Neurofly 2008 abstracts : the 12th European Drosophila neurobiology conference 6-10 September 2008 Wuerzburg, Germany

This volume consists of a collection of conference abstracts

Assessing Neuronal Synchrony and Brain Function Through Local Field Potential and Spike Analysis

Studies of neuronal network oscillations and rhythmic neuronal synchronization have led to a number of important insights in recent years, giving us a better understanding of the temporal organization of neuronal activity related to essential brain functions like sensory processing and cognition. Important principles and theories have emerged from these findings, including the communication through coherence hypothesis, which proposes that synchronous oscillations render neuronal communication effective, selective, and precise. The implications of such a theory may be universal for brain function, as the determinants of neuronal communication inextricably shape the neuronal representation of information in the brain. However, the study of communication through coherence is still relatively young. Since its articulation in 2005, the theory has predominantly been applied to assess cortical function and its communication with downstream targets in different sensory and behavioral conditions. The results herein are intended to bolster this hypothesis and explore new ways in which oscillations coordinate neuronal communication in distributed regions. This includes the development of new analytic tools for interpreting electrophysiological patterns, inspired by phase synchronization and spike train analysis. These tools aim to offer fast results with clear statistical and physiological interpretation

The spatio-temporal segregation of GAD forms defines distinct GABA signaling functions in the developing mouse olfactory system and provides novel insights into the origin and migration of GnRH neurons.

GABA (gamma-aminobutyric acid) has a dual role as an inhibitory neurotransmitter in the adult central nervous system (CNS) and as a signaling molecule exerting largely excitatory actions during development. The rate-limiting step of GABA synthesis is catalyzed by two glutamic acid decarboxylase isoforms GAD65 and GAD67 co-expressed in the GABAergic neurons of the CNS. Here we report that the two GADs show virtually non-overlapping expression patterns consistent with distinct roles in the developing peripheral olfactory system. GAD65 is expressed exclusively in undifferentiated neuronal progenitors confined to the proliferative zones of the sensory vomeronasal and olfactory epithelia. In contrast GAD67 is expressed in a subregion of the non-sensory epithelium/vomeronasal organ epithelium containing the putative GnRH progenitors and GnRH neurons migrating from this region through the frontonasal mesenchyme (FNM) into the basal forebrain. Only GAD67+, but not GAD65+ cells accumulate detectable GABA. We further demonstrate that GAD67 and its embryonic splice variant EGAD concomitant with GnRH are dynamically regulated during GnRH neuronal migration in vivo and in two immortalized cell lines representing migratory (GN11) and post-migratory (GT1-7) stage GnRH neurons, respectively. Analysis of GAD65/67 single and double knock-out (KO) embryos revealed that the two GADs play complementary (inhibitory) roles in GnRH migration ultimately modulating the speed and/or direction of GnRH migration. Our results also suggest that GAD65 and GAD67/EGAD characterized by distinct subcellular localization and kinetics have disparate functions during olfactory system development mediating proliferative and migratory responses putatively through specific subcellular GABA pools. (c) 2014 Wiley Periodicals, Inc. Develop Neurobiol, 2014

