Mammalian brains are complex structures mediating complex behavioural tasks. It is one of the major challenges for modern Neuroscience to find out how the mammalian brain processes sensory information in order to generate the appropriate behavioural response.
Our brain is constantly bombarded with sensory information coming from the ears, eyes, nose, tongue body surface, and interior. Most of this information is filtered pre-attentively in order to allow the brain to allocate its neural resources on focussing on salient information. Many mental disorders and neurodegenerative diseases are associated with impairments of sensory filtering, which is closely related to other cognitive deficits. Our research concentrates on these early stages of sensory information processing and filtering.
Habituation is a form of sensory filtering and also 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 habituation, we use the acoustic startle response and exploratory behaviour in an open field as behavioural models. We have also developed a rodent brain slice preparation that contains a large portion of the startle pathway and allows combining patch-clamp recordings in vitro with pharmacological treatment in vivo. 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 of startle and it will be interesting to see to what extend the same mechanisms underlie habituation of exploratory behavior.
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. One focus is on the role of cholinergic neurons in PPI and in sensory filtering in general. Our results will provide more understanding about cellular dysfunction in schizophrenics and will possibly indicate new targets for pharmaceutical intervention. In a side project we also examine disruptions of midbrain cholinergic neurotransmission in Parkinson’s disease.
• Valsamis B, Schmid S (2011) Habituation and prepusle inhibition of the acoustic startle response. J. Vis. Exp. DOI: 10.3791/3446
• De Jaeger X, Guzman MS, Raulic S; Souza IA, Li AX, Schmid S, Gainetdinov RR, Caron MG, Bartha R, Prado VF, Prado MAM (2011) Genetic dissection of striatal acetylcholine functions PLOS Biology, 9(11): e1001194
• Schmid S, Azzopardi E, de Jaeger X, Prado MAM, Prado VF (2011) VAChT knock-down mice show normal prepulse inhibition but disrupted long-term habituation. Genes, Brains and Behavior, 10(4):457-64.
• 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 (2008) Cholinergic Mechanism underlying Prepulse Inhibition of the Startle Response in Rats Neuroscience 155:326-335
• 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.
• Schmid S, Fendt M (2006) Effects of the mGluR8 agonist (S)-3,4,-DCPG in the lateral amygdala on acquisition/expression of fear-potentiated startle, synaptic transmission, and plasticity. Neuropharmacology 50:154-164. IF 3.4 [Project design, supervision, manuscript – data contribution of my lab: 70%]
• 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 (2002)Synaptic plasticity in the acoustic startle pathway: the neuronal basis for short-term habituation? Eur. J. Neurosci. 16:1325-1332