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 focusing 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.
Please watch the video featuring Dr. Schmid’s research:
We use two operational measures for sensory filtering in order to study the underlying mechanisms: Habituation and prepulse inhibition of startle. Please see video below in order to learn how we measure these:
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 (e.g. schizophrenia and autism spectrum disorders). 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 behaviour. One of our specific targets is the voltage- and calcium activated big potassium calcium channel (BK channel) that is abundantly expressed in the brain and fine tunes synaptic efficacy. BK channel knock-out mice show no short-term habituation of startle and disrupted prepulse inhibition (see below). Consequently, they also show disruptions in higher cognitive functions such as spatial learning. In a different project, we study the role of cholinergic neurotransmission in different forms of habituation.
Startle responses are inhibited by a preceding non-startling stimulus (prepulse). Prepulse inhibition (PPI) is considered to represent a ubiquitous sensory filter mechanism in our brain that protects the processing of salient stimuli. PPI was originally developed to describe sensory filtering deficits in schizophrenia patients. An impairment of PPI is not only one of the major symptoms in schizophrenia, but prevalent also in several other neurological disorders. We explore neurotransmitters, receptors and second messenger pathways that mediate PPI in rodents. One focus is on the role of cholinergic neurons in PPI and in sensory filtering in general.
We use a wide variety of methods in our lab, ranging from behavioural experiments with rats and mice to cellular/molecular work. We combine behavioural experiments with different disease animal models, and/or with systemic and stereotaxic injections. We also perform in-vivo and in vitro (patch-clamp) recordings in brain slices, voltage-sensitive dye imaging and optogenetic approaches (in vivo and in vitro). Finally we do histological and immunohistochemical analysis of brain tissues.
For more information about the research we do in this lab, please read this article from International Innovations (Issue 171 – A Passion for Progress). The article includes a brief interview with Dr. Susanne Schmid and a well-written account on the work we are currently doing in the lab.