MyeSync · The role of PV+ basket cell axon myelination in temporal synchrony of the hippocampal CA2 network
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-03-15 → 2023-03-14
- EU contribution
- €175,572
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
The role of PV+ basket cell axon myelination in temporal synchrony of the hippocampal CA2 network
Neuronal communication takes place at a time scale of milliseconds, which illustrates the importance of neuronal precision and speed for proper brain function. The axon is a subcellular neuronal structure that is responsible for conveying so called action potentials (APs) in a unidirectional manner, from one neuron to the next. To efficiently serve as the highway for inter-neuronal information traffic, axons can be covered up with compact sheaths of myelin. The general belief dominating the field is that the speed benefit provided by myelin is exclusive to long-range neuronal projections of large diameter. Recently though, it has been shown that this “fatty insulator” can be found as well around the relatively short and thin axons of locally projecting parvalbumin positive basket cells (PV+ BCs). This specific class of interneuron provides potent, fast, and ultra-precise perisomatic inhibition onto neighboring excitatory pyramidal cells. By doing so PV+ BCs contribute to the synchronized activity of populations of principal neurons during well-defined brain oscillations. One such type of oscillation they entrain is highly specific to the hippocampus and is called the Sharp Wave Ripple complex (SWRs). It Consists out of sharp waves and high frequency ripples (> 200 Hz), is observed during non-REM sleep, and has been demonstrated to fulfill a pivotal role in memory formation and consolidation. The overarching goal of this MSCA fellowship was to investigate whether myelination of the PV+ BC axon contributes to inhibitory precision within the hippocampus (Objective A) and whether it contributes to fast hippocampal ripple oscillations (Objective B) that are important for mnemonic functions. Loss of myelin within the central nervous system is the underlying cause of Multiple Sclerosis (MS). Besides motor deficits do MS patients often suffer from a decline in memory and reduced cognitive abilities. The exact mechanisms behind this phenomenon remain up to present largely unknown. This fellowship can be expected to give novel insights in the basic principles underlying alterations in the hippocampal circuitry in MS. The aim is to do so by complementing subcellular and synaptic observations with microcircuit measurements and to carefully link structure to cellular function. Such information can be expected to contribute to future translational studies and the development of novel therapies to ultimately try and relieve the suffering of patients living with MS.
Data: CORDIS, © European Union
Project objective
The hippocampus located in the temporal lobe of the brain is of fundamental importance for storage and retrieval of episodic memories. Such brain computations take place at a time scale of milliseconds or less, and rely on neuronal information transfer over subcellular structures which are called axons. Neuronal precision and speed can be achieved by wrapping axons with multi-lamellar membrane sheets of myelin and is of critical importance for proper brain function. Until recently, myelination was thought to be exclusive to long-range excitatory neuronal projections. This view has been drastically revised, and it is now commonly accepted that myelination can be abundant around the axons of local inhibitory interneurons as well. Parvalbumin positive basket cells (PV+ BCs) are fast spiking interneurons which are prominent in the hippocampus where they contribute to the synchrony of action potentials of large populations of neurons. They function as clockworks that drive network oscillations such as sharp wave ripples, are critical for memory consolidation, and are highly abundant in hippocampal area CA2. Whether myelination of the CA2 PV+ BC axon plays a role in their temporally precise inhibitory function, and whether this supports temporally precise neuronal encoding and cognitive performance remains obscure. In this Marie Skłodowska-Curie fellowship, I will address this question by combining my expertise in subcellular patch-clamp methods with the expertise of the host on Ca2+ imaging, myelin physiology, and in vivo electrophysiology. The proposed multimethod and multidisciplinary study will be unique in showing how biophysical changes in small neuronal compartments will lead to alterations of neuronal networks and ultimately to behavioral alterations of the organism. The fellowship is expected to provide me with transferable skills and high throughput techniques that will greatly improve my chances to become an influential leader in the field of neuroscience.
Original text from CORDIS.
Participants
- KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW · AMSTERDAMCoordinatorNetherlands
Links
Data: CORDIS, © European Union