On January 19 - 20th, 2017, a highly interdisciplinary audience from physics, life sciences and medicine gathered at the newly opened Max-Planck-Institute for the Science of Light in Erlangen to listen attentively to a series of inspiring lectures on recent developments and future pro­spects in Systems Neuroscience. The presentations were given by a group of dedicated young scientists who promise to become, or already are, young leaders in the field. All of them have already made major contributions to fundamental issues in systems neuroscience, such as the principles of information processing, the underpinnings of cognitive functions and affective states, and the mechanisms that disrupt normal circuit operations in neuropsychiatric diseases. Befitting the futuristic spell which emanates from the superb architecture of the meeting site, the speakers all placed particular emphasis on technology-driven ap­proaches in their research. Their presentations underscored that high-end electrophysiological and optical methods are indispensable prerequisites to unravel the functional connectivity and the networks dynamics in the normal and diseased brain.

January 19th

Warm and instructive Welcome Addresses were delivered by Prof. Vahid Sandoghdar, Director at the Max-Planck-Institute for the Science of Light and host of this meeting, and by Prof. Jürgen Schüttler, Dean of the Medical Faculty of the Friedrich-Alexander-Universität Erlangen-Nürnberg. They both set the stage for this symposium and put it in context with the local efforts to identify emerging areas for highly interdisciplinary endeavors between the Max-Planck-Institute for the Science of Light, the newly established Zentrum für Physik und Medizin, and the Institute of Physiology and Pathophysiology of the University.

Dr. Anna Beyeler from the Massachusetts Institute of Technology (Cambridge, USA) opened the scientific sessions with a lecture entitled Functional Connectivity of Amygdala Neural Populations Encoding Emotional Memories. She combined behavioral studies, optogenetics and advanced in vivo and ex vivo electrophysiology to understand valence encoding in the amygdala, a brain region essential for regulating emotions and affective behavior. The amygdala is part of a complex neuronal network whose dysfunction has been implicated in anxiety, depression, addiction and obsessive-compulsive disorders. Dr. Beyeler explained how the amygdala assigns a positive or negative value to a perception that becomes stored in memory and how the processing of the attributed valence during memory retrieval determines subsequent behavior.

Dr. Torfi Sigurdsson from the Institute of Neurophysiology of the University of Frankfurt (Germany) continued with a lecture on "Neuronal Network Dysfunction in Psychiatric Disease: Insights from Animal Models". He used transgenic mice which over-express the dopamine D2 receptor as an animal model of schizophrenia. Advanced electrophysiological and computational methods allowed him to study the synchronization of electrical activity between different brain regions while they engage in a cognitive task. He focused on synchronous 4 Hz oscillations between the prefrontal cortex (PFC) and the ventral tegmental area (VTA) which are known to coordinate neuronal activity during cognitive performance. Combining behavioral experiments with parallel recordings from PFC and VTA, he found a characteristic desynchronization of 4 Hz oscillations in the transgenic mice which would account for their behavioral deficits in a working memory task.

The morning session was completed by Dr. Wolfgang Kelsch from the Zentralinstitut für Seelische Gesundheit (Mannheim, Germany) and the University of Heidelberg, whose talk was entitled "Oxytocin Enhances Social Recognition by Modulating Cortical Control of Early Sensory Processing". Oxytocin is known to promote the social interaction and recognition of conspecifics in an olfaction-dependent fashion. To elucidate the neuronal underpinnings of the social effects of oxytocin, Dr. Kelsch used behavioral analyses in conjunction with optogenetically evoked oxytocin release and region-specific deletion of oxytocin receptors as well as in vivo and ex vivo electrophysiology from the anterior olfactory cortex and the olfactory bulb under optogenetic control. His research revealed an oxytocin-mediated top-down control of sensory processing in the olfactory bulb that, by improving signal-to-noise in odor coding, proves essential for appropriate social perception and behaviors.

The afternoon session began with a presentation by Dr. Julia Schiemann from the Centre for Integrative Physiology of the University of Edinburgh (UK), who talked on "Noradrenergic Control of Skilled Motor Movements". In previous work, she had already advanced noradrenaline as an important neuromodulator in the cortex for precise motor control. To study how noradrenaline improves motor coordination at the cellular level, she developed a refined motor task and employed optogenetic, imaging and electrophysiological techniques. This allowed her to record the activity of cortical neurons in the primary motor cortex while the mouse made a skilled movement. Moreover, she determined how the optogenetic activation or silencing of noradrenergic projections to the motor cortex shaped the firing patterns of the cortical neurons and altered the performance of the mice in the concomitant motor task.

