![Cezar Tigaret](https://profiles-cardiff.imgix.net/attachments/3667?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Dr Cezar Tigaret
(he/him)
Hodge Lecturer in Neuroscience, Neuroscience and Mental Health Innovation Institute
- TigaretC@cardiff.ac.uk
- +44 29206 88330
- Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ
- Available for postgraduate supervision
Overview
I aim to understand the causality between psychiatric risk factors and the emergence of symptoms and cognitive deficits in psychiatric illness, underpinned by alterations in neural synaptic and circuit functions.
Recent studies have found a complex genetic risk in psychiatric illnesses such as schizophrenia and bipolar disorder. These discoveries implicate alterations in the function of brain cells and how they communicate with each other, in the common symptoms found in psychoses. There is now an urgent need to translate these discoveries into more effective therapies based on causation.
I have a special interest in synaptic plasticity as a principal cellular mechanism of associative learning which forms the basis of our reasoning and capacity to represent and adapt to the environment and is disrupted in psychosis.
I combine state-of-the-art two-photon imaging and ex vivo slice electrophysiology in animal models and in silico modeling techniques.
Publication
2023
- Indrigo, M. et al. 2023. Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2. EMBO Molecular Medicine 15(11), article number: e15984. (10.15252/emmm.202215984)
- Rodrigues, Y. E., Tigaret, C. M., Marie, H., O'Donnell, C. and Veltz, R. 2023. A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics. eLife 12, article number: e80152. (10.7554/eLife.80152)
2021
- Tigaret, C. M. et al. 2021. Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c. Molecular Psychiatry 26, pp. 1748-1760. (10.1038/s41380-020-01001-0)
2018
- Tigaret, C. M., Chamberlain, S. E. L., Sadowski, J. H. L. P., Hall, J., Ashby, M. C. and Mellor, J. R. 2018. Convergent metabotropic signalling pathways inhibit SK channels to promote synaptic plasticity in the hippocampus. Journal of Neuroscience 38(43), pp. 9252-9262. (10.1523/JNEUROSCI.1160-18.2018)
2016
- Prince, L. Y., Bacon, T. J., Tigaret, C. M. and Mellor, J. R. 2016. Neuromodulation of the feedforward dentate gyrus-CA3 microcircuit. Frontiers in Synaptic Neuroscience 8, article number: 32. (10.3389/fnsyn.2016.00032)
- Tigaret, C. M., Olivo, V., Sadowski, J. H. L. P., Ashby, M. C. and Mellor, J. R. 2016. Coordinated activation of distinct Ca2+ sources and metabotropic glutamate receptors encodes Hebbian synaptic plasticity. Nature Communications 7(1), article number: 10289. (10.1038/ncomms10289)
2015
- Glebov, O. O., Tigaret, C. M., Mellor, J. R. and Henley, J. M. 2015. Clathrin-independent trafficking of AMPA receptors. Journal of Neuroscience 35(12), pp. 4830-4836. (10.1523/JNEUROSCI.3571-14.2015)
2013
- Tigaret, C. M., Tsaneva-Atanasova, K., Collingridge, G. L. and Mellor, J. R. 2013. Wavelet Transform-Based De-Noising for Two-Photon Imaging of Synaptic Ca 2+ Transients. Biophysical Journal 104(5), pp. 1006-1017. (10.1016/j.bpj.2013.01.015)
2011
- Sainlos, M. et al. 2011. Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization. Nature Chemical Biology 7(2), pp. 81-91. (10.1038/nchembio.498)
2010
- Opazo, P., Labrecque, S., Tigaret, C. M., Frouin, A., Wiseman, P. W., De Koninck, P. and Choquet, D. 2010. CaMKII Triggers the Diffusional Trapping of Surface AMPARs through Phosphorylation of Stargazin. Neuron 67(2), pp. 239-252. (10.1016/j.neuron.2010.06.007)
2009
- Chen, P. E. et al. 2009. Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus. Learning and Memory 16(10), pp. 635-644. (10.1101/lm.1316909)
- Tigaret, C. and Choquet, D. 2009. More AMPAR Garnish. Science 323(5919), pp. 1295-1296. (10.1126/science.1171519)
2008
- Medvedev, N. I., Rodríguez-Arellano, J. J., Popov, V. I., Davies, H. A., Tigaret, C. M., Schoepfer, R. and Stewart, M. G. 2008. The glutamate receptor?2 subunit controls post-synaptic density complexity and spine shape in the dentate gyrus. European Journal of Neuroscience 27(2), pp. 315-325. (10.1111/j.1460-9568.2007.06005.x)
2006
