Franck PolleuxSwammerdam lecture
The Neuroscience Symposia are organized weekly by the Netherlands Institute for Neuroscience. The presentations are given by researchers from the institute or by guest speakers. The title and content of the symposium is usually made known in the week prior to the presentation.
You will receive an invitation for the online symposium in your email.
Guest speaker Christian Lohmann
4 pm – A human-specific modifier of synaptic development, cortical circuit connectivity and function
The remarkable cognitive abilities characterizing humans has been linked to unique patterns of connectivity characterizing the neocortex. Comparative studies have shown that human cortical pyramidal neurons (PN) receive a significant increase of synaptic inputs when compared to other mammals, including non-human primates and rodents, but how this may relate to changes in cortical connectivity and function remains largely unknown. We previously identified a human-specific gene duplication (HSGD), SRGAP2C, that, when induced in mouse cortical PNs drives human-specific features of synaptic development, including a correlated increase in excitatory (E) and inhibitory (I) synapse density (Charrier et al. Cell 2012; Fossatti et al. Neuron 2016). However, the origin and nature of this increased connectivity and its impact on cortical circuit function was unknown. I will present new results exploring these questions (see https://www.biorxiv.org/content/10.1101/852970v1). Using a combination of transgenic approaches and quantitative monosynaptic tracing, we demonstrate that humanization of SRGAP2C expression in the mouse cortex leads to a specific increase in local and long-range cortico-cortical inputs received by layer 2/3 cortical PNs. Moreover, using in vivo 2-photon imaging in the barrel cortex of awake mice, we show that humanization of SRGAP2C expression increases the reliability and selectivity of sensory-evoked responses in layer 2/3 PNs. Our results suggest that the emergence of SRGAP2C during human evolution underlie a new substrate for human brain evolution whereby it led to increased local and long-range cortico-cortical connectivity and improved reliability of sensory-evoked cortical coding.
Charrier, C. et al. Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation. Cell 149, 923–35 (2012).
Fossati, M. et al. SRGAP2 and Its Human-Specific Paralog Co-Regulate the Development of Excitatory and Inhibitory Synapses. Neuron 91, 356–369 (2016).