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Séminaire impromptu - Leonie Pothmann ‘Changes of inhibitory micronetworks in the epileptic hippocampus and their response to anticonvulsant drugs’

Abstract :


CA1 microcircuits show profound reorganization in human and experimental temporal lobe epilepsy due to synaptic sprouting, loss of certain neuron types, and functional synaptic changes.
The divers tasks of interneurons suggest, however, that morphological and behavioral alterations of surviving interneurons will also strongly influence network activity. The temporal activity pattern of a given interneuron is shaped by its synaptic inputs as well as its intrinsic properties. The spatial component of inhibition is determined by the axon morphology of different interneuron classes. Within CA1, a major source of excitatory input of interneurons is provided by local CA1 pyramidal cells, thereby creating a feedback inhibitory loop. We investigated whether the spatio-temporal profile of feedback inhibition in CA1 is changed in experimental epilepsy.

 In the second part of my talk I will present data describing the effects of anticonvulsant drugs on the functioning of inhibitory microcircuits. The mechanisms of action of many CNS drugs have been studied extensively at the level of their target proteins, but the effects of these compounds at the level of complex CNS networks composed of different types of excitatory and inhibitory neurons are not well understood. Many currently used anticonvulsant drugs are known to exert potent use-dependent blocking effects on voltage-gated Na+ channels, thereby inhibiting pathological high-frequency firing. However, some GABAergic inhibitory neurons are capable of firing at very high rates, suggesting that these anticonvulsants should cause impaired GABAergic inhibition. We therefore studied the effects of different sodium channel blocking anticonvulsants on GABAergic inhibitory micro-networks in the rodent hippocampus of control and epileptic animals.

Selected publications

  • Function of inhibitory micronetworks is spared by Na+ channel-acting anticonvulsant drugs.Pothmann L, Müller C, Averkin RG, Bellistri E, Miklitz C, Uebachs M, Remy S, Menendez de la Prida L, Beck H. J Neurosci. 2014 Jul 16;34(29):9720-35. doi: 10.1523/JNEUROSCI.2395-13.2014.
     
  • Impaired D-serine-mediated cotransmission mediates cognitive dysfunction in epilepsy.Klatte K, Kirschstein T, Otte D, Pothmann L, Müller L, Tokay T, Kober M, Uebachs M, Zimmer A, Beck H. J Neurosci. 2013 Aug 7;33(32):13066-80. doi: 10.1523/JNEUROSCI.5423-12.2013. 
  • Two modes of information processing in the electrosensory system of the paddlefish (Polyodon spathula). Pothmann L, Wilkens LA, Hofmann MH. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2012 Jan;198(1):1-10. doi: 10.1007/s00359-011-0681-2. Epub 2011 Sep 30.