Project ID NS-MH2024_51


Co Supervisor 1A Institute of Psychiatry, Psychology & Neuroscience, School of Academic Psychiatry, Department of Forensic and Neurodevelopmental ScienceWebsite

Co Supervisor 1B Institute of Psychiatry, Psychology & Neuroscience, School of Academic Psychiatry, Department of Forensic and Neurodevelopmental ScienceWebsite

Making sense of the world around us – The role of synapses in sensory processing

The brain is made of billions of neurons which communicate with each other via synapses. Synapse formation (synaptogenesis), function, plasticity, and maintenance – processes crucial for normal brain development and function – are of vital importance for sensory function. Differences in sensory function are common in neurodevelopmental conditions such as autism and have tremendous impact on daily lives, and as such, are a priority area for autistic people. Atypical touch perception, and reactivity to touch, have been reported in autism. Similarly, our group found sensory differences in several genetic and environmental rodent models of autism that also show synaptic deficits, differences in brain function and behavioural alterations. However, it is still not known: i) how synapses regulate sensory perception in the healthy brain, ii) how that process is affected in autism, iii) which autism-linked genetic mutations and stress-related experiences result in sensory atypicalities, and iv) how this is associated with brain neurotransmission.
These questions will be addressed in this translational PhD project combining (preclinical) mouse models and (clinical) human data. The latter will be accomplished via our collaboration with the largest autism consortium in the world (AIMS-2-TRIALS), led by KCL. This approach has the potential to develop a new biomarker for patient stratification and pave the way for development of specific and targeted (personalized) treatments.

Overarching objectives:
Year1: in vitro and in vivo examination of the role of synapse formation and function in sensory processing
Year2: examining the role of autism-related mutations in synapse and sensory functions
Year3: continuing the Year 2 experiments and testing brain neurotransmission in models and humans via magnetic resonance spectroscopy (MRS)

Skills training:
Cell culture, electrophysiology, optogenetics, animal behaviour, pharmacological treatments, immunohistochemistry, neurochemistry, clinical assessments, normative modelling and multivariate approaches (e.g. clustering techniques) for patient stratification

Representative Publications

MM Petrinovic, R Hourez, EM Aloy, G Dewarrat, D Gall, O Weinmann, J Gaudias, LC Bachmann, SN Schiffmann, KE Vogt, ME Schwab. “Neuronal Nogo-A negatively regulates dendritic morphology and synaptic transmission in the cerebellum”. PNAS, 2013. doi: 10.1073/pnas.1214255110

He J. L., Oeltzschner G., Mikkelsen M., Deronda A., Harris A. D., Crocetti D., Wodka E. L., Mostofsky S. H., Edden R. A. E. E., Puts N. A. J. (2021). Region-specific elevations of glutamate + glutamine correlate with the sensory symptoms of autism spectrum disorders. Transl Psychiatry 11: 1–35: doi: 10.1038/s41398-021-01525-1; 12.

He, J., Williams, Z., Harris, A. D., Powell, H., Schaaf, R., Tavassoli, T., & Puts, N. (2022). A Working Taxonomy for Describing the Sensory Differences of Autism. Molecular Autism (in press).; 64.

He, J. L., Wodka, E., Tommerdahl, M., Edden, R. A. E., Mikkelsen, M., Mostofsky, S. H., Puts, N. A. J. (2021) Disorder-specific alterations of tactile sensitivity in neurodevelopmental disorders. Communications Biology, 4(1):97.