| 51. |
- Westin, Linda, et al.
(författare)
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Nanoscopic spine localization of Norbin, an mGluR5 accessory protein
- 2014
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Ingår i: BMC Neuroscience. - : BioMed Central. - 1471-2202. ; 15, s. 45-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Norbin is a neuron-specific, cytosolic protein that interacts with the metabotropic glutamate receptor 5 (mGluR5) and has a profound impact on mGluR5 signaling. Yet, little is known about its synaptic distribution. Results: Here we have analyzed the spatial relationship between Norbin, postsynaptic density protein 95 (PSD-95), actin and mGluR5 in spines using super-resolution microscopy. Norbin was found to have a high degree of colocalization with actin and a lower degree of colocalization with PSD-95. Co-immunoprecipitation studies confirmed that interaction occurs between Norbin and actin, but not between Norbin and PSD-95. Norbin was also found to have a high degree of colocalization with the perisynaptically located mGluR5. Findings based on structured illumination microscopy (3D-SIM) of exogenous expressed Norbin-GFP were confirmed by stimulated emission depletion microscopy (STED) of immunolabeled endogenous Norbin. Conclusions: Norbin associates with actin rather than with PSD-95 in dendritic spines. Results regarding protein localization and colocalization performed with conventional confocal microscopy must be interpreted with great caution. The now available super-resolution microscopy techniques provide more accurate information about sub-cellular protein localization than previously was possible.
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| 52. |
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| 53. |
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| 54. |
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| 55. |
- Nässel, Dick, et al.
(författare)
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A large population of diverse neurons in the Drosophila central nervous system expresses short neuropeptide F, suggesting multiple distributed peptide functions
- 2008
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Ingår i: BMC Neuroscience. - : Biomed Central. - 1471-2202. ; 9:1, s. 90-125
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Tidskriftsartikel (refereegranskat)abstract
- Background Insect neuropeptides are distributed in stereotypic sets of neurons that commonly constitute a small fraction of the total number of neurons. However, some neuropeptide genes are expressed in larger numbers of neurons of diverse types suggesting that they are involved in a greater diversity of functions. One of these widely expressed genes, snpf, encodes the precursor of short neuropeptide F (sNPF). To unravel possible functional diversity we have mapped the distribution of transcript of the snpf gene and its peptide products in the central nervous system (CNS) of Drosophila in relation to other neuronal markers. Results There are several hundreds of neurons in the larval CNS and several thousands in the adult Drosophila brain expressing snpf transcript and sNPF peptide. Most of these neurons are intrinsic interneurons of the mushroom bodies. Additionally, sNPF is expressed in numerous small interneurons of the CNS, olfactory receptor neurons (ORNs) of the antennae, and in a small set of possibly neurosecretory cells innervating the corpora cardiaca and aorta. A sNPF-Gal4 line confirms most of the expression pattern. None of the sNPF immunoreactive neurons co-express a marker for the transcription factor DIMMED, suggesting that the majority are not neurosecretory cells or large interneurons involved in episodic bulk transmission. Instead a portion of the sNPF producing neurons co-express markers for classical neurotransmitters such as acetylcholine, GABA and glutamate, suggesting that sNPF is a co-transmitter or local neuromodulator in ORNs and many interneurons. Interestingly, sNPF is coexpressed both with presumed excitatory and inhibitory neurotransmitters. A few sNPF expressing neurons in the brain colocalize the peptide corazonin and a pair of dorsal neurons in the first abdominal neuromere coexpresses sNPF and insulin-like peptide 7 (ILP7). Conclusion It is likely that sNPF has multiple functions as neurohormone as well as local neuromodulator/co-transmitter in various CNS circuits, including olfactory circuits both at the level of the first synapse and at the mushroom body output level. Some of the sNPF immunoreactive axons terminate in close proximity to neurosecretory cells producing ILPs and adipokinetic hormone, indicating that sNPF also might regulate hormone production or release.
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| 56. |
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| 57. |
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| 58. |
- Brasselet, R, et al.
