| Research Focus: Synaptic activation of cerebellar Purkinje cells |
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I use patch clamp recordings in vitro to determine the relative contribution of calcium and potassium channels to synaptic responses in Purkinje cells |
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In vitro slice preparation |
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Below are short summaries of my projects published from the lab. |
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I use patch clamp recording techniques to examine how voltage-gated potassium and calcium-dependent currents shape the firing properties of cerebellar Purkinje cells. The contribution of specific ion channels activated by synaptic inputs are analyzed using direct stimulation of afferent inputs or current commands to simulate the postsynaptic response. |
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In this study we show that climbing fiber input activated at physiological frequencies blocks an intrinsic trimodal pattern inherent to Purkinje cells studied in vitro, restoring tonic Na+ spike discharge similar to that found in vivo. Moreover, all the effects of direct climbing fiber stimulation were reproduced by simulating climbing fiber input with an injected EPSC in the presence of synaptic blockers, emphasizing a key role for the postsynaptic complex spike depolarization in determining Purkinje cell activity. See McKay et al. 2007. |
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We show that a simple firing model undergoing a saddle homoclinic bifurcation can reproduce many of the key properties of Purkinje cells. Each spike is followed by a relatively large depolarizing afterpotential (DAP) that can sustain tonic firing given a brief stimulation from rest. Consequently, within the context of a saddle homoclinic bifurcation the DAP is critical for bistable dynamics and many of the other electrophysiological characteristics of Purkinje cells. PDF |
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A-type potassium channels of the Kv4 family regulate the latency and frequency of spike output in numerous CNS cells. Kv4 channels complex with Potassium Channel Interacting Proteins (KChIPs), a family of calcium sensor proteins that should confer calcium sensitivity. However, neither the physiological source for calcium nor its effects on A-type current were known. Here we show that T-type (Cav3) calcium channels associate with the Kv4 complex to selectively modulate Kv4 inactivation and establish function in a physiological range. See Anderson et al. (2010).
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Here we examined the role for IT and IH in generating the rebound responses that are evoked in deep cerebellar neurons in response to inhibitory input from Purkinje cells. We used recordings in vitro and modeling to find that only a small fraction of the total IT and IH available to a cell are activated by physiological levels of hyperpolarization. However, the currents activted were still sufficient to differentially control the latency, frequency and precision of spike firing during the immediate phase of a rebound response. See Engbers et al. (2011).
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Peer Reviewed Publications
McKay, B.E., Engbers, J.D.T., Mehaffey, W.H., Gordon, G., Molineux, M.L., Bains, J. and Turner, R.W. (2007) Climbing fiber discharge regulates cerebellar functions by controlling the intrinsic characteristics of Purkinje cell output. J. Neurophysiology 97: 2590-2604. PDF
Fernandez, F.R., Engbers, J.D.T. and Turner, R.W. (2007) Firing dynamics of cerebellar Purkinje cells. J. Neurophysiology, 98(1): 278-94. PDF
Anderson, D.M., Mehaffey, W.H., Iftinca, M., Rehak, R., Engbers, J.D.T., Hameed, S., Zamponi, G.W. and Turner, R.W. (2010) Regulation of neuronal activity by Cav3-Kv4 channel signaling complexes. Nature Neuroscience, 13:333-337. Link
Engbers, J.D.T.*, Anderson, D.*, Tadayonnejad, R.*, Mehaffey, W.H., Molineux, M.L. and Turner, R.W. (2011) Distinct roles for IT and IH in controlling the frequency and timing of rebound spike responses. J. Physiology (Lond.), 589 (Pt 22): 5391-413. * Shared first authors. PDF
Haitao Y., Tsutsui, S., Hameed, S., Kannanayakal, T.J., Chen, L., Peng, X. , Engbers, J.D.T., Lipton,S.A., Stys, P. and Zamponi, G.W. (2012) Aβ neurotoxicity depends on interactions between copper ions, prion protein and N-methyl-Daspartate receptors. PNAS, In Press.
Engbers, J.D.T.*, Anderson, D.*, Asmara, H., Rehak, R., Mehaffey, W.H., Hameed, S., McKay, B.E., Kruskic, M., Zamponi, G.W. and Turner, R.W. (2011) Intermediate conductance calcium-activated potassium channels modulate summation of parallel fiber input in cerebellar Purkinje cells. PNAS, In Press. * Shared first authors.
McKay, B.E., Tadayonnejad, R., Anderson, D.M., Engbers, J.D.T., Fernandez, F.R., and Turner, R.W. (2010) Establishing in vivo like activity in rat cerebellar cells maintained in vitro. Isolated Neural Circuits, in Neuromethods (Ballanyi, K., ed.), Springer In Press.
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Engbers, J.D.T. Synaptic inputs are shaped by postsynaptic potassium channels in cerebellar Purkinje cells, Summer Student Symposium, University of Calgary 2006.
McKay, B.E., Engbers, J.D.T., Mehaffey, W.H., Gordon, G.R.J., Molineux, M.L., Bains, J.S. and Turner, R.W. Climbing fibre control of Purkinje cell spike output. Can Assoc Neurosci 2007 [Can J. Neurol. Sci., 34 (Supplement 3): S87].
Anderson, D.M., Mehaffey, W.H., Engbers, J.D.T, Rehak, R., Hamid, S., Zamponi, G.W. and Turner, R.W. T-type mediated calcium influx dynamically modulates Kv4 inactivation. Can. Assoc. Neurosci. Vancouver 2009.
Anderson, D.M., Iftinca, M., Mehaffey, W.H., Rehak, R., Engbers, J.D.T., Hamid, S., Zamponi, G.W. and Turner, R.W. Regulation of neuronal output by Cav3-Kv4 signalling complexes. Proc. Soc. Neurosci. 2009.
Tadayonnejad, R., Engbers, J.D.T., Anderson, D., Mehaffey, W.H. and Turner, R.W. The role of IH and IT in controlling rebound burst properties of Deep Cerebellar Nuclear cells. Can Assoc. Neurosci., 2010.
Tadayonnejad, R., Engbers, J.D.T., Anderson, D., Mehaffey, W.H. and Turner, R.W. IT and IH selectively regulate rate coding and spike precision in deep cerebellar nuclear cells. Proc. Soc. Neurosci., 2010.
Engbers, J.D.T., Anderson, D., Rehak, R., Mehaffey, W.H., McKay, B.E., Zamponi, G.W. and Turner, R.W. T-type/IK channel signalling complex modulates summation of parallel fiber inputs in cerebellar Purkinje cells. Can. Assoc. Neurosci. 2010.
Engbers, J.D.T., Anderson, D., Rehak, R., Mehaffey, W.H., McKay, B.E., Zamponi, G.W. and Turner, R.W. IKCa channels establish a high pass filter for parallel fiber input in cerebellar Purkinje cells. Gordon Conference, Cerebellum in Health and Disease, New London, NH, 2011.
Engbers, J.D.T., Anderson, D., Rehak, R., Asmara, H., Mehaffey, W.H., Hameed, S., McKay, B.E., Kruskic, M., Zamponi, G.W., Turner, R.W. IKCa-Cav3 complex reduces temporal summation of parallel fiber input in cerebellar Purkinje cells. IBRO World Cong. Neuroscience, 2011.
Engbers, J.D.T., Anderson, D., Rehak, R., Mehaffey, W.H., McKay, B.E., Kruskic, M., Zamponi, G.W., Turner, R.W. IKCa-Cav3 complex creates a high pass filter for parallel fiber input in cerebellar Purkinje cells. Comp. Neurosci., 2011. Prize, Student Poster Presentation.
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