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Publications

M2
Stage
Informations pratiques
LNC2
Laboratoire:

LNC2

Équipe
Mathematics of Neural Circuits
Responsable
Boris Gutkin
Durée du stage
5-6 months
Langue
French and/or English

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration from early mild cognitive impairment (MCI)) to dementia. The multi-scale causes of such pathologies, from the subcellular to the brain level, remain elusive to experimental approaches alone. The masters project is geared towards developing new models of cell-specific pathologies associated with AD and examining their effects at teh population and functional level. Specifically the models developed will identify AD-linked beta amyloid (Ba) role in neural activity alterations and cognitive impairments. The models, constrained by state-of-the-art data, will relate abnormalities at the receptor and cellular level with deficits in cognitive functions. We will focus on data-based modeling of early AD when low levels of Ba interact with elements of the neuronal circuit (data from collaborator labs). We will examine the Ba action through nicotinic acetylcholine receptors (NNRs) on brain activity seen in AD/MCI: notably the hyperfrontality and perturbations of the theta rhythm.

The intern taking part in this project will work on one of the two aspects to specifically delineate the role of Ba action on NNRs of multiple subtypes (homomeric alpha7, heteromeric alpha7, beta2, alpha 5) in 1. the progressive onset of fronto-cortical hyperactivity or 2. the role of Ba-a7 action on failure of theta rhythm in the hippocampus. This they will be able to participate in one of two specific Aims:

Aim1: Guided by cutting edge data from Maskos lab (Pasteur Institute), we will build on our earlier developed models of NNR action in PFC circuitry to discover precise mechanisms by which soluble Ba acts on the NNR expressed on inhibitory circuitry to provoke hyperactivity. 
 

Aim2: Guided by data from Yakel lab (NIEHS) our framework will extend to a mesoscopic spiking circuit model of theta induction in the hippocampus and Ba-a7 induced dynamics pathology. 

Aim3: We will use these to model key cognitive tasks (e.g. working memory) and identify links between Ba-NNR pathways and MCI. We will profile potential nicotinic agents for functional amelioration. 

Intern will receive training in computational modelling, analysis and the neurobiology of AD. Intern will take part in the scientific life of the GNT: seminars, lectures, presentations.

M2
Internship
Informations pratiques
LNC2
Laboratoire:

LNC2

Équipe
Mathematics of Neural Circuits
Responsable
Boris Gutkin
Durée du stage
5-6 months
Langue
French and/or English

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration from early mild cognitive impairment (MCI)) to dementia. The multi-scale causes of such pathologies, from the subcellular to the brain level, remain elusive to experimental approaches alone. The masters project is geared towards developing new models of cell-specific pathologies associated with AD and examining their effects at teh population and functional level. Specifically the models developed will identify AD-linked beta amyloid (Ba) role in neural activity alterations and cognitive impairments. The models, constrained by state-of-the-art data, will relate abnormalities at the receptor and cellular level with deficits in cognitive functions. We will focus on data-based modeling of early AD when low levels of Ba interact with elements of the neuronal circuit (data from collaborator labs). We will examine the Ba action through nicotinic acetylcholine receptors (NNRs) on brain activity seen in AD/MCI: notably the hyperfrontality and perturbations of the theta rhythm.

The intern taking part in this project will work on one of the two aspects to specifically delineate the role of Ba action on NNRs of multiple subtypes (homomeric alpha7, heteromeric alpha7, beta2, alpha 5) in 1. the progressive onset of fronto-cortical hyperactivity or 2. the role of Ba-a7 action on failure of theta rhythm in the hippocampus. This they will be able to participate in one of two specific Aims:

Aim1: Guided by cutting edge data from Maskos lab (Pasteur Institute), we will build on our earlier developed models of NNR action in PFC circuitry to discover precise mechanisms by which soluble Ba acts on the NNR expressed on inhibitory circuitry to provoke hyperactivity. 
 

Aim2: Guided by data from Yakel lab (NIEHS) our framework will extend to a mesoscopic spiking circuit model of theta induction in the hippocampus and Ba-a7 induced dynamics pathology. 

Aim3: We will use these to model key cognitive tasks (e.g. working memory) and identify links between Ba-NNR pathways and MCI. We will profile potential nicotinic agents for functional amelioration. 

Intern will receive training in computational modelling, analysis and the neurobiology of AD. Intern will take part in the scientific life of the GNT: seminars, lectures, presentations.