The second (and last) speaker in the afternoon was Dr. Jose Guzmán from the Institute of Science and Technology (Klosterneuburg, Austria) whose lecture was entitled "The Functional Microcircuit of Pattern Completion in the Hippocampal CA3 Network". Within the hippocampal circuit, different regions have been assigned distinct roles in the encoding and retrieval of memories. For example, the CA3 region of the hippocampus is endowed with an autoassociative network that allows for the recall of memory contents from partial or noisy cues, a process called pattern completion. Dr. Guzmán has now identified the synaptic mechanisms that underlie this important cognitive operation. Simultaneous recordings from eight CA3 neurons in the hippocampal slice preparation served to identify the prevailing motifs of synaptic connectivity in CA3 networks, which were mostly disynaptic in nature. When these motifs were implemented in real-size computational models of the CA3 region, they emerged as essential features to generate pattern completion.

A lecture on how "Surface Dynamics of Ion Channels Tune Neuronal Communication" by Dr. Martin Heine from the Leibniz-Institut für Neurobiology (Magdeburg, Germany) started off the second day of the symposium. He argued that even minimal lateral movements of ion channels that play key roles in transmitter release and postsynaptic responses will have considerable impact on the strength of synaptic transmission. In order to follow the fluctuations of presynaptic voltage-gated Ca2+ channels and postsynaptic ionotropic glutamate receptors on the nanometer scale, he used super-resolution microscopy and assessed the functional consequences of the observed ion channel displacements by combining single particle tracking with patch-clamp recordings and optical read-outs of neuronal activity. Most importantly, he was able to demonstrate that an experimental immobilization of the fraction of highly mobile ion channels altered essential features of synaptic transmission including short-term plasticity.

The next presentation was given by Prof. Dr. Benjamin Grewe from the Institute of Neuroinformatics (ETH Zürich, Switzerland). He talked about "Embedding Associative Memories in Neuronal Networks of the Emotional Brain". Combining auditory fear conditioning, an established model of associative learning, with simultaneous recordings of the activity of 150 – 200 neurons in the amygdala of mice by means of a miniature, head-mounted fluorescence microscope, he gained new insights into the mechanism that links a conditioned stimulus (CS) to an unconditioned stimulus (US). In contrast to the widely-held view that the learned CS-US association results from a Hebbian, i.e. synaptic plasticity-dependent mechanism, he obtained evidence that fear learning coincides with a shift of the neuronal ensemble encoding CS towards the ensemble encoding US. Thus, the two neuronal populations encoding either CS or US, which were initially non-overlapping, became more congruent as the association between the stimuli was established.

Carsten Tischbirek from the Institute of Neuroscience of the Technical University (München, Germany) then gave a presentation on "Two-Photon Calcium-Imaging of Neuronal Circuits in all Layers of the Mouse Cortex in vivo". Imaging of cytosolic Ca2+ transients by two-photon laser scanning microscopy has become a valuable tool to interrogate neuronal activity in the brain of living animals at scales ranging from subcellular compartments such as dendritic spines up to large neuronal populations of entire networks. So far, however, imaging of cortical activity at single-cell resolution was largely restricted to the upper layers of the mouse neocortex, thus precluding a comprehensive capture of electrical activity in basic cortical processing modules such as columns or barrels. Carsten Tischbirek showed that with the use of the red-shifted fluorescent Ca2+ indicator Cal-590 it is now possible to analyze the response properties of tone-sensitive neurons through the entire depth of the primary auditory cortex.

The final lecture entitled "Probing Synaptic Interactions during Sensory Processing in Deep Brain Structures" was given by Dr. Alexander Groh from the Department of Neurosurgery of the Klinikum Rechts der Isar (Technical University, München, Germany). The thalamus is widely regarded as a centrally positioned gate that controls the input pathways to the cortex, but the cortex sends also projections to the thalamus which are thought to modulate thalamic activity in a top-down fashion. Dr. Groh employed deep brain electrophysiological techniques to record from thalamic neurons while activating corticothalamic projections by optogenetic stimulation in mouse barrel cortex. His findings demonstrate that sensory processing relies on a strongly reciprocal interplay between thalamus and cortex.

The symposium was concluded by Prof. Dr. Sandoghdar, who extended his gratitude to the speakers for rendering a fascinating overview on research projects at the forefront of Systems Neuroscience, with each lecture giving rise to lively and often far-ranging discussions with the audience. In his understanding, the symposium also called upon physics to assume a primary role in devising new means of insight into the workings of the brain at all levels of investigation.

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