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The broad theme of my research interest span from the basic understanding of neuronal computations in cortical networks to drug discovery aimed at treating brain disease states, as in epilepsy or cerebellar ataxia. Ongoing lines of investigations in the laboratory include:
Presynaptic modulation of neurotransmitter release. How neurotransmitter molecules are released from nerve terminals is of fundamental importance in understanding the modulation of synaptic strength, and therefore the excitability of neuronal circuits. It emerges that a plethora of neurotransmitter receptors coupled to ion channels contribute to fast modulation of transmitter release at central synapses. These include GABAA, NMDA and kainate receptors. We use presynaptic recordings from single mossy fibre terminals in the hippocampus to investigate the nature of these receptors as well as their mode of activation and regulation by endogenous neurotransmitters and modulators.
Subthreshold signalling in central axons. Presynaptic depolarisation has an effect on release of neurotransmitters via a mechanism thought to involve changes in intraterminal resting Ca2+. This phenomenon termed ‘analogue coding’ allows axons to transmit graded signals in addition to coding neuronal information with action potential rate and timing.
Zinc-mediated actions in the CNS. Zinc is widely distributed in the CNS and is particularly abundant in hippocampal mossy fibres, which project from dentate granule cells to the hilus and CA3. Modulation of neurotransmitter receptors by endogenous zinc has profound implications for developmental and pathological processes, in particular epilepsy and hyperplexia, or diseases associated with zinc deficiency in adults and neonates.
Dendritic integration in neocortical neurons. We use 2-photon laser scanning microscopy and neurotransmitter uncaging to map single dendritic inputs and analyse their contribution to somatic voltage in layer 2-3 neocortical neurons. This approach is complemented by neuronal modelling based on realistic morphology and experimentally determined biophysical parameters.
Drug discovery. In collaboration with Dr Stephen Hilton from the Medicinal Chemistry Group at the School of Pharmacy we have synthesized a compound based on small molecule libraries technology which seems promising for treating memory related disorders associated with Alzheimer's disease, dementia or Parkinson's disease. The compound facilitates excitatory synaptic transmission and reduces the threshold for LTP induction at glutamatergic synapses in the hipppocampus. We are currently investigating the molecular targets of this compound as well as its mechanisms of action.
The broad theme of my research interest span from the basic understanding of neuronal computations in cortical networks to drug discovery aimed at treating brain disease states, as in epilepsy or cerebellar ataxia. Ongoing lines of investigations in the laboratory include:
Presynaptic modulation of neurotransmitter release. How neurotransmitter molecules are released from nerve terminals is of fundamental importance in understanding the modulation of synaptic strength, and therefore the excitability of neuronal circuits. It emerges that a plethora of neurotransmitter receptors coupled to ion channels contribute to fast modulation of transmitter release at central synapses. These include GABAA, NMDA and kainate receptors. We use presynaptic recordings from single mossy fibre terminals in the hippocampus to investigate the nature of these receptors as well as their mode of activation and regulation by endogenous neurotransmitters and modulators.
Subthreshold signalling in central axons. Presynaptic depolarisation has an effect on release of neurotransmitters via a mechanism thought to involve changes in intraterminal resting Ca2+. This phenomenon termed ‘analogue coding’ allows axons to transmit graded signals in addition to coding neuronal information with action potential rate and timing.
Zinc-mediated actions in the CNS. Zinc is widely distributed in the CNS and is particularly abundant in hippocampal mossy fibres, which project from dentate granule cells to the hilus and CA3. Modulation of neurotransmitter receptors by endogenous zinc has profound implications for developmental and pathological processes, in particular epilepsy and hyperplexia, or diseases associated with zinc deficiency in adults and neonates.
Dendritic integration in neocortical neurons. We use 2-photon laser scanning microscopy and neurotransmitter uncaging to map single dendritic inputs and analyse their contribution to somatic voltage in layer 2-3 neocortical neurons. This approach is complemented by neuronal modelling based on realistic morphology and experimentally determined biophysical parameters.
Drug discovery. In collaboration with Dr Stephen Hilton from the Medicinal Chemistry Group at the School of Pharmacy we have synthesized a compound based on small molecule libraries technology which seems promising for treating memory related disorders associated with Alzheimer's disease, dementia or Parkinson's disease. The compound facilitates excitatory synaptic transmission and reduces the threshold for LTP induction at glutamatergic synapses in the hipppocampus. We are currently investigating the molecular targets of this compound as well as its mechanisms of action.
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Ghada I Aboheimed,Maha M AlRasheed, Sultan Almudimeegh,Karla A Peña-Guerra,Kelly J Cardona-Londoño,Mustafa A Salih,Mohammed Z Seidahmed,Futwan Al-Mohanna,Dilek Colak,Robert J Harvey,Kirsten Harvey,Stefan T Arold,
The Journal of biological chemistryno. 7 (2022): 102018-102018
G. Aboheimed,M. ALRasheed,M. Salih,M. AlOwain,M. Alsagob,R. Almass, L. AlQuait,R. Harvey, H. AlDhallaan, O. Dabbagh,A. Ruiz,N. Kaya
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