Assistant Professor
Department of Anatomy & Cell Biology
Office: Medical Sciences Building, Room 470
Phone: 519-661-2111 ext. 82668
Fax: 519-661-3936
Email: susanne.schmid@schulich.uwo.ca
Mammalian brains are complex structures mediating complex behavioural tasks. It is one of the major challenges for modern Neuroscience to find out how behaviour is generated and modulated in the mammalian brain. We want to meet this challenge using a well established simple behavioural model- the startle response. Startle is easily quantifiable and mediated by a short and mostly well described pathway. Startle responses can be modulated by sensory gating mechanisms, emotions and different learning processes. The goal of our studies is to explore the cellular and molecular mechanisms underlying this behavioural plasticity. We therefore combine electrophysiological experiments (patch-clamp) with behavioural and pharmacological experiments in vivo.
Habituation is a very essential form of implicit learning; we all perform habituation learning innumerable times during a day without perceiving it. Some psychiatric disorders are accompanied by an impairment of habituation. In order to access the cellular and molecular processes that are responsible for short-term habituation of the startle response, we have developed a rodent brain slice preparation that contains a large portion of the startle pathway and allows combining patch-clamp recordings with pharmacological treatment. Using this preparation we found that afferent sensory fibres within the startle pathway are subject to synaptic depression when stimulated in a way that mimics their activity during the presentation of startle stimuli. Synaptic depression shares many features with habituation. One specific goal of our research is to explore the molecular mechanism that leads to synaptic depression and to test our hypothesis that this is the cellular mechanism underlying short-term habituation of startle. We aim to completely unravel the cellular and molecular mechanisms of short-term habituation.
Startle responses are inhibited by a preceding non-startling stimulus (prepulse). Prepulse inhibition (PPI) is considered to represent an ubiquitous sensory filter mechanism in our brain that protects the processing of sensory stimuli. An impairment of PPI is one of the major symptoms in schizophrenia and some other neurological disorders. We explore neurotransmitters, receptors and second messenger pathways that mediate PPI in rodents. Animal models for schizophrenia are included in our experiments in order to examine the difference in signalling in these animals. Our results will provide more understanding about cellular disfunction in schizophrenics and will possibly indicate new targets for pharmaceutical intervention.
• Schmid S.#, Brown T., Simons-Weidenmaier N., Weber M., Fendt M. (2010) Group III metabotropic glutamate receptors inhibit giant neurons in the caudal pontine reticular nucleus but do not mediate synaptic depression/short-term habituation of startle. J. Neuroscience, 30(31):10422-30.
• Yeomans JS#, Bosch D., Alves N., Daros A., Ure R.J., Schmid S. (2010) GABA receptors and prepulse inhibition of acoustic startle in mice and rats. Eur. J. Neurosci. 31(11): 2053-2061.
• Bosch D., Schmid S.# (2009) Cholinergic Mechanism underlying Prepulse Inhibition of the Startle Response in Rats. Neuroscience 155:326-335.
• Fendt M.*, Schmid S.* , Thakker D.R.*, Jacobson L.H.*, Callaerts-Vegh Z., Yamamota R., Mitsukawa K., Natt F., Huesken D., McAllister K., Hoyer D., van der Putten H., D’Hooge R., Flor P.J., Cryan J.F.# (2008) Activation of mGluR7 alters amygdala plasticity and facilitates extinction of fear memory. *equal contribution , Mol. Psychiatry 13:970-979.
• Bosch, D., Schmid, S. (2006) Activation of muscarine acetylcholine receptors inhibits giant neurons in the caudal pontine reticular nucleus. Eur. J. Neurosci. 24: 1967-1975.
• Simons Weidenmaier, N., Weber, M., Plappert, C., Pilz, P.K.D., Schmid, S. (2006) Synpatic depression and short-term habituation are located on the sensory part of the mammalian startle pathway. BMC Neuroscience 7: 38.
• Holscher, C., Schmid, S., Pilz, P., Van der Putten, H., Plappert, C. (2004) Metabotropic glutamate receptor subtype 7 ablation causes a selective deficit in working memory but not long-term memory formation or startle responses. Behav. Brain Res. 154: 481-783
• Schmid, S.,Simons, N.S., Schnitzler, H-U. (2003) Cellular mechanisms of the trigeminally evoked startle response. Eur. J. Neurosci. 17: 1438-1444.
• Weber, M., Schnitzler, H-U., Schmid, S. (2005) Synaptic plasticity in the auditory startle pathway: the neuronal basis for short-term habituation? Eur. J. Neurosci. 16: 1325-1332.