| 1. |
- Alkhori, Liza, et al.
(författare)
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Hh signalling regulates odorant receptor cilia localization in Drosophila
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Hedgehog (Hh) signaling is a key regulatory pathway during development. Here, we show that in adult OSNs the Hh pathway regulate ?dorant receptor transport to cilia and put forward a novel non-developmental function of the pathway as a neuromodulator. We demonstrate that the level of Hh signal modulate the OSNs response to odors. We show that knock down of Hh and Smoothened (Smo), a transmembrane protein that transduce the signal, are required for receptor transport. We further show that the coreceptor, Orco, has an Hh independent transport path and that knock down of Smo segregate OR and Orco to different vesicular compartments. Last, we show that the odor response to the second receptor type in Drosophila olfaction, the ionotropic receptors (IRs), also require Hh signalling. Thus, Hh signalling is a general regulator of the odorant response that fulfils the criteria of being a potential player in Drosophila odorant adaptation.
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| 2. |
- Granseth, Björn, 1973-, et al.
(författare)
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Regulation of thalamocortical axon branching by BDNF and synaptic vesicle cycling
- 2013
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Ingår i: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 7:202
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Tidskriftsartikel (refereegranskat)abstract
- During development, axons form branches in response to extracellular molecules. Little is known about the underlying molecular mechanisms. Here, we investigate how neurotrophin-induced axon branching is related to synaptic vesicle cycling for thalamocortical axons. The exogenous application of brain-derived neurotrophic factor (BDNF) markedly increased axon branching in thalamocortical co-cultures, while removal of endogenous BDNF reduced branching. Over-expression of a C-terminal fragment of AP180 that inhibits clathrin-mediated endocytosis affected the laminar distribution and the number of branch points. A dominant-negative synaptotagmin mutant that selectively targets synaptic vesicle cycling, strongly suppressed axon branching. Moreover, axons expressing the mutant synaptotagmin were resistant to the branch-promoting effect of BDNF. These results suggest that synaptic vesicle cycling might regulate BDNF induced branching during the development of the axonal arbor.
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| 3. |
- Nath, Sangeeta, et al.
(författare)
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Spreading of Neurodegenerative Pathology via Neuron-to-Neuron Transmission of beta-Amyloid
- 2012
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Ingår i: Journal of Neuroscience. - : SOC NEUROSCIENCE. - 0270-6474 .- 1529-2401. ; 32:26, s. 8767-8777
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimers disease (AD) is the major cause of dementia. During the development of AD, neurofibrillary tangles progress in a fixed pattern, starting in the transentorhinal cortex followed by the hippocampus and cortical areas. In contrast, the deposition of beta-amyloid (A beta) plaques, which are the other histological hallmark of AD, does not follow the same strict spatiotemporal pattern, and it correlates poorly with cognitive decline. Instead, soluble A beta oligomers have received increasing attention as probable inducers of pathogenesis. In this study, we use microinjections into electrophysiologically defined primary hippocampal rat neurons to demonstrate the direct neuron-to-neuron transfer of soluble oligomeric A beta. Additional studies conducted in a human donor-acceptor cell model show that this A beta transfer depends on direct cellular connections. As the transferred oligomers accumulate, acceptor cells gradually show beading of tubulin, a sign of neurite damage, and gradual endosomal leakage, a sign of cytotoxicity. These observations support that intracellular A beta oligomers play a role in neurodegeneration, and they explain the manner in which A beta can drive disease progression, even if the extracellular plaque load is poorly correlated with the degree of cognitive decline. Understanding this phenomenon sheds light on the pathophysiological mechanism of AD progression. Additional elucidation will help uncover the detailed mechanisms responsible for the manner in which AD progresses via anatomical connections and will facilitate the development of new strategies for stopping the progression of this incapacitating disease.
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| 4. |
- Nersisyan, Syune, et al.
(författare)
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Cholinergic modulation of synaptic properties of cortical layer VI input to posteromedial thalamic nucleus of the rat investigated in vitro
- 2012
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Ingår i: Acta Neurobiologiae Experimentalis. - 0065-1400 .- 1689-0035. ; 72:4, s. 461-467
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Tidskriftsartikel (refereegranskat)abstract
- The second order somatosensory thalamic nucleus (posteromedial nucleus, PoM) receives excitatory projection from layer VI of somatosensory cortex. While it is known that layer VI cortical input to first order, ventrobasal nucleus (VB) is modulated by cholinergic projections from the brainstem, no such data exists concerning the PoM nucleus. In order to study if layer VI corticothalamic transmission to PoM is also modulated we used patch-clamp recording in thalamocortical slices from the rat's brain. Excitatory postsynaptic potentials (EPSPs) were evoked in PoM cells by trains of 5 electrical pulses at 20 Hz frequency applied to corticothalamic fibers. After carbachol was applied to mimic activation of the cholinergic neuromodulatory system corticothalamic EPSP amplitudes were reduced, while facilitation of EPSP amplitudes was enhanced for each next pulse in the series. Such cholinergic control of layer VI corticothalamic synapses in PoM may be used as gain modulator for the transfer of the peripheral sensory information to the cortex.
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