stem cells as well as in the survival and function of mature neurons. Here we introduce a microbial opsin into embryonic stem cells and develop optogenetic technology for stem cell engineering ...
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Disruption of the olivo-cerebellar circuit by Purkinje neuron-specific ablation of BK channels
Chen X, Kovalchuk Y, Adelsberger H, Henning HA, Sausbier M, Wietzorrek G, Ruth P, Yarom Y, Konnerth A.
Proc Natl Acad Sci U S A. 2010 Jul 6
Abstract The large-conductance voltage- and calcium-activated potassium (BK) channels are ubiquitously expressed in the brain and play an important role in the regulation of neuronal excitation. Previous work has shown that the total deletion of these channels causes an impaired motor behavior, con ...
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Dendritic organization of sensory input to cortical neurons in vivo
Hongbo Jia*, Nathalie L. Rochefort*, Xiaowei Chen & Arthur Konnerth. *equal contribution
Nature 464, 1307-1312 (29 April 2010)
In sensory cortex regions, neurons are tuned to specific stimulus features. For example, in the visual cortex, many neurons fire predominantly in response to moving objects of a preferred orientation. However, the characteristics of the synaptic input that cortical neurons receive to generate their ...
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News and Views by Priebe NJ, Ferster D.

Cell-type specific properties of pyramidal neurons in neocortex underlying a layout that is modifiable depending on the cortical area
Groh A, Meyer HS, Schmidt EF, Heintz N, Sakmann B, Krieger P.
Cereb Cortex. 2010 Apr;20(4):826-36.
To understand sensory representation in cortex, it is crucial to identify its constituent cellular components based on cell-type-specific criteria. With the identification of cell types, an important question can be addressed: to what degree does the cellular properties of neurons depend on cortical ...
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Rapid time course of action potentials in spines and remote dendrites of mouse visual cortex neurons.
Holthoff K, Zecevic D, Konnerth A.
J Physiol. 2010 Apr 1;588(Pt 7):1085-96.
Axonally initiated action potentials back-propagate into spiny dendrites of central mammalian neurons and thereby regulate plasticity at excitatory synapses on individual spines as well as linear and supralinear integration of synaptic inputs along dendritic branches. Thus, the electrical behaviour ...
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Perspectives by Wu JY, Cohen LB.

Sparsification of neuronal activity in the visual cortex at eye-opening.
Rochefort NL, Garaschuk O, Milos RI, Narushima M, Marandi N, Pichler B, Kovalchuk Y, Konnerth A.
Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):15049-54. Epub 2009 Aug 14.
Eye-opening represents a turning point in the function of the visual cortex. Before eye-opening, the visual cortex is largely devoid of sensory inputs and neuronal activities are generated intrinsically. After eye-opening, the cortex starts to integrate visual information. Here we used in vivo two-p ...
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Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease
Busche MA, Eichhoff G, Adelsberger H, Abramowski D, Wiederhold KH, Haass C, Staufenbiel M, Konnerth A, Garaschuk O.
Science. 2008 Sep 19;321(5896):1686-9.
The neurodegeneration observed in Alzheimer's disease has been associated with synaptic dismantling and progressive decrease in neuronal activity. We tested this hypothesis in vivo by using two-photon Ca2+ imaging in a mouse model of Alzheimer's disease. Although a decrease in neuronal activity was ...
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TRPC3 channels are required for synaptic transmission and motor coordination.
Hartmann J, Dragicevic E, Adelsberger H, Henning HA, Sumser M, Abramowitz J, Blum R, Dietrich A, Freichel M, Flockerzi V, Birnbaumer L, Konnerth A.
Neuron. 2008 Aug 14;59(3):392-8.
In the mammalian central nervous system, slow synaptic excitation involves the activation of metabotropic glutamate receptors (mGluRs). It has been proposed that C1-type transient receptor potential (TRPC1) channels underlie this synaptic excitation, but our analysis of TRPC1-deficient mice does not ...
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Ex vivo imaging of motor axon dynamics in murine triangularis sterni explants
Kerschensteiner M, Reuter MS, Lichtman JW, Misgeld T.
Nat Protoc. 2008;3(10):1645-53.
We provide a protocol that describes an explant system that allows the dynamics of motor axons to be imaged. This method is based on nerve-muscle explants prepared from the triangularis sterni muscle of mice, a thin muscle that covers the inside of the thorax. These explants, which can be maintained ...
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