Contributions of synaptic filters to models of synaptically stored memory

The question of how neural systems encode memories in one-shot without immediately disrupting previously stored information has puzzled theoretical neuroscientists for years and it is the central topic of this thesis. Previous attempts on this topic, have proposed that synapses probabilistically update in response to plasticity inducing stimuli to effectively delay the degradation of old memories in the face of ongoing memory storage. Indeed, experiments have shown that synapses do not immediately respond to plasticity inducing stimuli, since these must be presented many times before synaptic plasticity is expressed. Such a delay could be due to the stochastic nature of synaptic plasticity or perhaps because induction signals are integrated before overt strength changes occur.The later approach has been previously applied to control fluctuations in neural development by low-pass filtering induction signals before plasticity is expressed. In this thesis we consider memory dynamics in a mathematical model with synapses that integrate plasticity induction signals to a threshold before expressing plasticity. We report novel recall dynamics and considerable improvements in memory lifetimes against a prominent model of synaptically stored memory. With integrating synapses the memory trace initially rises before reaching a maximum and then falls. The memory signal dissociates into separate oblivescence and reminiscence components, with reminiscence initially dominating recall. Furthermore, we find that integrating synapses possess natural timescales that can be used to consider the transition to late-phase plasticity under spaced repetition patterns known to lead to optimal storage conditions. We find that threshold crossing statistics differentiate between massed and spaced memory repetition patterns. However, isolated integrative synapses obtain an insufficient statistical sample to detect the stimulation pattern within a few memory repetitions. We extend the modelto consider the cooperation of well-known intracellular signalling pathways in detecting storage conditions by utilizing the profile of postsynaptic depolarization. We find that neuron wide signalling and local synaptic signals can be combined to detect optimal storage conditions that lead to stable forms of plasticity in a synapse specific manner.These models can be further extended to consider heterosynaptic and neuromodulatory interactions for late-phase plasticity.<br/

Memory stability and synaptic plasticity

Numerous experiments have demonstrated that the activity of neurons can alter the strength of excitatory synapses. This synaptic plasticity is bidirectional and synapses can be strengthened (potentiation) or weakened (depression). Synaptic plasticity offers a mechanism that links the ongoing activity of the brain with persistent physical changes to its structure. For this reason it is widely believed that synaptic plasticity mediates learning and memory. The hypothesis that synapses store memories by modifying their strengths raises an important issue. There should be a balance between the necessity that synapses change frequently, allowing new memories to be stored with high fidelity, and the necessity that synapses retain previously stored information. This is the plasticity stability dilemma. In this thesis the plasticity stability dilemma is studied in the context of the two dominant paradigms of activity dependent synaptic plasticity: Spike timing dependent plasticity (STDP) and long term potentiation and depression (LTP/D). Models of biological synapses are analysed and processes that might ameliorate the plasticity stability dilemma are identified. Two popular existing models of STDP are compared. Through this comparison it is demonstrated that the synaptic weight dynamics of STDP has a large impact upon the retention time of correlation between the weights of a single neuron and a memory. In networks it is shown that lateral inhibition stabilises the synaptic weights and receptive fields. To analyse LTP a novel model of LTP/D is proposed. The model centres on the distinction between early LTP/D, when synaptic modifications are persistent on a short timescale, and late LTP/D when synaptic modifications are persistent on a long timescale. In the context of the hippocampus it is proposed that early LTP/D allows the rapid and continuous storage of short lasting memory traces over a long lasting trace established with late LTP/D. It is shown that this might confer a longer memory retention time than in a system with only one phase of LTP/D. Experimental predictions about the dynamics of amnesia based upon this model are proposed. Synaptic tagging is a phenomenon whereby early LTP can be converted into late LTP, by subsequent induction of late LTP in a separate but nearby input. Synaptic tagging is incorporated into the LTP/D framework. Using this model it is demonstrated that synaptic tagging could lead to the conversion of a short lasting memory trace into a longer lasting trace. It is proposed that this allows the rescue of memory traces that were initially destined for complete decay. When combined with early and late LTP/D iii synaptic tagging might allow the management of hippocampal memory traces, such that not all memories must be stored on the longest, most stable late phase timescale. This lessens the plasticity stability dilemma in the hippocampus, where it has been hypothesised that memory traces must be frequently and vividly formed, but that not all traces demand eventual consolidation at the systems level

Single Molecule Fluorescence Spectroscopy and Imaging: Advanced Methods and Applications in Life Sciences

