Draft:Corette Wierenga

Corette Wierenga (born in 1972, in The Netherlands) is a neuroscientist with a physics background working at the Donders Institute for Brain, Cognition and Behaviour. She explores the molecular mechanisms underlying the formation, removal and plasticity of inhibitory synapses. In her lab, she combines advanced two-photon microscopy and single cell electrophysiology in mouse brain slices, using molecular biology techniques to label specific cells or proteins. Wierenga has been appointed as a full professor in neurophysiology at Radboud University since September 2022.

Education and early life
Wierenga completed a MSc in Theoretical Physics at the Vrije Universiteit, in Amsterdam in 1996. In 2002 she obtained a PhD in Neurobiology at Universiteit van Amsterdam under the supervision of Prof. Dr. W.J. Wadman. In her thesis titled "Functional interaction between interneurons and the pyramidal cell population in the hippocampal CA1 area", she studied how inhibitory neurons shape the activity in the hippocampal CA1 network in epilepsy and during normal activation. She found that the excitatory inputs towards feedforward and feedback interneurons display distinctive short-term plasticity, effectively changing the network architecture of the hippocampal CA1 region in a frequency-dependent manner by coupling and uncoupling different inhibitory inputs.

Career and research
After completing her PhD, Wierenga was a postdoctoral fellow in the group of Prof. Gina Turrigiano at Brandeis University in Waltham (Massachusetts, USA). Here she made an important contribution to a long-standing debate about the locus of homeostatic plasticity. She showed that young neurons show a purely postsynaptic expression mechanism of activity-dependent scaling of excitatory synapses. As the neurons within the network mature, postsynaptic homeostatic scaling is accompanied by additional presynaptic changes. These findings suggest that the expression mechanism of homeostatic plasticity can be tailored to the developmental stage of the network. It also illustrates that multiple forms of plasticity often co-occur in neuronal circuits.

Between 2005 and 2011, Wierenga was a senior postdoc in the group of Prof. Tobias Bonhoeffer at the Max Planck Institute of Neurobiology in Martinsried-Munich, Germany. During this time, Wierenga discovered that the formation of inhibitory synapses is fundamentally different from excitatory synapses. At inhibitory synapses, the presynaptic axon plays a central role during synapse formation and plasticity. Calcium imaging in dendrites revealed the high temporal and spatial impact of individual inhibitory synapses in shaping local calcium signals in dendrites, emphasising that the precise dendritic location of an inhibitory synapse determines its potential impact on nearby excitatory synapses.

After her postdoctoral work, in 2012 she started her independent research group at Utrecht University. Her lab has developed a highly sensitive method to monitor and analyse inhibitory synapse dynamics using two-photon microscopy in living brain slices. These live imaging experiments revealed that inhibitory synapses are highly dynamic structures and that their dynamics are regulated by ongoing activity and molecular signals in the local neuronal network. The Wierenga lab established that the formation of inhibitory synapses is a highly regulated, multistep process and has already identified signalling pathways regulating specific steps, including an increase in cAMP/PKA signalling (via G-protein coupled receptor activation) to trigger the initial formation of boutons and Sema4D/PlexinB1 signalling for subsequent activity-dependent stabilisation. In addition, the Wierenga lab discovered a local feedback system that assures local inhibitory control over clusters of excitatory synapses within the dendrites. Two-photon glutamate uncaging and time-lapse imaging revealed that clustered activity of excitatory synapses can induce local synthesis of endocannabinoids in the dendrite, and this endocannabinoid signalling can trigger the formation of a new inhibitory synapse at that dendritic location. The precise alignment of excitatory and inhibitory synapses within dendrites is thought to be crucial to allow context-dependent gating of information.

In 2022, Wierenga joined the Donders Institute for Brain, Cognition and Behaviour at Radboud University, where she works in the "Development and lifelong plasticity" and "Natural Computing & Neurotechnology" research themes, more specifically, in the field of synaptic physiology. Her research focuses on inhibitory synapses on a molecular, cellular, and network scale. Wierenga uses the insights from fundamental neuroscience to help disentangle underlying disease mechanisms and generate new ideas for therapeutic targets. For instance, she recently showed how inhibitory synapses are dysregulated by amyloid β oligomers and potentially contribute to the network hyperexcitability that is prominent at early stages of Alzheimer's disease. She also assesses postnatal development of inhibitory synapses during normal or disturbed brain development to improve our understanding of neurodevelopmental disorders.

Teaching
Wierenga was appointed as a full professor of Neurophysiology at Radboud University on September 2022. As such, she is the coordinator of the "Neurons and Synapses" course given at the university, which is aimed for second-year biology students keen on neurosciences.

Public engagement
Wierenga has been involved in the divulgation of neuroscience on a series of platforms which are accessible to anyone. Some of the topics include neurogenetics or animal research:


 * Interview at Utrecht University "What's best for a baby's brain" (June 2022)
 * Interview at RTV Utrecht "Vraag van de Stad: is muzikaliteit genetisch bepaald?", in English "Question from the City: is musicality genetically determined?" (February 2022)
 * Interview at AD "Tussen leven en dood", in English "Between life and death" (November 2021)
 * Interview at de Volskrant "Opinie: Zonder proefdieren hadden we nu geen vaccin tegen het coronavirus", in English "Opinion: Without laboratory animals we would not have a vaccine against the coronavirus" (January 2021)
 * Podcast episode "The Unfinished Brain" (May 2020)
 * Interview at Utrecht University "Worden je hersenen steeds slimmer?", in English "Is your brain getting smarter?" (2019)

Awards and grants
Wierenga has been the recipient of several grants and awards:


 * 2022 NWO ENW-M grant - Inhibitory synapse formation and removal: a central role for axonal cAMP and PKA signalling
 * 2022-2026 Alzheimer Nederland grant "Investigating effects of Aβ oligomers on presynaptic nanostructure and function"
 * 2020-2024 NWO-ENW klein-I grant "How do dendrites coordinate adjacent excitatory and inhibitory inputs?"
 * 2019-2021 Alzheimer Nederland grant "Linking amyloid β-induced microglia activation and network hyperexcitability"
 * 2017-2022 FOM program "NeuroPhotonics: unravelling the physics of signalling in intact neuronal networks"
 * 2017-2019 Alzheimer Nederland grant "Amyloid β-induced pathology of inhibitory synapses"
 * 2016-2021 ALW grant (with Louk Vanderschuren) "How early social experience shapes higher brain function"
 * 2015-2019 FOM grant "Two-photon microscopy of nonlinearities in dendritic computation"
 * 2014-2015 Dynamics of Youth Seeding grant (with Louk Vanderschuren) "How early social experience shapes brain development"
 * 2012-2017 VIDI grant from the Dutch Scientific Organization (NWO) "Balancing the Brain: Local Interactions between Excitatory and Inhibitory Synapses"
 * 2008 UNESCO-L'Oréal award "For Women in Science" Germany National award (in Germany) for excellent and promising young female scientists in natural sciences

Books

 * Hoogenraad CC, Wierenga C (2014) Neurons, Overview. In: Aminoff M.J. and Daroff R.B. (eds.) Encyclopedia of the Neurological Sciences, 2nd edition, vol. 3, pp. 456-458. Oxford: Academic Press