Molecular Mechanisms underlying Habituation in the Startle Reflex of Mammals
Final Report Abstract
Habituation is considered to be the most basic form of non-associative learning. It describes the decrease of behavioural response to repeated non-threatening sensory stimulation and therefore provides an important sensory filtering mechanism. Habituation is impaired in patients suffering from e.g schizophrenia or autism spectrum disorders, which leads to information overload in higher brain areas causing cognitive deficits. While habituation is well studied behaviourally only little is known of the underlying molecular mechanisms. The goal of the project was to advance our understanding of the molecular mechanisms that contribute to habituation and thereby possibly uncovering new drug targets to treat neurological disorders that involve sensory filtering deficits. The data obtained in this project suggests that in mammals a highly evolutionary conserved mechanism mediates short-term habituation of reflexive behavior. This mechanism has previously been described to mediate habituation in invertebrates and is now also confirmed to be relevant in mammals. The key player of this mechanism is the big potassium channel (BK channel). This is a very exciting result, since this is the first time that a molecular player of habituation has been identified in mammals. However, despite being evolutionary highly conserved, it also seems to be a very specific mechanism, since other forms of habituation appear to be mediated differently. This study not only provides us with new valuable insights into the mechanisms underlying nonassociative learning but it also lays the foundation to identify new potential drug targets for a treatment of habituation deficits in patients.
Publications
- Activation of mGluR2/3 receptors in the ventro-rostral prefrontal cortex reverses sensorimotor gating deficits induced by systemic NMDA receptor antagonists. International Journal of Neuropsychopharmacology 2013; FirstView:1–10
B Valsamis, M Chang, M Typlt, S Schmid
- Habituation of reflexive and motivated behaviour in mice with a deficiency of the α-subunit of the BK channel. Frontiers in Integrative Neuroscience 2013; 7:79
M Typlt, M Mirkowski, E Azzopardi, P Ruth, P Pilz, S Schmid
- Mice with deficient BK channel function show impaired prepulse inhibition and spatial learning, but normal working and spatial reference memory. PlosOne 2013; 8(11): e81270
M Typlt, M Mirkowski, E Azzopardi, L Ruettiger, P Ruth, S Schmid
(See online at https://doi.org/10.1371/journal.pone.0081270) - Sensorimotor gating and spatial learning in α7-nicotinic receptor knockout mice. Genes Brain and Behavior 2013; 12(4):414-23
E Azzopardi, M Typlt, B Jenkins, S Schmid