Chapitre d'ouvrage  

Gutkin, B., Pinto, D. & Ermentrout, G. (2001). Mathematical Neuroscience: From Neurons to Circuits to Systems. Deas Mathematicas (Mathematical Webs)

Article dans une revue internationale  

Gruber, A., Dayan, P., Gutkin, B. & Solla, S. (2006). Dopamine modulation in the basal ganglia locks the gate to working memory. Journal of Computational Neuroscience, 20(2), 153-166. doi:10.1007/s10827-005-5705-x

Article dans une revue internationale  

Gutkin, B. & Ermentrout, G. (2006). Neuroscience: Spikes too kinky in the cortex? Nature, 440(7087), 999-1000. doi:10.1038/440999a

Article dans une revue internationale  

Gutkin, B., Dehaene, S. & Changeux, J. (2006). A neurocomputational hypothesis for nicotine addiction. Proceedings of the National Academy of Sciences of the United States of America, 103(4), 1106-1111. doi:10.1073/pnas.0510220103

Article dans une revue internationale  

Jeong, H. & Gutkin, B. (2007). Synchrony of neuronal oscillations controlled by GABAergic reversal potentials. Neural Computation, 19(3), 706-729. doi:10.1162/neco.2007.19.3.706

Article dans une revue internationale  

Brumberg, J. & Gutkin, B. (2007). Cortical pyramidal cells as non-linear oscillators: Experiment and spike-generation theory. Brain Research, 1171(1), 122-137. doi:10.1016/j.brainres.2007.07.028

Article dans une revue internationale  

Bobashev, G., Costenbader, E. & Gutkin, B. (2007). Comprehensive mathematical modeling in drug addiction sciences. Drug and Alcohol Dependence, 89(1), 102-106. doi:10.1016/j.drugalcdep.2006.12.029

Chapitre d'ouvrage  

Gutkin, B. & Stiefel, K. (2007). Phase-resetting curves and neuromodulation of action potential dynamics in the cortex. (Vol. 40, pp. 14-15).

Article dans une revue internationale  

Stiefel, K., Gutkin, B. & Sejnowski, T. (2008). Cholinergic neuromodulation changes phase response curve shape and type in cortical pyramidal neurons. PLoS ONE, 3(12). doi:10.1371/journal.pone.0003947

Article dans une revue internationale  

Gutkin, B., Jost, J. & Tuckwell, H. (2008). Random perturbations of spiking activity in a pair of coupled neurons. Theory in Biosciences, 127(2), 135-139. doi:10.1007/s12064-008-0039-7

Article dans une revue internationale  

Gutkin, B., Jost, J. & Tuckwell, H. (2008). Transient termination of spiking by noise in coupled neurons. EPL, 81(2). doi:10.1209/0295-5075/81/20005

Article dans une revue internationale  

Graupner, M. & Gutkin, B. (2009). Modeling nicotinic neuromodulation from global functional and network levels to nAChR based mechanisms. Acta Pharmacologica Sinica, 30(6), 681-693. doi:10.1038/aps.2009.87

Article dans une revue internationale  

Tegnér, J., Compte, A., Auffray, C., An, G., Cedersund, G., Clermont, G., Gutkin, B., Oltvai, Z., Stephan, K., Thomas, R. & Villoslada, P. (2009). Computational disease modeling - Fact or fiction? BMC Systems Biology, 3. doi:10.1186/1752-0509-3-56

Article dans une revue internationale  

Tuckwell, H., Jost, J. & Gutkin, B. (2009). Inhibition and modulation of rhythmic neuronal spiking by noise. Physical Review E - Statistical, Nonlinear, and Soft Matter Physics, 80(3). doi:10.1103/PhysRevE.80.031907

Article dans une revue internationale  

Remme, M., Lengyel, M. & Gutkin, B. (2009). The role of ongoing dendritic oscillations in single-neuron dynamics. PLOS Comp. Bio. , 5(9)

Article dans une revue internationale  

Gutkin, B., Tuckwell, H. & Jost, J. (2009). The Phenomenon of Inverse Stochastic Resonance. Naturwissenschaften, 96(9), 1091-7

Article dans une revue internationale  

Graupner, M., Ahmed, S. & Gutkin, B. (2009). Modelling dynamics of addiction. Pharmacopsychiatry, 42(Suppl 1), S144-52

Article dans une revue internationale  

Stiefel, K., Gutkin, B. & Sejnowski, T. (2009). Simulation of effects of cholinergic modulation of phase response curves. J Comp Neurosci, 29(2)

Article dans une revue internationale  

Remme, M., Lengyel, M. & Gutkin, B. (2010). Democracy-independence trade-off in oscillating dendrites and its implications for grid cells. Neuron, 66(3), 429-437. doi:10.1016/j.neuron.2010.04.027

Article dans une revue internationale  

Muller, L., Brette, R. & Gutkin, B. (2011). Spike-timing dependent plasticity and feed-forward input oscillations produce precise and invariant spike phase-locking. Frontiers in Computational Neuroscience, 15(5), 45. doi:10.3389/fncom.2011.00045

Article dans une revue internationale  

Jedlicka, P., Deller, T., Gutkin, B. & Backus, K. (2011). Activity-dependent intracellular chloride accumulation and diffusion controls GABA A receptor-mediated synaptic transmission. Hippocampus, 21(8), 885-898. doi:10.1002/hipo.20804