3 results on '"Wolfgang Kelsch"'
Search Results
2. Genetically Increased Cell-Intrinsic Excitability Enhances Neuronal Integration into Adult Brain Circuits
- Author
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Alice Ainsworth, Carlos Lois, Shuyin Sim, Masayoshi Okada, Wolfgang Kelsch, and Chia-Wei Lin
- Subjects
Patch-Clamp Techniques ,Cell Survival ,Nerve net ,Neuroscience(all) ,Action Potentials ,DEVBIO ,Sensory system ,Biology ,Receptors, N-Methyl-D-Aspartate ,Sodium Channels ,Article ,MOLNEURO ,Mice ,medicine ,Animals ,Premovement neuronal activity ,Patch clamp ,Potassium Channels, Inwardly Rectifying ,Mice, Knockout ,Neurons ,General Neuroscience ,Sodium channel ,Depolarization ,Olfactory Bulb ,Potassium channel ,Rats ,Olfactory bulb ,medicine.anatomical_structure ,nervous system ,CELLBIO ,Nerve Net ,Neuroscience - Abstract
SummaryNew neurons are added to the adult brain throughout life, but only half ultimately integrate into existing circuits. Sensory experience is an important regulator of the selection of new neurons but it remains unknown whether experience provides specific patterns of synaptic input or simply a minimum level of overall membrane depolarization critical for integration. To investigate this issue, we genetically modified intrinsic electrical properties of adult-generated neurons in the mammalian olfactory bulb. First, we observed that suppressing levels of cell-intrinsic neuronal activity via expression of ESKir2.1 potassium channels decreases, whereas enhancing activity via expression of NaChBac sodium channels increases survival of new neurons. Neither of these modulations affects synaptic formation. Furthermore, even when neurons are induced to fire dramatically altered patterns of action potentials, increased levels of cell-intrinsic activity completely blocks cell death triggered by NMDA receptor deletion. These findings demonstrate that overall levels of cell-intrinsic activity govern survival of new neurons and precise firing patterns are not essential for neuronal integration into existing brain circuits.
- Published
- 2010
3. Subcellular localization of type 1 cannabinoid receptors in the rat basal ganglia
- Author
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Ken Mackie, Tamás F. Freund, Ferenc Mátyás, Wolfgang Kelsch, Y. Yanovsky, and Ulrich Misgeld
- Subjects
Male ,Patch-Clamp Techniques ,Morpholines ,Presynaptic Terminals ,Action Potentials ,Substantia nigra ,Naphthalenes ,Biology ,Nucleus accumbens ,Medium spiny neuron ,Basal Ganglia ,Animals, Genetically Modified ,Mice ,Organ Culture Techniques ,Microscopy, Electron, Transmission ,Piperidines ,Receptor, Cannabinoid, CB1 ,Postsynaptic potential ,Cannabinoid Receptor Modulators ,Basal ganglia ,medicine ,Animals ,Rats, Wistar ,Axon ,Long-term depression ,gamma-Aminobutyric Acid ,musculoskeletal, neural, and ocular physiology ,General Neuroscience ,Calcium Channel Blockers ,Immunohistochemistry ,Benzoxazines ,Rats ,Cell biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Globus pallidus ,nervous system ,Pyrazoles ,lipids (amino acids, peptides, and proteins) ,Neuroscience ,psychological phenomena and processes - Abstract
Endocannabinoids, acting via type 1 cannabinoid receptors (CB1), are known to be involved in short-term synaptic plasticity via retrograde signaling. Strong depolarization of the postsynaptic neurons is followed by the endocannabinoid-mediated activation of presynaptic CB1 receptors, which suppresses GABA and/or glutamate release. This phenomenon is termed depolarization-induced suppression of inhibition (DSI) or excitation (DSE), respectively. Although both phenomena have been reported to be present in the basal ganglia, the anatomical substrate for these actions has not been clearly identified. Here we investigate the high-resolution subcellular localization of CB1 receptors in the nucleus accumbens, striatum, globus pallidus and substantia nigra, as well as in the internal capsule, where the striato-nigral and pallido-nigral pathways are located. In all examined nuclei of the basal ganglia, we found that CB1 receptors were located on the membrane of axon terminals and preterminal axons. Electron microscopic examination revealed that the majority of these axon terminals were GABAergic, giving rise to mostly symmetrical synapses. Interestingly, preterminal axons showed far more intense staining for CB1, especially in the globus pallidus and substantia nigra, whereas their terminals were only faintly stained. Non-varicose, thin unmyelinated fibers in the internal capsule also showed strong CB1-labeling, and were embedded in bundles of myelinated CB1-negative axons. The majority of CB1 receptors labeled by immunogold particles were located in the axonal plasma membrane (92.3%), apparently capable of signaling cannabinoid actions. CB1 receptors in this location cannot directly modulate transmitter release, because the release sites are several hundred micrometers away. Interestingly, both the CB1 agonist, WIN55,212-2, as well as its antagonist, AM251, were able to block action potential generation, but via a CB1 independent mechanism, since the effects remained intact in CB1 knockout animals. Thus, our electrophysiological data suggest that these receptors are unable to influence action potential propagation, thus they may not be functional at these sites, but are likely being transported to the terminal fields. The present data are consistent with a role of endocannabinoids in the control of GABA, but not glutamate, release in the basal ganglia via presynaptic CB1 receptors, but also call the attention to possible non-CB1-mediated effects of widely used cannabinoid ligands on action potential generation.
- Published
- 2006
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