Genes for Autism and Intellectual Disabilities

RASopathies
The Ras/MAPK intracellular signaling pathway is fundamental for the regulation of neuronal development and function and RASopathy-inducing germline mutations are associated with varying degrees of neurocognitive impairment and autism. In turn, alterations in this pathway have been reported in mouse models of intellectual disabilities and autism spectrum disorders. However, the precise neuronal mechanisms underlying the neurocognitive and behavioral disturbances in RASopathies are still far from being understood. We investigate the effects of specific gain-of-function mutations in the RAS/MAPK pathway on neuronal network functions and control of behavior.

The Image shows a labelling neuronal fibres in the hippocampus, a key structure for learning and memory. We investigate how the formation of fibres and proper connections between cells is disturbed in RASopathy models.

 

Synaptopathies
Deficits in the development of synaptic connections between cells can result is severe  disturbances of information processing in the brain. Cognitive deficits, disturbance of social and emotional behaviour and even seizures can be the outcome. We investigate the role of synaptic proteins such as the presynaptic organiser Bassoon in the development of particular subtypes of neurons and their consequence for these behaviours.

 

Selected Publications

Annamneedi A, Caliskan G, Müller S, Montag D, Budinger E, Angenstein F, Fejtova A, Tischmeyer W, Gundelfinger E.D, Stork O. Ablation of the presynaptic organizer Bassoon in excitatory neurons retards dentate gyrus maturation and enhances learning performance. Brain Struct Funct. 2018 Jun 18; 223:3423–3445. doi: 10.1007/s00429-018-1692-3.

Altmüller F, Pothula S, Annamneedi A, Nakhaei-Rad S, Montenegro-Venegas C, Pina-Fernández E, Marini C, Santos M, Schanze D, Montag D, Ahmadian MR, Stork O, Zenker M, Fejtova A. Aberrant neuronal activity-induced signaling and gene expression in a mouse model of RASopathy. PLoS Genet. 2017 Mar;13(3):e1006684. Correction: 2017 Jun;13(6):e1006843.

 

Funding

BMBF Network GeNeRARe, subproject 8: GABAergic neurocognitive defects in mouse RASopathy models

PI: Prof. Dr. Oliver Stork

Researcher: M.Sc. Yunus Emre Demiray

 

LSA Fellow Project: Role of Bassoon in interneuron (dys-)function related to neuropsychiatric disorders

PI: Dr. Anil Annamneedi