Center for Psychiatric Neurosciences                                                                            Français

Laboratory on Research on the Neurobiology of Anxiety

Contact information :

Centre de Neurosciences Psychiatriques (CNP)
Site de Cery
CH-1008 Prilly-Lausanne       location plan
Switzerland
Tél. ++41 (0)21 643 69 54/65 08
Fax. ++41 (0)21 643 69 50
E-mail: Ron.Stoop@unil.ch

Group leader :

Dr. Ron Stoop, Ph.D. Ir., PD MER Ron Stoop at FBM, Lausanne University

Current collaborators :

• Dr. Alexandre Charlet, Postdoctoral research
• Mrs. Ruifang Niu, graduate student doctoral thesis
• Mr. Marios Abatis, graduate student doctoral thesis
• Mr. Matthieu Perrenoud, Master student in medicine
• Mrs. Isabel De Araujo Salgado, Master student in biology
• Mr. Jerome Wahis, Master student in biology
• Mr. Damien Chatelan, CFC biology laboratory assistant, in training

Previous collaborators :

• Dr. Daniel Huber
• Dr. Benoit Zuber
• Dr. Nicholas Grandchamps
• Mr. Martial Girardet
• Mr. M. Reza Hassan-Zade
• Mrs Camille Robinet
• Mr. Cedric Laederman
• Mrs. Stephanie Lefebvre
• Mrs. Taisia Terretaz
• Mrs. Daphne Truan
• Dr. Erwin van den Burg
• Mrs. Tesa Menendez
• Mr. Nicolas Pochon
• Dr. Anouchka Pickenhagen
• Dr. Daniele Viviani

Description :

What are the physiological mechanisms at the basis of fear and anxiety ? How is it that certain noises in the middle of the night can scare us, while a similar sound during daytime has no such effect ? Which mechanisms underlie our fear thresholds and our bodily reactions to fear ? It seems that there are individual levels and sustained anxiety and fear can manifest themselves in various ways : in one person they can lead to cardiovascular problems while in others the gastrointestinal system starts to give problems. The precise physiological reasons for these, however, remain still largely unknown.

It is these kinds of questions to which our group is trying to find answers. We meanwhile know that one region in the brain is particularly involved in our anxiety and fear responses : the amygdala, a cluster of nuclei situated in the temporal lobe, anterior to the hippocampus with which is maintains strong anatomical and functional connections. The amygdala receives a large variety of different sensory inputs (auditif, visual, olfactory and gustatory) and projects to a great number of nuclei in the brain stem that control our visceral reactions. To study the regulation of these functions by the amygdala we use the rat as animal model.

The rat is a very interactif companion with an important social life. It resembles us in many aspects. The approach we have chosen consists of a combination of in vitro and in vivo experiments. For the in vitro part, we have established in Cery a laboratory with various electrophysiological set-ups to record neurophysiological signalling in slices of rat brain using extracellular, intracellular and whole-cell patch-clamp methods. For the in vivo part, we use telemetric devices that allow us to measure physiological responses of animal that are exposed to light fearful stimuli. In this was we can follow increases in heart rate, blood pressure respiratory rhythm or intestinal motility in the freely behaving rat on a continuous basis.

Research projects :

Effects of Neuropeptides on the emotional expression of fear.

Fear, anxiety, stress and addiction are behavior that find their origin in the limbic system, where we also find the amygdala, entorhinal cortex and hippocampus. The amygdala has recently been defined as a key region for regulation of emotions and emotional memories. Oxytocin and vasopressin are two neuropeptides that are implicated in various physiological functions. Locally injected in the amygdala, they modulate our reactions of fear in opposite manner. In our laboratory, we have recently published findings that point to a new model for the neurophysiological mechanisms that underlie their opposite behavioural effects (Huber et al, Science 305, 2005). Following this discovery, we are currently continuing research in  comparaing the different effects of vasopressin and oxytocin in animal models in vivo and in brain slices in vitro. The in vivo research entails studies on the behaviour of rodents combined with telemetrical measurements (telemetric devices are implanted intraperitoneally) to mesure on-line changes in different parameters of the autonomic nervous system that are modulated by amygdala activity. These comprise temperature, blood pressure, and cardiac and respiratory rhythms. The in vitro approach includes different electrophysiological techniques combines with retrograde tracing of projections from the amygdala to the brain stem using fluorescent latex microspheres.

Effects of epileptic activity on emotions and emotional memories.

