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Prof Vincenzo Crunelli 


My research focuses on the cellular and network mechanisms operating in the thalamus and cortex during sleep and absence epilepsy. Recently, we also developed an interest in the mechanisms involved in astrocyte-neuron signalling. My multi-disciplinary group uses a combination of electrophysiological, morphological, immunocytochemical and confocal imaging techniques both in normal and transgenic in vivo and in vitro animal models, as well as a computational approach for simulations of neuronal and astrocytic network activities.

Sleep mechanisms

One of the most fundamental electrical activities that occurs in thalamic and cortical neurons during natural sleep is the ‘slow sleep oscillation’. The top panel in Figure 1 below shows a typical example of this activity recorded from a thalamic neuron.

Sleep Mechanisms

Figure 1

Link to Full Image  26.8 Kb

The ‘slow sleep oscillation’ is characterized by the presence of two membrane potentials (called UP and DOWN states), which are generated by the switching ‘on’ and ‘off’ of the window component of the low-voltage activated, T-type Ca2+ current (I T). In the bottom panel of Figure 1, the other two neuronal currents that play a critical role in the slow oscillations are illustrated, i.e. I h, hyperpolarization-activated Na +/K + current, and I CAN, Ca2+-activated non-selective cation current. Further details in our publications: Hughes et al., Neuron 33 (2002) 947-958; Blethyn et al., Journal of Neuroscience 26 (2006) 2474-2486; Crunelli et al., Cell Calcium 40 (2006) 175-190; and Destexhe et al., Trends in Neuroscience 30 (2007) 334-342.

Pathophysiological mechanisms of Absence Epilepsy

Absence epilepsy

Figure 2

Link to Full Image  47.0 Kb

Absence epilepsy is a non-convulsive form of epilepsy that mainly affects children and teenagers. Each seizure consists of a sudden and brief impairment of consciousness, which is accompanied by a vacant stare, lack of response to external stimuli, and the appearance in the EEG of a characteristic pathological activity, called a ‘spike-and-wave discharge’ (illustrated in Figure 2A, right).

The ‘spike-and-wave discharge’ is generated by the abnormal electrical activities of cortical and thalamic neurons (depicted in Figure 2B-D, colour code refers to the different cell types illustrated in the schematic diagram). Note the very strong firing of the GABAergic neurons in the nucleus reticularis thalami (NRT) (see movie below) and the electrical silence of the thalamocortical (TC) neurons.

Since TC neurons are those that transfer sensory stimuli, their hyperpolarization and lack of firing explain why children are unresponsive during an absence seizure.

Further details in our publications: Crunelli and Leresche, Nature Reviews Neuroscience, 3 (2002) 371-382; Slaght et al. Journal of Neuroscience 22 (2002) 2323-2334; and Manning et al., Neuroscience 123 (2004) 5-9.

Astrocyte-neuron signalling

Astrocytes (a type of glial cells)

Figure 3A

Astrocytes (a type of glial cells) are no longer thought of as only providing mechanical support for neurons and controlling the extracellular concentration of key ions and metabolites, but have been shown to contribute actively to the transfer of neuronal information at the synaptic level.

Since astrocytes are non-excitable cells their ‘activation’ consists of transients rises in intracellular Ca2+ which then leads to the vesicular release of transmitters, including glutamate and ATP.

 

Astrocyte released substance

Figure 3B

These astrocytically released substances then act on neurons (preferentially activating NMDA receptors) modulating transmitter release or controlling synaptic efficacy. Indeed, astrocytes can even generate spontaneous and localized, intracellular Ca2+ waves in the absence of any neuronal activity.

Further details in our publications: Parri et al., Nature Neuroscience 4 (2001) 803-812; Parri et al., Neuroscience 120 (2003) 979-992; and Parri and Crunelli Nature Neuroscience 10 (2007) 271-273

 

Group Facilities

My laboratory is equipped with six electrophysiological stations (three for patch- and three for sharp-electrode recordings), one confocal microscope (Odyssey, Thermo Noran, USA) with in vitro patch-electrode recording facilities, one 2-photon laser scanning microscope (Ultima, Prairie Technology, USA) with in vivo and in vitro patch- and sharp-electrode recording facilities, a suite for in vivo electrical recordings and localized drug application in freely moving models, one cluster of 11 dual-processor nodes for computer simulations, in-house developed software for dynamic clamp experiments, and facilities for post-hoc morphological and immunocytochemical analysis of neurons and astrocytes.