- Thalhammer, A., Rudhard, Y., Tigaret, C. M., Volynski, K. E., Rusakov, D. A. and Schoepfer, R. 2006. CaMKII translocation requires local NMDA receptor-mediated Ca2+ signaling. EMBO Journal 25(24), pp. 5873-5883. (10.1038/sj.emboj.7601420)
- Tigaret, C. M., Thalhammer, A., Rast, G. F., Specht, C. G., Auberson, Y. P., Stewart, M. G. and Schoepfer, R. 2006. Subunit Dependencies of N-Methyl-d-aspartate (NMDA) Receptor-Induced ?-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Internalization. Molecular Pharmacology 69(4), pp. 1251-1259. (10.1124/mol.105.018580)
2005
- Specht, C. G., Tigaret, C. M., Rast, G. F., Thalhammer, A., Rudhard, Y. and Schoepfer, R. 2005. Subcellular localisation of recombinant α- and γ-synuclein. Molecular and Cellular Neuroscience 28(2), pp. 326-334. (10.1016/j.mcn.2004.09.017)
2003
- Rudhard, Y. et al. 2003. Absence of Whisker-Related Pattern Formation in Mice with NMDA Receptors Lacking Coincidence Detection Properties and Calcium Signaling. Journal of Neuroscience 23(6), pp. 2323-2332. (10.1523/JNEUROSCI.23-06-02323.2003)
1994
- Popescu, L. M. et al. 1994. K(+)-channel openers protect the myocardium against ischemia-reperfusion injury. Annals of the New York Academy of Sciences 723(1), pp. 398-400. (10.1111/j.1749-6632.1994.tb36757.x)
1992
- Prasad, M. R., Tigaret, C. M., Smith, D., Soares, H. and McIntosh, T. K. 1992. Decreased α1-adrenergic receptors after experimental brain injury. Journal of Neurotrauma 9(3), pp. 269-279. (10.1089/neu.1992.9.269)
1988
- Popescu, L. M., Hinescu, M. E., Constantinescu, S., Tigaret, C. M., Cinteză, M. and Gherasim, L. 1988. Molecular mechanism of tolerance for vasodilator nitrates. Revista de medicină internă, neurologe, psihiatrie, neurochirurgie, dermato-venerologie. Medicină internă 40, pp. 145-154.
Articles
- Indrigo, M. et al. 2023. Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2. EMBO Molecular Medicine 15(11), article number: e15984. (10.15252/emmm.202215984)
- Rodrigues, Y. E., Tigaret, C. M., Marie, H., O'Donnell, C. and Veltz, R. 2023. A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics. eLife 12, article number: e80152. (10.7554/eLife.80152)
- Tigaret, C. M. et al. 2021. Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c. Molecular Psychiatry 26, pp. 1748-1760. (10.1038/s41380-020-01001-0)
- Tigaret, C. M., Chamberlain, S. E. L., Sadowski, J. H. L. P., Hall, J., Ashby, M. C. and Mellor, J. R. 2018. Convergent metabotropic signalling pathways inhibit SK channels to promote synaptic plasticity in the hippocampus. Journal of Neuroscience 38(43), pp. 9252-9262. (10.1523/JNEUROSCI.1160-18.2018)
- Prince, L. Y., Bacon, T. J., Tigaret, C. M. and Mellor, J. R. 2016. Neuromodulation of the feedforward dentate gyrus-CA3 microcircuit. Frontiers in Synaptic Neuroscience 8, article number: 32. (10.3389/fnsyn.2016.00032)
- Tigaret, C. M., Olivo, V., Sadowski, J. H. L. P., Ashby, M. C. and Mellor, J. R. 2016. Coordinated activation of distinct Ca2+ sources and metabotropic glutamate receptors encodes Hebbian synaptic plasticity. Nature Communications 7(1), article number: 10289. (10.1038/ncomms10289)
- Glebov, O. O., Tigaret, C. M., Mellor, J. R. and Henley, J. M. 2015. Clathrin-independent trafficking of AMPA receptors. Journal of Neuroscience 35(12), pp. 4830-4836. (10.1523/JNEUROSCI.3571-14.2015)
- Tigaret, C. M., Tsaneva-Atanasova, K., Collingridge, G. L. and Mellor, J. R. 2013. Wavelet Transform-Based De-Noising for Two-Photon Imaging of Synaptic Ca 2+ Transients. Biophysical Journal 104(5), pp. 1006-1017. (10.1016/j.bpj.2013.01.015)
- Sainlos, M. et al. 2011. Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization. Nature Chemical Biology 7(2), pp. 81-91. (10.1038/nchembio.498)
- Opazo, P., Labrecque, S., Tigaret, C. M., Frouin, A., Wiseman, P. W., De Koninck, P. and Choquet, D. 2010. CaMKII Triggers the Diffusional Trapping of Surface AMPARs through Phosphorylation of Stargazin. Neuron 67(2), pp. 239-252. (10.1016/j.neuron.2010.06.007)
- Chen, P. E. et al. 2009. Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus. Learning and Memory 16(10), pp. 635-644. (10.1101/lm.1316909)
- Tigaret, C. and Choquet, D. 2009. More AMPAR Garnish. Science 323(5919), pp. 1295-1296. (10.1126/science.1171519)
