Medical Research Council Anatomical Neuropharmacology Unit

Oxford, United Kingdom

Medical Research Council Anatomical Neuropharmacology Unit

Oxford, United Kingdom
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Koshimizu Y.,Kyoto University | Koshimizu Y.,Japan Science and Technology Agency | Koshimizu Y.,Doshisha University | Fujiyama F.,Kyoto University | And 5 more authors.
Journal of Comparative Neurology | Year: 2013

The subthalamic nucleus (STN) of the basal ganglia plays a key role in motor control, and STN efferents are known to mainly target the external segment of the globus pallidus (GPe), entopeduncular nucleus (Ep), and substantia nigra (SN) with some axon collaterals to the other regions. However, it remains to be clarified how each STN neuron projects axon fibers and collaterals to those target nuclei of the STN. Here we visualized the whole axonal arborization of single STN neurons in the rat brain by using a viral vector expressing membrane-targeted green fluorescent protein, and examined the distribution of axon boutons in those target nuclei. The vast majority (8-9) of 10 reconstructed STN neurons projected to the GPe, SN, caudate-putamen (CPu), and Ep, which received, on average ± SD, 457 ± 425, 400 ± 347, 126 ± 143, and 106 ± 100 axon boutons per STN neuron, respectively. Furthermore, the density of axon boutons in the GPe was highest among these nuclei. Although these target nuclei were divided into calbindin-rich and -poor portions, STN projection showed no exclusive preference for those portions. Since STN neurons mainly projected not only to the GPe, SN, and Ep but also to the CPu, the subthalamostriatal projection might serve as a positive feedback path for the striato-GPe-subthalamic disinhibitory pathway, or work as another route of cortical inputs to the striatum through the corticosubthalamostriatal disynaptic excitatory pathway. © 2012 Wiley Periodicals, Inc.


Karayannis T.,Medical Research Council Anatomical Neuropharmacology Unit | Karayannis T.,New York University | Elfant D.,Medical Research Council Anatomical Neuropharmacology Unit | Huerta-Ocampo I.,Medical Research Council Anatomical Neuropharmacology Unit | And 5 more authors.
Journal of Neuroscience | Year: 2010

The kinetics of GABAergic synaptic currents can vary by an order of magnitude depending on the cell type. The neurogliaform cell (NGFC) has recently been identified as a key generator of slow GABAA receptor-mediated volume transmission in the isocortex. However, the mechanisms underlying slow GABAA receptor-mediated IPSCs and their use-dependent plasticity remain unknown. Here, we provide experimental and modeling data showing that hippocampal NGFCs generate an unusually prolonged (tens of milliseconds) but lowconcentration (micromolar range) GABA transient, which is responsible for the slow response kinetics and which leads to a robust desensitization of postsynaptic GABAA receptors. This strongly contributes to the use-dependent synaptic depression elicited by various patterns of NGFC activity including the one detected during theta network oscillations in vivo. Synaptic depression mediated by NGFCs is likely to play an important modulatory role in the feedforward inhibition of CA1 pyramidal cells provided by the entorhinal cortex. Copyright © 2010 the authors.


Murray Sherman S.,University of Chicago | Guillery R.W.,Medical Research Council Anatomical Neuropharmacology Unit
Journal of Neurophysiology | Year: 2011

Essentially all cortical areas receive thalamic inputs and send outputs to lower motor centers. Cortical areas communicate with each other by means of direct corticocortical and corticothalamocortical pathways, often organized in parallel. We distinguish these functionally, stressing that the transthalamic pathways are class 1 (formerly known as "driver") pathways capable of transmitting information, whereas the direct pathways vary, being either class 2 (formerly known as "modulator") or class 1. The transthalamic pathways provide a thalamic gate that can be open or closed (and otherwise more subtly modulated), and these inputs to the thalamus are generally branches of axons with motor functions. Thus the transthalamic corticocortical pathways that can be gated carry information about the cortical processing in one cortical area and also about the motor instructions currently being issued from that area and copied to other cortical areas. © 2011 the American Physiological Society.


Perestenko P.V.,Medical Research Council Anatomical Neuropharmacology Unit | Pooler A.M.,Medical Research Council Anatomical Neuropharmacology Unit | Pooler A.M.,Institute of Psychiatry | Noorbakhshnia M.,Medical Research Council Anatomical Neuropharmacology Unit | And 5 more authors.
FEBS Journal | Year: 2010

The copines are a family of C2- and von Willebrand factor A-domain-containing proteins that have been proposed to respond to increases in intracellular calcium by translocating to the plasma membrane. The copines have been reported to interact with a range of cell signalling and cytoskeletal proteins, which may therefore be targeted to the membrane following increases in cellular calcium. However, neither the function of the copines, nor their actual movement to the plasma membrane, has been fully established in mammalian cells. Here, we show that copines-1, -2, -3, -6 and -7 respond differently to a methacholine-evoked intracellular increase in calcium in human embryonic kidney cell line-293 cells, and that their membrane association requires different levels of intracellular calcium. We demonstrate that two of these copines associate with different intracellular vesicles following calcium entry into cells, and identify a novel conserved amino acid sequence that is required for their membrane translocation in living cells. Our data show that the von Willebrand factor A-domain of the copines modulates their calcium sensitivity and intracellular targeting. Together, these findings suggest a different set of roles for the members of this protein family in mediating calcium-dependent processes in mammalian cells. © 2010 FEBS.


PubMed | Medical Research Council Anatomical Neuropharmacology Unit
Type: Journal Article | Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience | Year: 2010

The kinetics of GABAergic synaptic currents can vary by an order of magnitude depending on the cell type. The neurogliaform cell (NGFC) has recently been identified as a key generator of slow GABA(A) receptor-mediated volume transmission in the isocortex. However, the mechanisms underlying slow GABA(A) receptor-mediated IPSCs and their use-dependent plasticity remain unknown. Here, we provide experimental and modeling data showing that hippocampal NGFCs generate an unusually prolonged (tens of milliseconds) but low-concentration (micromolar range) GABA transient, which is responsible for the slow response kinetics and which leads to a robust desensitization of postsynaptic GABA(A) receptors. This strongly contributes to the use-dependent synaptic depression elicited by various patterns of NGFC activity including the one detected during theta network oscillations in vivo. Synaptic depression mediated by NGFCs is likely to play an important modulatory role in the feedforward inhibition of CA1 pyramidal cells provided by the entorhinal cortex.


PubMed | Medical Research Council Anatomical Neuropharmacology Unit
Type: Journal Article | Journal: The FEBS journal | Year: 2010

The copines are a family of C2- and von Willebrand factor A-domain-containing proteins that have been proposed to respond to increases in intracellular calcium by translocating to the plasma membrane. The copines have been reported to interact with a range of cell signalling and cytoskeletal proteins, which may therefore be targeted to the membrane following increases in cellular calcium. However, neither the function of the copines, nor their actual movement to the plasma membrane, has been fully established in mammalian cells. Here, we show that copines-1, -2, -3, -6 and -7 respond differently to a methacholine-evoked intracellular increase in calcium in human embryonic kidney cell line-293 cells, and that their membrane association requires different levels of intracellular calcium. We demonstrate that two of these copines associate with different intracellular vesicles following calcium entry into cells, and identify a novel conserved amino acid sequence that is required for their membrane translocation in living cells. Our data show that the von Willebrand factor A-domain of the copines modulates their calcium sensitivity and intracellular targeting. Together, these findings suggest a different set of roles for the members of this protein family in mediating calcium-dependent processes in mammalian cells.

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