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Trial Lecture – time and place
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Adjudication committee
- First opponent: Group Leader Motoharu Yoshida, Leibniz Institute for Neurobiology (LIN) and German Center for Neurodegenerative Diseases (DZNE), Germany
- Second opponent: Group Leader, Director of Research Desdemona Fricker, Université de Paris, France
- Third member and chair of the evaluation committee: Professor Erik Taubøll, University of Oslo
Chair of the Defence
Professor emeritus Terje Lømo, University of Oslo
Principal Supervisor
Professor Johan Frederik Storm, University of Oslo
Summary
Action potentials are the primary mechanism of signalling between neurons in the brain, and are usually initiated by incoming synaptic inputs, producing the characteristic “spike” which forms the basis of neurotransmission.
Neuromodulation and excitatory synaptic input can generate a form of action potential bursts which greatly outlast the input signal that generated them, known as plateau potentials (PPs), where persistent depolarisation and spiking that can persist for several seconds after the offset of the initiatory signal.
Such prolonged and intense activity imposes the output of the bursting cell on the neuronal network, potentially altering the functional processing of the network. As such PPs have been shown to have great importance in controlling motor activity, and in the mammalian cortex, have an important role in both working memory by allowing signals to persist in neuronal networks, as well as promote encoding of memories by stimulating long-term potentiation of synapses.
The aim of this thesis is to describe PPs and their mechanisms of induction in different neuron types throughout the rodent brain, their dependence on different neuromodulators and sensitivity to general anaesthesia.
First, we investigated PPs in genetically identified interneurons in the mouse hippocampus, their induction by glutamatergic and cholinergic neuromodulators, mechanisms underlying the plateaus, and the synergy between modulatory systems which serve to greatly enhance the bursting output of these cells.
Next, we studied cholinergic PP mechanisms in layer 2/3 pyramidal cells in the prefrontal cortex (PFC). We determined that, unlike in other cells, PPs are mediated not by voltage gated calcium channels, but are mediated by TRP channels, specifically TRPC4 &5. We also found that PPs are generated in the soma/basal dendrites as they were inducible after the apical dendrite had been cut away from the cell body.
Finally, we investigated the sensitivity of the previously studied cholinergic PPs in PFC L2/3PCs to general anaesthetic agents ketamine and propofol. PPs were inhibited by clinically-relevant concentrations of both anaesthetics suggesting that PPs have a role in supporting the conscious processes that anaesthesia inhibits.
This thesis provides further insight into the generation and mechanisms behind the conserved electrophysiological features of PPs across different neuron types and brain regions.
Additional information
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