Temporal lobe epilepsie (TLE) is the most common form of epilepsy and remains untili today resistant to long-term pharmacological treatment. Moreover, a large number of patients that suffer from this epilepsy often also exhibit signs of anxiety disorders. Symptoms of these manifest themselves in between crises and can be more hindering then the crises themselves. The two structures that are mostly affected by TLE are the hippocampus and the amygdala. The amygdala is also important for attributing emotional values to our sensory stimuli. Our laboratoy is interested in assigning which role the amygdala plays in emotional disorders, and more precisely anxiety and fear disorders.

More specifically, we are interested to examine which changes, on the synaptic level, can be found in the amygdala following epileptic activity. We think these changes are at the basis of the development of anxiety disorders in patients that suffer from TLE. To this purpose, we have developed a horizontal slice preparation of the rat brain that contain amygdala and hippocampus and interconnections between these structures. In these slices we can induce epileptiform activity by adding the GABA(A) receptor antagonist bicuculline.

To address the above questions we make use of different electrophysiological techniques such as extracellular, intracellular and patch-clamp recordings in slices of amygdala and hippocampus, followed by immunohistochemical measurements. With these techniques it is possible to study the speed and extent of propagation of epileptiform bursting. Furthermore we are currently developing an in vivo model in which local, short term application of bicuculline in the amygdala of rodents leads to long-term enhancement of anxiety and fear in rodent. We maintain a close collaboration with the department of neurosurgery in the Lausanne University Hospital, through which we regularly participate in meetings and seminars, but also evaluations and operations on epileptic patients.

Teaching tasks :

Teaching to 2^nd and 3^rd year medical students :

• Module 3.4, "Système limbique : mémoire & émotions"
• Demonstrations of the Nervous System

Teaching to master's students in biology at UNIL, Neuroscience specialization :

• Module "Introduction à la neurobiologie"
• Module "Long Term Potentiation and Long Term Depression"

Teaching to 3^rd year biology students at EPFL (6^th semester) :

• Memory and Neuronal Plasticity
• Neurobiology of Emotions

Teaching at the Lemanic Neuroscience Doctoral School :

• Introduction to Cellular and Molecular Neurobiology
• Neuronal basis of emotions
• Neurosciences Psychiatriques
• Les réponses émotionnelles: efférences amygdaliennes
• Une émotion très étudiée : la peur

Continued Education:

• "Anxiété: des neurosciences à la clinique, de la clinique aux neurosciences", Département de psychiatrie du CHUV
• Cours postgradué pour la spécialisation en psychiatrie et psychothérapie, CEPUSPP : "Troubles de l’anxiété"
• "Mémoire et psychopathologie : des concepts à la clinique", Département de psychiatrie du CHUV

Keywords :

anxiety, fear, amygdala, hippocampus, neuropeptides, oxytocin, vasopressin, epilepsy, electrophysiology, patch-clamp, telemetry

National and international collaborations :

• Dr. Claudio Pollo et Dr. Etienne Pralong, Service de Neurochirurgie, CHUV
• Prof. Pierrick Poisbeau et Prof. Pierre Veinante, Université Louis Pasteur, Strasbourg
• Prof. Bai Lu, NIMH, Bethesda, USA
• Prof. Muming Poo, Institute of Neuroscience, Chinese Academy of Sciences, Shanghai.
• Prof. Roy Daniel, M.Ch. (Neurosurgery), Christian Medical College, Vellore, India

Recent Publications

• H. Sophie Knobloch, Alexandre Charlet, Lena C. Hoffmann, Marina Eliava, Sergey Khrulev, Ali H. Cetin, Pavel Osten, Martin K. Schwarz, Peter H. Seeburg, Ron Stoop, and Valery Grinevich, Evoked Axonal Oxytocin Release in the Central Amygdala Attenuates Fear Response, Neuron 73, (3), pp. 553-66, 2012 [DOI]
    
• Daniele Viviani, Alexandre Charlet, Erwin van den Burg, Camille Robinet, Nicolas Hurni, Marios Abatis, Fulvio Magara, Ron Stoop, Oxytocin Selectively Gates Fear Responses Through Distinct Outputs from the Central Amygdala, Science 333(6038), pp. 104-7, 2011 [DOI]
    
• Daniel Huber, Pierre Veinante, Ron Stoop, Vasopressin and Oxytocin Excite Distinct Neuronal Populations in the Central Amygdala, Science 308(5719), pp. 245-8, 2005 [DOI]