Novel measure of olfactory bulb function in health and disease

Present neuroimaging techniques are capable of recording the neural activity from all over the brain but the olfactory bulb (OB). The OB is the first olfactory processing stage of the central nervous system and the site of insult in several neurological disorders, particularly Parkinson’s disease (PD). It has been suggested that the OB has a pivotal role in the olfactory system anal-ogous to primary visual cortex (V1) and thalamus in the visual system. However, due to the existing technical limitations, there has not been any non-invasive technique that can reliably measure the OB function in humans, consequently limiting its functional recording to one in-tracranial study dating back to the 60s. Initially in Study I, a non-invasive method of measuring the function of human OB is devel-oped, so-called electrobulbogram (EBG). In line with previous animal literature as well as the only intracranial study in human OB, it was demonstrated that gamma oscillations on the EBG electrodes occurred shortly after the odor onset. Subsequently, applying source recon-struction analysis provided evidence that observed oscillations were localized to the OB. Ad-ditionally, the OB recording with the EBG method showed a test-retest reliability comparable with visual event related potentials. Notably, the detected gamma oscillations were demon-strated to be insensitive to habituation, the OB’s marked characteristic which has previously been demonstrated in rodents. Last, but not least, assessing the EBG response in an individual who did not have the bilateral OB indicated that the lack of OB results in disappearance of gamma oscillations in the EBG electrodes. Given that Study I determined the possibility of reliably measuring the function of the OB using the EBG, in Study II, I assessed the functional role of OB’s oscillations in the pro-cessing of the odor valence. Odor valence has been suggested to be linked to approach–avoidance responses and therefore, processing of odor valence is thought to be one of the core aspects of odor processing in the olfactory system. Consequently, using combined EBG and EEG recording, OB activity was reconstructed on the source level during processing of odors with different valences. Gamma and beta oscillations were found to be related to va-lence perception in the human OB. Moreover, the early beta oscillations were associated with negative but not positive odors, where these beta oscillations can be linked to preparatory neural responses in the motor cortex. Subsequently, in a separate experiment, negative odors were demonstrated to trigger a whole-body motor avoidance response in the time window overlapping with the valence processes in the OB. These negative odor-elicited motor re-sponses were measured by a force plate as a leaning backward motion. Altogether, the results from Study II indicated that the human OB processes odor valence sequentially in the gamma and beta frequency bands, where the early processing of negative odors in the OB might be facilitating rapid approach-avoidance behaviors. To further evaluate the functional role of the OB in odor processing, in Study III, OB’s communication with its immediate recipient, namely piriform cortex (PC), was assessed. These two areas are critical nodes of the olfactory system which communicate with each other through neural oscillations. The activity of the OB and the PC were reconstructed using a combination of EBG, EEG, and source reconstruction techniques. Subsequently, the cross spectrogram of the OB and the PC was assessed as a measure of functional connectivity where temporal evolution from fast to slow oscillations in the OB–PC connectivity was found during the one second odor processing. Furthermore, the spectrally resolved Granger causal-ity analysis suggested that the afferent connection form the OB to the PC occurred in the gamma and beta bands whereas the efferent connection from the PC to the OB was concen-trated in the theta and delta bands. Notably, odor identity could be deciphered from the low gamma oscillatory pattern in the OB–PC connectivity as early as 100ms after the odor onset. Hence, findings from this study elucidate on our understanding of the bidirectional infor-mation flow in the human olfactory system. Olfactory dysfunction, due to neurodegeneration in the OB, commonly appears several years earlier than the occurrence of the PD-related characteristic motor symptoms. Consequently, a functional measure of the OB may serve as a potential early biomarker of PD. In Study IV, OB function was assessed in PD to answer whether the EBG method can be used to dissociate individuals with a PD diagnosis from healthy age-matched controls. The spectrogram of the EBG signals indicated that there were different values in gamma, beta, and theta for PDs compared with healthy controls. Specifically, six components were found in the EBG re-sponse during early and late time points which together dissociate PDs from controls with a 90% sensitivity and a 100% specificity. Furthermore, these components were linked to med-ication, disease duration and severity, as well as clinical odor identification performance. Overall, these findings support the notion that EBG has a diagnostic value and can be further developed to serve as an early biomarker for PD. In the last study, Study V, the prevalence of COVID-19 was determined using odor intensity ratings as an indication of olfactory dysfunction. Using a large sample data (n = 2440) from a Swedish population, odor intensity ratings of common household items over time were found to be closely associated with prevalence prediction of COVID-19 in the Stockholm region over the same time-period (r = -.83). Impairment in odor intensity rating was further correlated with the number of reported COVID-19 symptoms. Relatedly, individuals who progressed from having no symptoms to having at least one symptom had a marked decline in their odor intensity ratings. The results from this study, given the relatively large sample size, provided a concrete basis for the future studies to further assess the potential association between the deficits in the OB function and olfactory dysfunction in COVID-19. In conclusion, our proposed method for non-invasive measurement of the OB function was shown to provide a reliable recording with a potential as a diagnostic tool for PD. Combining EBG and EEG allowed for reconstruction of the OB signal at the source level, where specific oscillations were found to be critical for odor valence processing and rapid avoidance re-sponse. Moreover, oscillations in different frequency bands were found to be critical for the OB reciprocal communications and transfer of odor identity information to higher order ol-factory subsystems. Finally, COVID-19 was found to be associated with a decline in olfactory acuity which might originate from damage to the patient’s OB. In conclusion, the results from the studies within this thesis provide a new perspective on the functional role of oscillations in the human OB

