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Professor Vincenzo Crunelli

Professor Vincenzo Crunelli

Professor

School of Biosciences

Users
Available for postgraduate supervision

Overview

My research focuses on the cellular and network mechanisms operating in the thalamus and cortex during sleep and absence epilepsy, focussing on both neuronal and astrocytic assemblies. My multi-disciplinary group uses a combination of electrophysiological, morphological, immunocytochemical, computational and 2-photon laser scanning microscopical techniques both in normal animals and transgenic models. These techniques are applied to in vitro (primary culture, brain slices), as well as in anaesthetized and freely behaving preparations. We also use MRI spectroscopy to measure neurotransmitters and their metabolites in the brain of children and teenagers with absence epilepsy.

I am affiliate with:

Neuroscience and Mental Health Research Institute (https://www.cardiff.ac.uk/neuroscience-mental-health)

Cardiff Sleep Network (https://www.cardiff.ac.uk/research/explore/research-units/cardiff-sleep-network)

Interested in joining my lab as a self-funded post-graduate student or a postdoc/fellow?  Please contact me by email.

Biography

HONOURS AND AWARDS

  • Fellow, Academy of Medical Sciences (elected (2010)
  • Fellow, Academia Europaea (elected 2010)
  • Fellow, Malta Chamber of Scientists (elected 2012)
  • Fellow, Learned society of Wales (elected 2012)

EDUCATION

  • Laurea (Pure Chemistry), University of Catania, Catania, Italy (1974)
  • Postdoctoral Research Associate, Laboratory of Neuropharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy (1976-1978)
  • Postdoctoral Research Associate, Medical Research Council, Neurochemical Pharmacology Unit, Cambridge, UK (1979)
  • Postdoctoral Research Associate, Center for Neuroscience, Weizmann Institute of Science, Rehovot, Israel (1980)

ACADEMIC POSITIONS

  • Wellcome Trust Research Fellow, Department of Pharmacology, St. George's Hospital Medical School, London, UK (1981-1984)
  • Wellcome Trust Lecturer, Department of Pharmacology, St. George's Hospital Medical School, London, UK (1985)
  • Lecturer in Pharmacology, Department of Pharmacology, St. George's Hospital Medical School, London, UK (1986-1988)
  • Senior Lecturer in Pharmacology, Department of Pharmacology, St. George's Hospital Medical School, London, UK (1989)
  • Senior Lecturer in Visual Science, Department of Visual Science, Institute of Ophthalmology, London, UK (1989-1991)
  • Professor of Neuroscience, School of Biosciences, Cardiff University, Cardiff, UK (1991-to date)
  • Head, Department of Physiology, Cardiff University, Cardiff, UK (1994-1998)
  • Visiting Professor, Université Pierre et Marie Curie, 9 quai Saint-Bernard, Paris, France (1998-2002)
  • Head, Neuroscience Division, School of Biosciences, Cardiff University, Cardiff, UK (2011-2015)
  • Affiliate Professor, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta (2016-to date)

EDITORSHIP

  • Editor-in-Chief, Journal of Neuroscience Methods (1999- 2017)
  • Editor, British Journal of Pharmacology (1991-1996)
  • Editor, Neuron Glia Biology (2001-2013)
  • Editor, Thalamus and Related Systems (2003-2009)
  • Editor, Journal of Neural Systems (2004-2008)
  • Advisory Editor, Xjenza Online (2012-to date)

Publications

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2002

2001

Teaching

In the School of Bioscience at Cardiff University, I teach neuroscience and neurphysiology to undergraduate science students (modules Bi2432, BI3451, Bi3452) and to dental students. In the Faculty of Medicine and Surgery at the University of Malta, I teach neuroscience and neurological diseases to medical students.

I also supervise Master and PhD students at both Universities.

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.

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 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) 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.

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

Engagement

I regularly organize short meetings and deliver lectures to the lay public on general neuroscience as well as epilepsy and sleep in Wales, Malta and Sicily. I am also a senior advisor to "Science in the City" (supported by the Maltese goverment), a yearly one week-long inititiative including public lectures, round-tables with lay members, visits to high schools, and secondary school students visits to research laboratories of the University of Malta.