“The development of neuronal circuits in the cerebral cortex during embryonic and postnatal development is a complex process, and abnormalities are known to lead to developmental disorders,” says Teppola-Gürel.
“Spontaneously occurring network bursts are widely observed during the functional maturation of developing neocortical networks in both sensory cortices in vivo and dissociated cortical cultures in vitro. These network bursts occur at the same time with the formation of the neuronal network structure and synaptic transmission. By uncovering the synaptic mechanisms that contribute to neuronal network activity during early development, we can potentially find ways to prevent neurodevelopmental disorders in the future”, she says.
In her doctoral dissertation, Teppola-Gürel investigated how excitatory and inhibitory receptors affect the initiation, propagation and termination of network bursts. She found that the AMPA receptors with excitatory effects mediate fast excitatory synaptic transmission, whereas the slow NMDA receptors maintain the existing network-wide burst activity.
In addition, Teppola-Gürel examined how the fast, inhibitory GABAA receptors contribute to the network-wide activity mediated by the excitatory AMPA and NMDA receptors. What she discovered was a novel pattern of interplay between the fast AMPA receptor-mediated activity and the GABAA receptor-mediated inhibition, indicating that an imbalance between excitatory and inhibitory receptors leads to so-called superbursts, which are associated with epileptic seizures. Her findings suggest that an imbalance between excitatory and inhibitory receptors diminishes the efficiency of processing incoming sensory information in the cerebral cortex, which, in turn, can lead to a variety of neurological disorders.
“My dissertation demonstrates for the first time how multi-unit time series data recorded from cortical networks can be utilised to support the development of spiking network models. Data-driven computational models can be used to simulate the impact of drugs on network burst activity and possibly even predict the onset of neurodevelopmental disorders,” Teppola-Gürel points out.
Teppola-Gürel also studied the ability of human neuroblastoma cells to differentiate into neuronal phenotypes with the help of estradiol, cholesterol, a brain-derived neurotrophic factor and retinoid acid. The results demonstrate that human neuroblastoma cells can be differentiated into neuronal phenotypes. The research results show that the combined effects of estradiol, cholesterol and retinoid acid promote the growth and branching of neurites, synaptic vesicles and the neuronal network in in vitro human cell cultures. The differentiation method developed by Teppola-Gürel will support further studies on human cells.
Heidi Teppola-Gürel was born in Oulu, Finland, and graduated from the upper secondary school of Oulu University Teacher Training School in 2002. She received her MSc degree from the Institute of Medical Technology at the then University of Tampere in 2008. Teppola-Gürel continued her studies towards a doctoral degree at Tampere University’s Faculty of Medicine and Health Technology and at the University of Freiburg, Germany. She is currently working as a researcher in the Neuroscience Center at the University of Helsinki.
The doctoral dissertation of MSc Heidi Teppola-Gürel in the field of neuroscience titled Rodent and Human Neuronal Networks – Analysis of Functional Maturation, Synaptic Transmission, and Spontaneous Activity in Vitro will be publicly examined in the Faculty of Medicine and Health Technology at Tampere University on Friday 22 April 2022, starting at 12 noon. The venue will be the auditorium S2 in the Sähkötalo building, address: Korkeakoulunkatu 3. The opponent will be Professor Maria Victoria Sanchez-Vives from the University of Barcelona while Docent Marja-Leena Linne will act as the custos.
The dissertation is available online at
https://urn.fi/URN:ISBN:978-952-03-2346-2