The School would like to increase the number of doctoral students interested in using molecular and cellular approaches for investigating cognition.

For example: Autism

Autism is a serious neurodevelopmental disorder with an estimated frequency of approximately 2-6 per 1000. Autistic individuals exhibit restricted, repetitive, and stereotyped patterns of behaviour, interests and activities, and they typically display severely impaired social interaction and communication. Onset is generally observed between one and three years of age, and early signs may include, e.g., failure to respond to verbal cues, avoidance of eye contact, and engagement in clearly asocial activities such as twirling or rocking. Language development is generally delayed. Although some autistic individuals are also diagnosed  with general cognitive delay or mental retardation, in many cases, the observed cognitive abnormalities are exclusively deficits in communication; thus, investigations into the neurobiology of autism enable us to answer interesting questions about the nature of emotional development and social learning.

There have been significant developments in our understanding of the genetics underlying these behavioural abnormalities in recent years, and it is clear that several genes implicated in autism-associated disorders are essential for normal synaptic transmission. Neurexins and neuroligins, for example, both associated with autism, are neuronal cell adhesion molecules that form a trans-synaptic complex. Neuroligins interact with the autism-associated Shank family of scaffolding proteins at the post-synapse, and it has been shown that aberrations in the expression levels of these proteins influence the maturation and function of glutamatergic synapses. Several other genes implicated in developmental disorders likewise affect glutamatergic synaptic transmission, and, not surprisingly, individuals with autism and related disorders have a significantly increased risk for acquiring seizure disorders in childhood.

Contact regarding topic “Autism”:

• Dr. Sarah Shoichet (E-mail)
• Professor Dietmar Schmitz (E-mail)
• Neuroscience Research Center, Charité (Link)

Contact regarding general research area “Molecular and cellular neuroscience”:

• Professor Michael Brecht (E-mail)
• Professor Helmut Kettenmann (E-mail)
• Professor Dietmar Schmitz (E-mail)

Key publications on this topic:

Beed, P. et al. (2009) GluK2-Mediated Excitability within the Superficial Layers of the Entorhinal Cortex /PLoS ONE/ 4(6).

Bourgeron, T. (2009) A Synaptic Trek to Autism. Current Opinion in Neurobiology 19:231–234.

Etherton, M.R. et al. (2009) Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments. Proc Natl Acad Sci U S A. 106(42):17998–8003.

Geschwind, D.H. (2009) Advances in Autism. Annual Review of Medicine 60:367–80.

Kim, H.G. et al. (2008) Disruption of neurexin 1 associated with autism spectrum disorder. Am J Hum Genet. 82(1):199–207.

Durand, C.M. et al. (2007) Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 39(1):25–7.

Motazacker, M. et al. (2007) A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation. /Am J Hum Genet//./ 81(4):792–8.

Jamain S. et al. (2003) Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet. 2003 May;34(1):27–9.