Cerebellar impact on developing thalamo-cortical networks in health and disease
Cerebellar impact on developing thalamo-cortical networks in health and disease
From foetal stages the cerebellum and cerebrum are connected in both directions and proper functioning of both structures and connections is critical for normal behavior and well-being. Aberrant cerebello-cerebral connections results in impaired motor, sensory, social, cognitive and/or executive behavior.
It is our goal to increase our fundamental knowledge of the formation and maturation of the synaptic connections that moderate cerebellar interactions with thalamo-cortical networks. (fig. 1). Hereby we aim to improve the bed-to-bench translation of experimental therapies that can cure the consequences of adverse early life events.
Using whole-cell patch clamp recordings with optogenetic and chemogenetic tools and post-hoc anatomical reconstructions we investigate the local and regional connections within and between cerebellar and cerebral structures (fig. 2 – a schematic abstract of current research proposal and techniques). We link neuronal activity patterns to motor, sensory, social and cognitive behaviors, allowing us to increase our understanding of the biological principles underlying the development of cerebro-cerebellar connections.
Our research line provides valuable information that aid to tune diagnostics in the neonatal intensive care unit (fig. 3 – tractography of developing pathways between cerebellum, thalamus and cerebral cortex). Prof. Benders, chief neonatologist of the national expertise center for neonatal neurology, and several senior staff members (e.g. Dr. Jeroen Dudink, Dr. Maria-Luisa Tataranno, Dr. Niek van der Aa, Dr. Floris Groenendaal) are closely involved in the design of specific research questions that are currently answered using rodent models.
Key publications uitklapper, klik om te openen
- Dumas DB, Gornati SV, Adolfs Y, Shimogori T, Pasterkamp RJ, Hoebeek FE. Anatomical development of the cerebellothalamic tract in embryonic mice. Cells. 2022, 11(23):3800.
- Eelkman Rooda OHJ, Kros L, Faneyte SJ, Holland PJ, Gornati SV, Poelman HJ, Jansen NA, Tolner EA, van den Maagdenberg AMJM, De Zeeuw CI, Hoebeek FE. Single-pulse stimulation of cerebellar nuclei stops epileptic thalamic activity. Brain Stim. 2021, 14(4):861-872.
- Annink KV, Meerts L, van der Aa NE, Alderliesten T, Nikkels PGJ, Nijboer CHA, Groenendaal F, de Vries LS, Benders MJNL, Hoebeek FE, Dudink J. Cerebellar injury in term neonates with hypoxic-ischemic encephalopathy is underestimated. Pediatric Res. 2021, 89(5):1171-1178.
- Gornati SV, Schaefer CB, Eelkman Rooda OHJ, Nigg A, De Zeeuw CI, Hoebeek FE. Differentiation of cerebellar impact on thalamic nuclei. Cell rep. 2018, 23(9):2690-2704.
- Pieterman K, Batalle D, Dudink J, Tournier, JD, Hughes EJ, Barnett ML, Benders M, Edwards AD, Hoebeek FE, Counsell SJ. Cerebello-cerebral connectivity in the developing brain. Brain Structure and Function. 2017, 222:1625-1634.
- Dudink J. (2021) Cerebellar injury in term neonates with hypoxic-ischemic encephalopathy is underestimated. (2021) Pediatric Res 89(5):1171-1178.
Funding and Grants uitklapper, klik om te openen
- ZonMW Meer Kennis Minder Dieren (#114.024.177; 2022): Systematic review to explore optimal rodent model for neonatal epilepsy model
- NWO-Gravitation (#024.005.022; 2022): Dutch Brain Initiative 2 - Closed-loop Neuromonitoring and Neurostimulation in neonatal rodents
- Dr. CJ Vaillant fund (2018): Equipment for in vivo Neuromonitoring system
- NWO VIDI (#016.121.346; 2012): Unravelling the cerebellar impact on thalamo-cortical networks
- NWO-TOP cross discipline (#1350186; 2010): Multidisciplinary studies on Cerebellum, ataxia, epilepsy and migraine
- NWO VENI (#863.08.015); 2008): Plasticity of excitatory and inhibitory synapses in cerebellar cortex
- Erasmus University Fellowship (2006): Calcium channelopathies and their impact on cerebellar activity
Contact uitklapper, klik om te openen
PI: Freek Hoebeek, personal profile page
Email: f.e.hoebeek@umcutrecht.nl