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Regulation of synaptic transmissionThe goal of research in our laboratory is to understand signal transmission in the nervous system with particular emphasis on mechanisms that control synaptic transmission under normal and pathological conditions. Two projects at present involve electrophysiological recordings from neurons of the hippocampus. an area critically involved in learning and memory. One project is focused on the properties of neuronal voltage-gated calcium channels; the other is on rapid modulation of synaptic strength by neurotrophins. Neuronal voltage-gated calcium channels provide a pathway for calcium influx that is required for processes ranging form intracellular signaling to alterations in cellular excitability. In hippocampal neurons. we have found that a subtype of dihydrophridine-sensitive calcium channel shows multiple kinds of voltage-dependent potentiation of its activity. One type of potentiation appears to be unique to central neurons; it has a low threshold and survives transient hyperpolarization. A second type is elicited by much higher voltages and is selectively deactivated at hyperpolarized voltages. Thus. as with synaptic transmission. calcium channel plasticity in the hippocampus has a variety of forms distinguished by their stimulus requirements and duration. Neurotrophins are important regulators of the survival. development. and differentiation of multiple neuronal populations. These effects generally occur over the course of hours. or even days. Recently. evidence has accumulated that neurotrophins can also modulate synaptic transmission. In the hippocampus. we have found that brain-derived neurotrophic factor (BDNF) rapidly and reversibly enhances the strength of synaptic connections. Both the amplitude and the frequency of excitatory post-synaptic currents are increased within two to three minutes of neurotrophin application. Moreover. the potentiation of synaptic current amplitude occurs via a novel post-synaptic mechanism in which BDNF increases the responsiveness to excitatory input. These results suggest a central role for this neurotrophin in the modulation of synaptic transmission in the hippocampus. Selected PublicationsLiu A, Han YR, Li J, Sun D, Ouyang M, Plummer MR, Casaccia-Bonnefil P. (2007) The glial or neuronal fate choice of oligodendrocyte progenitors is modulated by their ability to acquire an epigenetic memory. J Neurosci. 27(27):7339-43. Cortés RY, Arévalo JC, Magby JP, Chao MV, Plummer MR. (2007) Developmental and activity-dependent regulation of ARMS/Kidins220 in cultured rat hippocampal neurons. Dev Neurobiol. 67(13):1687-98. Magby JP, Bi C, Chen ZY, Lee FS, Plummer MR. (2006) Single-cell characterization of retrograde signaling by brain-derived neurotrophic factor. J Neurosci. 26(52):13531-6. Xu F, Plummer MR, Len GW, Nakazawa T, Yamamoto T, Black IB, Wu K. (2006) Brain-derived neurotrophic factor rapidly increases NMDA receptor channel activity through Fyn-mediated phosphorylation. Brain Res. 1121(1):22-34. Gruen ML, Saraswathi V, Nuotio-Antar AM, Plummer MR, Coenen KR, Hasty AH. (2006) Plasma insulin levels predict atherosclerotic lesion burden in obese hyperlipidemic mice. Gruen ML, Plummer MR, Zhang W, Posey KA, Linton MF, Fazio S, Hasty AH. (2005) Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I. J Lipid Res. 46(9):2007-14. Hasty AH. Plummer MR. Weisgraber KH. Linton MF. Fazio S. Swift LL. (2005) The recycling of apolipoprotein E in macrophages: influence of HDL and apolipoprotein A-I. J Lipid Res. 46(7):1433-9. Alder J. Thakker-Varia S. Crozier RA. Shaheen A. Plummer MR. Black IB. (2005) Early presynaptic and late postsynaptic components contribute independently to brain-derived neurotrophic factor-induced synaptic plasticity. J Neurosci. 25(12):3080-5. Alder J. Thakker-Varia S. Bangasser DA. Kuroiwa M. Plummer MR. Shors TJ. Black IB. (2003) Brain-derived neurotrophic factor-induced gene expression reveals novel actions of VGF in hippocampal synaptic plasticity. J Neurosci. 23(34):10800-8. Schjott JM. Hsu SC. Plummer MR. (2003) The neuronal beta 4 subunit increases the unitary conductance of L-type voltage-gated calcium channels in PC12 cells. J Biol Chem. 78(36):33936-42. Thakker-Varia S. Alder J. Crozier RA. Plummer MR. Black IB. (2001) Rab3A is required for brain-derived neurotrophic factor-induced synaptic plasticity: transcriptional analysis at the population and single-cell levels. J Neurosci. 21(17):6782-90. Errico. M.. Crozier. R.A.. Plummer. M.R. & Cowen. D.S. (2001). 5-HT7 receptors activate the MAP kinase ERK in cultured hippocampal neurons. Neuroscience 102: 361-367. Schjöött. J.M. & Plummer. M.R. (2000). Sustained activation of hippocampal Lp-type voltage-gated calcium channels by tetanic stimulation. J. Neurosci. 20: 4786-4797.
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