- Medvedev, N. I., Rodríguez-Arellano, J. J., Popov, V. I., Davies, H. A., Tigaret, C. M., Schoepfer, R. and Stewart, M. G. 2008. The glutamate receptor?2 subunit controls post-synaptic density complexity and spine shape in the dentate gyrus. European Journal of Neuroscience 27(2), pp. 315-325. (10.1111/j.1460-9568.2007.06005.x)
- Thalhammer, A., Rudhard, Y., Tigaret, C. M., Volynski, K. E., Rusakov, D. A. and Schoepfer, R. 2006. CaMKII translocation requires local NMDA receptor-mediated Ca2+ signaling. EMBO Journal 25(24), pp. 5873-5883. (10.1038/sj.emboj.7601420)
- Tigaret, C. M., Thalhammer, A., Rast, G. F., Specht, C. G., Auberson, Y. P., Stewart, M. G. and Schoepfer, R. 2006. Subunit Dependencies of N-Methyl-d-aspartate (NMDA) Receptor-Induced ?-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Internalization. Molecular Pharmacology 69(4), pp. 1251-1259. (10.1124/mol.105.018580)
- Specht, C. G., Tigaret, C. M., Rast, G. F., Thalhammer, A., Rudhard, Y. and Schoepfer, R. 2005. Subcellular localisation of recombinant α- and γ-synuclein. Molecular and Cellular Neuroscience 28(2), pp. 326-334. (10.1016/j.mcn.2004.09.017)
- Rudhard, Y. et al. 2003. Absence of Whisker-Related Pattern Formation in Mice with NMDA Receptors Lacking Coincidence Detection Properties and Calcium Signaling. Journal of Neuroscience 23(6), pp. 2323-2332. (10.1523/JNEUROSCI.23-06-02323.2003)
- Popescu, L. M. et al. 1994. K(+)-channel openers protect the myocardium against ischemia-reperfusion injury. Annals of the New York Academy of Sciences 723(1), pp. 398-400. (10.1111/j.1749-6632.1994.tb36757.x)
- Prasad, M. R., Tigaret, C. M., Smith, D., Soares, H. and McIntosh, T. K. 1992. Decreased α1-adrenergic receptors after experimental brain injury. Journal of Neurotrauma 9(3), pp. 269-279. (10.1089/neu.1992.9.269)
- Popescu, L. M., Hinescu, M. E., Constantinescu, S., Tigaret, C. M., Cinteză, M. and Gherasim, L. 1988. Molecular mechanism of tolerance for vasodilator nitrates. Revista de medicină internă, neurologe, psihiatrie, neurochirurgie, dermato-venerologie. Medicină internă 40, pp. 145-154.
Research
Synaptic and circuit consequences of genetic variation in voltage-gated calcium channels.
What?
Voltage-gated calcium channels (VGCCs) are proteins that convert the electrical activity of neurons into fast calcium signals subserving learning and memory and regulation of gene expression in the brain.
Why?
Genetic variation in voltage-gated calcium channel subunits, and in particular, in the CACNA1C gene encoding the CaV1.2 L-type voltage-gated calcium channels (CaV1.2 L-VGCCs) is strongly associated with risk for psychoses. Recent studies indicate that most risk-associated variants of CACNA1C act to reduce the levels of CaV1.2 L-VGCCs in the brain, but the causal links to psychiatric symptoms are poorly understood.
How?
I have developed a methodological framework to interrogate the synaptic, circuit, and behavioural impact of CACNA1C mutations, in collaboration with the groups led by Prof. Jeremy Hall and Dr. Kerrie Thomas at NMHRI, and Prof. Matt W. Jones (University of Bristol). The research is aligned with the "Mind, brain and neuroscience" research theme at the College of Biomedical and Life Sciences, and integrates state-of-the-art two-photon imaging and electrophysiology with behavioural analyses.
Outcomes.
The study, published in Molecular Psychiatry in 2021, is the first to show pathway-selective deficits in Hebbian synaptic plasticity and circuit synchronization in the hippocampus, and altered hippocampal-dependent associative learning in Cacna1c+/- animals.
This study also demonstrates for the first time the rescue of neurobiological and behavioural phenotypes associated with Cacna1c haploinsufficiency using a drug with neurotrophin BDNF mimetic activity in vivo.
What next?
In 2021 I was awarded a 3-year MRC Research Grant as a sole PI, to interrogate the potential of cholinergic muscarinic and Ca2+-sensitive K+ channel drugs to rescue the consequences of reduced CaV1.2 dosage on synaptic plasticity and integration of synaptic input in neurons.
I collaborate with Prof. Frank Sengpiel (School of Biosciences) to investigate synaptic consequences of Cacna1c gain-of-function mutations in animal models of Timothy syndrome.
Research themes
Specialisms
- Neuropsychology
- Neurosciences
- neuron
- Neuropharmacology
- synaptic function