PhD defence C.B. (Carmen) Schäfer

This dissertation focuses on describing the anatomical and functional characteristics of selected pathways that wire the cerebellum, the thalamus, the sensory cortex and the motor cortex. We zoom in on individual hot spots of synaptic connectivity and describe the anatomical and physiological characteristics that shape the function of the pathway in the bigger network of hardwired brain routes. In Chapter 2 we describe the physiological properties of cortical driver synapses in sensory thalamus and characterize their properties in absence of the presynaptic scaffolding protein Bassoon. In Chapter 3 we evaluate the convergence pattern of primary sensory cortex and the cerebellar output nuclei in extra-thalamic areas. In Chapter 4, we describe the cerebellar input in the individual motor thalamic nuclei. Chapter 5 shows that the in Chapter 4 described cerebellar input converges with modulatory feedback from motor cortical layer 6 in ventro-lateral nucleus. Furthermore, we show that the thalamo-cortical spike transfer can be facilitated by both pauses in cerebellar activation as well as via the inputs from motor cortex. In Chapter 6, we describe how hyperactivity of the mTOR signaling pathway, due to a dominant-active mutation in the RHEB1 gene induces enhanced axonal connectivity and hyperexcitability of distally connected neurons. In Chapter 7 we focus on the communication between the cortex and the cerebellum and characterize a novel subpopulation of corticospinal neuron in the motor cortex that forms a direct connection to the cerebellar nuclei.

The public defence will take place at the Prof. Andries Queridoroom, 3rd floor Education Center, Erasmus MC. The ceremony will begin exactly at 10.30 AM. In light of the solemn nature of the ceremony, we recommend that you do not take children under the age of 6 to the first part of the ceremony.