The visualization of biological structures down to the molecular length scale has been recently made possible by the development of super-resolution fluorescence microscopy. These techniques now routinely resolve biological structures down to a few nanometers. Various super-resolution techniques have been developed, the most successful being Stimulated Depletion Emission (STED) microscopy and Single Molecule Localization Microscopy (SMLM). In what follows, I will focus on the latter class of techniques which is based on the fact that a single molecule image allows for localizing the molecule with a much higher accuracy than the diffraction limit of resolution of the used microscope. However, a big challenge of SMLM is to achieve a similar super-resolution along the optical axis of a microscope. For this purpose, metal-induced energy transfer (MIET) imaging was recently introduced as an elegant method for axially localizing fluorophores with nanometer precision. The underlying principle of MIET is based on an electromagnetic near-field-mediated energy transfer from an excited fluorescent emitter (donor) to a thin planar metal film (acceptor). This energy transfer leads to a distance-dependent modulation of an emitter’s fluorescence lifetime (quenching), that can be easily measured with conventional fluorescence lifetime measurement techniques. The power of MIET is that it works with any fluorophore, and it only requires a conventional fluorescence lifetime imaging (FLIM) microscope. In this thesis, I present a powerful modification and further development of MIET, that is called graphene-induced energy transfer (GIET). GIET replaces the metal film of MIET with a single sheet of graphene which reduces the quenching range by one order of magnitude, leading to a tenfold improvement in axial resolution. This enables the localization of fluorophores with sub-nanometer accuracy. We demonstrate the potential of GIET by quantifying inter-leaflet distances in supported lipid bilayers (SLBs) and discuss the potential of the technique particularly in membrane biophysics applications. The second line of this thesis is devoted to the complementary topic of fast molecular dynamics. While super-resolution microscopy succeeds in resolving structural details with nanometer resolution, it is too slow for temporally resolving the fast dynamics of the observed molecules. For this purpose, spectroscopic techniques such as single molecule fluorescence spectroscopy (SMFS) have become an important tool that can resolve molecular dynamics down to timescales of nanoseconds. In my thesis, I focus on fluorescence lifetime correlation spectroscopy (FLCS), an advanced variant of fluorescence correlation spectroscopy (FCS). Using FLCS, I could disentangle two emission states in an autofluorescent protein that have otherwise highly overlapping spectra, and I could quantify the microsecond switching rates between these two states. As compared to other existing methods, FLCS offers the unique advantage of probing such fast switching kinetics with nanosecond temporal resolution under equilibrium conditions at room temperature, making it the method of choice for similar studies of complex luminescent emitters. Finally, I will also present another study where I utilized advanced FCS for studying protein self-assembly. In summary, my thesis presents several advanced methods in SMLM and SMFS which significantly enhance the spatial and temporal resolution at the single molecule level. I believe that the presented methods will find a wide range of applications in the life sciences.2021-06-0

Annual Report 2020 - Institute of Ion Beam Physics and Materials Research

As for everybody else also for the Institute of Ion Beam Physics and Materials Research (IIM), the COVID-19 pandemic overshadowed the usual scientific life in 2020. Starting in March, home office became the preferred working environment and the typical institute life was disrupted. After a little relaxation during summer and early fall, the situation became again more serious and in early December we had to severely restrict laboratory activities and the user operation of the Ion Beam Center (IBC). For the most part of 2020, user visits were impossible and the services delivered had to be performed hands-off. This led to a significant additional work load on the IBC staff. Thank you very much for your commitment during this difficult period. By now user operation has restarted, but we are still far from business as usual. Most lessons learnt deal with video conference systems, and everybody now has extensive experience in skype, teams, webex, zoom, or any other solution available. Conferences were cancelled, workshops postponed, and seminar or colloquia talks delivered online. Since experimental work was also impeded, maybe 2020 was a good year for writing publications and applying for external funding. In total, 204 articles have been published with an average impact factor of about 7.0, which both mark an all-time high for the Institute. 13 publications from last year are highlighted in this Annual Report to illustrate the wide scientific spectrum of our institute. In addition, 20 new projects funded by EU, DFG, BMWi/AiF and SAB with a total budget of about 5.7 M€ have started. Thank you very much for making this possible. Also, in 2020 there have been a few personalia to be reported. Prof. Dr. Sibylle Gemming has left the HZDR and accepted a professor position at TU Chemnitz. Congratulations! The hence vacant position as the head of department was taken over by PD Dr. Artur Erbe by Oct. 1st. Simultaneously, the department has been renamed to “Nanoelectronics”. Dr. Alina Deac has left the institute in order to dedicate herself to new opportunities at the Dresden High Magnetic Field Laboratory. Dr. Matthias Posselt went to retirement after 36 years at the institute. We thank Matthias for his engagement and wish him all the best for the upcoming period of his life. However, also new equipment has been setup and new laboratories founded. A new 100 kV accelerator is integrated into our low energy ion nanoengineering facility and complements our ion beam technology in the lower energy regime. This setup is particularly suited to perform ion implantation into 2D materials and medium energy ion scattering (MEIS). Finally, we would like to cordially thank all partners, friends, and organizations who supported our progress in 2020. First and foremost we thank the Executive Board of the Helmholtz-Zentrum Dresden-Rossendorf, the Minister of Science and Arts of the Free State of Saxony, and the Ministers of Education and Research, and of Economic Affairs and Energy of the Federal Government of Germany. Many partners from univer¬sities, industry and research institutes all around the world contributed essentially, and play a crucial role for the further development of the institute. Last but not least, the directors would like to thank all members of our institute for their efforts in these very special times and excellent contributions in 2020

Environmental Health

Environmental health practitioners worldwide are frequently presented with issues that require further investigating and acting upon so that exposed populations can be protected from ill-health consequences. These environmental factors can be broadly classified according to their relation to air, water or food contamination. However, there are also work-related, occupational health exposures that need to be considered as a subset of this dynamic academic field. This book presents a review of the current practice and emerging research in the three broadly defined domains, but also provides reference for new emerging technologies, health effects associated with particular exposures and environmental justice issues. The contributing authors themselves display a range of backgrounds and they present a developing as well as a developed world perspective. This book will assist environmental health professionals to develop best practice protocols for monitoring a range of environmental exposure scenarios

Molecular Imaging

The present book gives an exceptional overview of molecular imaging. Practical approach represents the red thread through the whole book, covering at the same time detailed background information that goes very deep into molecular as well as cellular level. Ideas how molecular imaging will develop in the near future present a special delicacy. This should be of special interest as the contributors are members of leading research groups from all over the world