Current Grants

Cellular thalamic mechanisms under physiological and pathological conditions
Source: The Wellcome Trust
Duration: 5 years (from October 2003) (Programme Grant)
Amount: £ 1,246,652

Neuronal thalamic gap junctions: identity, location and role in slow EEG rhythms of (patho)physiological states
Source: The Wellcome Trust
Duration: 3 years (from January 2006)
Amount: £ 239,867

Molecular and cellular investigation of neuron-astroglia interactions: Understanding brain function and dysfunction
Source: The European Union (FP7)
Duration: 4 years (from January 2008) (with 5 partners)
Amount: £ 2,104,762

Visiting Scientist

Dr Giuseppe Di Giovanni

History
I received my Ph.D. in Neuroscience from the University of Chieti, Neurology Dep., Italy. My doctoral research, at the Mario Negri Sud Institute, Italy, focused on the role of serotonin on the modulation of the central dopaminergic system. I was a postdoctoral fellow with Professor B. Bunney at Yale University, Psychiatry Dep., USA. I am a Lecturer in Human Physiology in the Medical School of the University of Palermo, Italy.

Current Research
I
am currently focused on understanding the substrates of the cellular and molecular mechanisms that underlie absence epilepsy in different models of this disease.

Senior Research Associates, Research Associates and Postgraduate Students

Dr Adam Errington

History
I was awarded my BSc in Pharmacology from the University of Sunderland in 2002 before moving to New Zealand to complete my PhD in Neuropharmacology at the University of Otago (Te Whare Wananga ó Otāgo) in Dunedin in 2006. My doctoral research was the first to identify, using electrophysiological techniques, a molecular mode of action for the novel drug Lacosamide (Mol. Pharmacol., 2007) which is currently undergoing Phase III clinical trials for use in the treatment of epilepsy and neuropathic pain.

Current Research
I am currently a postdoctoral associate investigating the properties of thalamocortical neuron dendrites and their role in physiological network oscillations associated with sleep. To achieve this I use electrophysiology, mostly the patch clamp technique, coupled with 2-photon laser scanning microscopy and calcium imaging.

Dr Magor Lorincz

History
I graduated from the Babeş-Bolyai University ( Cluj-Napoca, Romania) where I obtained a BsC. in Biology in 2002. I joined the group of Prof. Gabor Juhasz at Lorand Eötvös University in Budapest to complete a PhD on the mechanism of physiological and pathological synchronization in the visual system in 2007.

Current Research
I am studying cellular and network mechanisms of oscillations in the thalamocortical system using a combination of in vitro and in vivo electrophysiological techniques.

Dr. Tibor I. Tóth

History
I graduated from the Ilmenau Institute of Technology (Germany) as MSc. in Biomedical Engineering and MSc. in Mathematics. I received my Ph.D. in Biological Cybernetics jointly from the Hungarian Academy of Sciences and the Ilmenau Institute of Technology.

My previous working affiliations include: the National Institute of Occupational Health, Budapest, Hungary; Tohoku University, Sendai, Japan; University of Copenhagen, Denmark; Columbia University, New York, USA.

Current research
Modelling of nonlinear electrical behaviour of neurones of the central nervous system. Application of mathematical methods of nonlinear analysis to neuronal systems.

Ms Sarah Fyson

History
In 2005 I graduated at Cardiff University obtaining my BSc in Neuroscience. After taking time to travel, I returned to Cardiff and began my PhD in October 2006.

Current Research
Using the patch-clamp technique, I am investigating the properties of a tonic GABA A receptor current in thalamocortical cells using pharmacological models of absence epilepsy.

Mr Timothy Gould

Using confocal imaging in freshly isolated slices, I am studying astrocyte-neuron signalling in the ventrobasal thalamic complex, and in the nucleus accumbens and in the ventral tegmental area.

Ms Jill Watson

History
I graduated with a BSc. in Neuroscience from Cardiff University in 2007. My degree included a 1 year placement at the Mario Negri Institute of Pharmacological Research under the supervision of Dr Luigi Cervo. While there I used self-administration and Conditioned place preference to study the reinforcing and rewarding effects of GHB in rats.

Current Research
Using sharp electrode recording in genetic models of absence epilepsy I am investigate the intrinsic and network properties of the proposed 'initiation site' of absence seizure that is located in the perioral region of the somatosensory cortex.

Collaborations

Dr Zsuzsanna EMRI and Dr Karoli ANTAL
Chemical Research Center, Institute of Chemistry, Pusztaszeri ut 59-67, Budapest 1025, Hungary

Dr Nathalie LERESCHE
Département de Neurobiologie Cellulaire Institut des Neurosciences, Université Pierre et Marie Curie, Paris, France

Prof. Hannah MONNIER
Department of Clinical Neurobiology, University Hospital, Heidelberg, Germany

Prof. John PARNAVELAS
Department of Anatomy & Developmental Biology, University College London, London, UK

Prof. Hee-Sup SHIN
Center for Neural Science, Korea Institute of Science and Technology, Seoul, Republic of Korea

Prof. Klaus WILLECKE
Department of Genetics, University of Bonn, Bonn, Germany