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Abdel El Manira, Ph.D.

Abdel El Manira

El Manira Group

Research Focus

Our research aims at understanding the role of intrinsic modulation operating within the spinal networks in producing the locomotor movements. In these studies we use two experimental models (lamprey and zebrafish) whose CNS has the basic features of the vertebrate nervous system and yet orders of magnitude fewer neurons than mammals. We use electrophysiological, imaging and morphological techniques to examine the changes in the activity of individual neurons, their synaptic interactions and the global activity of the spinal locomotor network responsible for locomotion. The set of issues we are addressing include (1) how does the intrinsic activation specific modulatory receptors (mGluRs) regulate the homeostasis of the locomotor network excitability by determining the set-point of the baseline frequency, (2) the mechanisms of short- and long-term plasticity of the locomotor network and (3) the role of retrograde signaling by endocannabinoids in shaping synaptic interactions within the locomotor network and the final locomotor pattern.

By elucidating the mechanisms of the intrinsic glutamatergic modulation underlying the short- and long-term plasticity of the locomotor activity, we will contribute to the design of novel therapeutic methods aiming at potentiating the glutamatergic transmission that can awaken a dormant spinal locomotor network and thus restore function after injury.

The levels of investigation using computational models range from simulations of large scale neural networks, using both biophysically detailed but also more abstract neuron models, down to kinetic models of subcellular processes (e.g. dopamine induced cascades). The latter approach is important for understanding mechanisms involved in e.g. synaptic plasticity and learning. Also we have used biochemical level models to analyse and optimize industrial DNA sequencing methods, as well as to increase the understanding of insulin-secretion coupling in insulin producing beta cells, some projects of which have been collaborations with the industry.

Selected Publications

Andäng M, Hjerling-Leffler J, Moliner A, Lundgren TK, Castelo-Branco G, Nanou E, Pozas E, Bryja V, Halliez S, Nishimaru H, Wilbertz J, Arenas E, Koltzenburg M, Charnay P, El Manira A, Ibañez CF, Ernfors P

Histone H2AX-dependent GABA(A) receptor regulation of stem cell proliferation.

Nature 451: 460-464, 2008

Kyriakatos A, El Manira A

Long-term plasticity of the spinal locomotor circuitry mediated by endocannabinoid and nitric oxide signaling.

Journal of Neuroscience 27: 12664-12674, 2007

Gabriel JP, Mahmood R, Walter AM, Kyriakatos A, Hauptmann G, Calabrese RL, El Manira A

Locomotor pattern in the adult zebrafish spinal cord in vitro.

Journal of Neurophysiology 99: 37-48, 2008

El Manira A, Kyriakatos A, Nanou E, Mahmood R

Endocannabinoid signaling in the spinal locomotor circuitry.

Brain Research Review 57: 29-36, 2008

Hess D, Nanou E, El Manira A

Characterization of Na+-activated K+ currents in larval lamprey spinal cord neurons.

Journal of Neurophysiology 97: 3484-3493, 2007

Professor Abdel El Manira

Work:
08-524 869 11
Fax:
08-34 95 44
E-mail:
Department of Neuroscience
Karolinska Institutet
Retzius väg 8
S-17177 Stockholm, Sweden

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