4 YEAR PhD IN NEUROSCIENCE
Institute of Neurology
CNS synaptic transmission, epilepsy, and inherited mutations of ion channels in neurological disease
We study use-dependent plasticity and modulation of
synaptic, neuronal and circuit function in the brain, and ion channel
dysfunction in epilepsy and other paroxysmal neurological diseases.
Much of our work relies on electrophysiological and pharmacological methods in acute hippocampal slices. We also apply confocal and multi-photon imaging of Ca2+ signals in subcellular structures such as axonal varicosities and dendritic spines, in order to understand the mechanisms of modulation of synaptic transmission. We have recently uncovered two forms of long-term potentiation (LTP) of excitatory signalling in hippocampal interneurons. LTP in the inhibitory circuit has extensive implications for the interface between network computations and memory encoding.
We have addressed the mechanisms of several inherited paroxysmal neurological diseases caused by ion channel mutations. These include disorders related to the voltage-gated K+ channel Kv1.1, the P/Q-type Ca2+ channel CaV2.1, several muscle ion channels (Kir2.1, CaV1.1, NaV1.4 and ClC-1), and the a1 glycine receptor subunit. This work has relied on heterologous expression of ion channels, some of which have been labelled with fluorescent proteins, and we have recently extended this to lentivirus-mediated expression in neuronal cultures. We are also looking at knock-in mouse models of familial hemiplegic migraine and episodic ataxia using in vitro electrophysiology, Ca2+ imaging and FM dyes.
Lentiviral expression of mutant K+ channels in neuronal culture
Nicotinic receptor-mediated modulation of GABAA receptors
Kullmann DM and Schorge S (2008)
Voltage-gated ion channels: molecular biology and role of mutations in epilepsy.
In: Epilepsy: A Comprehensive Textbook. Second Edition. Eds: J Engel, T Pedley. LWW. pp: 253-265
Kullmann DM, Lamsa KP (2008)
Roles of distinct glutamate receptors in induction of anti-Hebbian long-term potentiation.
J Physiol. 586:1481-6
Sylantyev S, Savtchenko LP, Niu Y-P, Ivanov AI, Jensen TP, Kullmann DM, Xiao M-Y, Rusakov DA (2008)
Electric fields due to synaptic currents sharpen excitatory transmission.
Kullmann DM, Lamsa KP (2007)
Long-term synaptic plasticity in hippocampal interneurons.
Nat Rev Neurosci. 8:687-99
Wanaverbecq N, Semyanov A, Pavlov I, Walker MC, Kullmann DM (2007)
Cholinergic axons modulate GABAergic signaling among hippocampal interneurons via postsynaptic α7 nicotinic receptors.
J Neurosci 27, 5683-5693
Lamsa KP, Heeroma JH, Somogyi P, Rusakov DA, Kullmann (2007)
Anti-Hebbian long-term potentiation in the hippocampal feed-back inhibitory circuit.
Science 315, 1262 – 1266
Volynski K, Rusakov DA, Kullmann DM (2006)
Presynaptic fluctuations and release-independent depression.
Nature Neurosci 9:1091-93
Scimemi A, Semyanov A, Sperk G, Kullmann DM, Walker MC (2005)
Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus.
J. Neurosci. 25:10016-24