(författare)
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Fast encoding/decoding of haptic microneurography data based on first spike latencies
- 2009
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Ingår i: BMC Neuroscience. - 1471-2202. ; 10:1, s. 349-350
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- During haptic exploration tasks, forces are applied to the fingertips, which constitute the most sensitive parts of the hand and are prominently involved in object manipulation/ recognition tasks. The epidermis is innervated with thousands of sensory cells, called mechanoreceptors, that encode the mechanical indentations and deformations of the skin. These cells project directly to a dorsal column nucleus called the cuneate nucleus (CN) that constitutes the first synaptic relay to the central nervous system. Recent microneurography studies in humans [1] suggest that the relative timing of impulses from ensembles of mechanoreceptor afferents can convey information about important contact parameters faster than the fastest possible rate code and are fast enough to account for the use of tactile signals in natural manipulation. Here, we study a biologically plausible encoding/decoding process accounting for the relative spike timing of the signals propagating from peripheral nerve fibres onto second- order CN neurons. The CN is modelled as a population of 450 spiking neurons receiving as inputs the spatiotemporal responses of real mechanoreceptors obtained via microneurography recordings in humans. An information-theoretic approach is used to quantify the efficiency of the haptic discrimination process. To this extent, a novel entropy definition has been derived analytically. This measure proved to be a promising decoding scheme to generalize the classical Shannon's entropy for spiking neural codes, and it allowed us to compute mutual information (MI) in the presence of a large output space (i.e., 450 CN spike train responses) with a 1 ms temporal precision. Using a plasticity rule designed to maximise information transfer explicitly [2], a complete discrimination of 81 distinct stimuli occurred already within 40 ms after the first afferent spike, whereas a partial discrimination (80% of the maximum MI) was possible as rapidly as 20 ms. The rationale behind this study was to corroborate our working hypothesis that the CN does not constitute a mere synaptic relay, but it rather conveys an optimal contextual account (in terms of both fast and reliable information transfer) of peripheral tactile inputs to downstream structures (in particular to the thalamus and the cerebellum). Therefore, the CN may play a relevant role in the early processing of haptic information and it would constitute an important component of the haptic classification process (e.g., by facilitating fast discrimination of haptic contexts, minimising destructive interference over lifelong learning, and maximising memorycapacity).
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| 59. |
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| 60. |
- Klaus, A., et al.
(författare)
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The influence of subthreshold membrane potential oscillations and GABAergic input on firing activity in striatal fast-spiking neurons
- 2009
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Ingår i: BMC Neuroscience. - 1471-2202. ; 10:Suppl.1, s. P244-
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Tidskriftsartikel (refereegranskat)abstract
- The striatum is the main input stage of the basal ganglia system, which is involved in executive functions of the forebrain, such as the planning and the selection of motor behavior. Feedforward inhibition of medium-sized spiny projection neurons in the striatum by fast-spiking interneurons is supposed to be an important determinant of controlling striatal output to later stages of the basal ganglia[1]. Striatal fast-spiking interneurons, which constitute approximately 1–2% of all striatal neurons, show many similarities to cortical fast-spiking cells. In response to somatic current injection, for example, some of these neurons exhibit spike bursts with a variable number of action potentials (so called stuttering)[2-4]. Interestingly, the membrane potential between such stuttering episodes oscillates in the range of 20–100 Hz[3,5]. The first spike of each stuttering episode invariably occurs at a peak of the underlying subthreshold oscillation. In both cortex and striatum, fast-spiking cells are inter-connected by gap junctions[6,7]. In vitro measurements as well as theoretical studies indicate that electrical coupling via gap junctions might be able to promote synchronous activity among these neurons[6,8]. Here we investigate the possible role of subthreshold oscillations on the synchronization of sub- and suprathreshold activity in a model of electrically coupled fast-spiking neurons. We use the model of Golomb et al.[3], which we extended with a dendritic tree so as to be able to simulate distal synaptic input. We show that gap junctions are able to synchronize subthreshold membrane potential fluctuations in response to somatic current injection. However, the oscillations are only prevalent in the subthreshold range and therefore require enough membrane potential depolarization[5]. In response to synaptic input, our model neuron only enters the subthreshold oscillatory regime with AMPA and NMDA synapses located at distal dendrites. Proximal synaptic input leads to more random fluctuations of the membrane potential, reflecting a smaller extent of dendritic filtering of the Poisson-distributed postsynaptic potentials. We furthermore investigate the effect of GABAergic (i.e. inhibitory) input to the model of the fast-spiking neuron and predict that inhibitory input is able to induce a stuttering episode in these cells. We finally discuss our results in the context of the feedforward inhibitory network, which is likely to play an important role in striatal and basal ganglia function.
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