Ca2+-sensors and ROS-GC: interlocked sensory transduction elements: a review

From its initial discovery that ROS-GC membrane guanylate cyclase is a mono-modal Ca2+-transduction system linked exclusively with the photo-transduction machinery to the successive finding that it embodies a remarkable bimodal Ca2+ signaling device, its widened transduction role in the general signaling mechanisms of the sensory neuron cells was envisioned. A theoretical concept was proposed where Ca2+-modulates ROS-GC through its generated cyclic GMP via a nearby cyclic nucleotide gated channel and creates a hyper- or depolarized sate in the neuron membrane (Ca2+ Binding Proteins 1:1, 7–11, 2006). The generated electric potential then becomes a mode of transmission of the parent [Ca2+]i signal. Ca2+ and ROS-GC are interlocked messengers in multiple sensory transduction mechanisms. This comprehensive review discusses the developmental stages to the present status of this concept and demonstrates how neuronal Ca2+-sensor (NCS) proteins are the interconnected elements of this elegant ROS-GC transduction system. The focus is on the dynamism of the structural composition of this system, and how it accommodates selectivity and elasticity for the Ca2+ signals to perform multiple tasks linked with the SENSES of vision, smell, and possibly of taste and the pineal gland. An intriguing illustration is provided for the Ca2+ sensor GCAP1 which displays its remarkable ability for its flexibility in function from being a photoreceptor sensor to an odorant receptor sensor. In doing so it reverses its function from an inhibitor of ROS-GC to the stimulator of ONE-GC membrane guanylate cyclase

High-frequency neural oscillations and visual processing deficits in schizophrenia

Visual information is fundamental to how we understand our environment, make predictions, and interact with others. Recent research has underscored the importance of visuo-perceptual dysfunctions for cognitive deficits and pathophysiological processes in schizophrenia. In the current paper, we review evidence for the relevance of high frequency (beta/gamma) oscillations towards visuo-perceptual dysfunctions in schizophrenia. In the first part of the paper, we examine the relationship between beta/gamma band oscillations and visual processing during normal brain functioning. We then summarize EEG/MEG-studies which demonstrate reduced amplitude and synchrony of high-frequency activity during visual stimulation in schizophrenia. In the final part of the paper, we identify neurobiological correlates as well as offer perspectives for future research to stimulate further inquiry into the role of high-frequency oscillations in visual processing impairments in the disorder

Precise temporal regulation of alternative splicing during neural development

Alternative splicing (AS) is one crucial step of gene expression that must be tightly regulated during neurodevelopment. However, the precise timing of developmental splicing switches and the underlying regulatory mechanisms are poorly understood. Here we systematically analyze the temporal regulation of AS in a large number of transcriptome profiles of developing mouse cortices, in vivo purified neuronal subtypes, and neurons differentiated in vitro. Our analysis reveals early-switch and late-switch exons in genes with distinct functions, and these switches accurately define neuronal maturation stages. Integrative modeling suggests that these switches are under direct and combinatorial regulation by distinct sets of neuronal RNA-binding proteins including Nova, Rbfox, Mbnl, and Ptbp. Surprisingly, various neuronal subtypes in the sensory systems lack Nova and/or Rbfox expression. These neurons retain the “immature” splicing program in early-switch exons, affecting numerous synaptic genes. These results provide new insights into the organization and regulation of the neurodevelopmental transcriptome

Texture dependence of motion sensing and free flight behavior in blowflies

Lindemann JP, Egelhaaf M. Texture dependence of motion sensing and free flight behavior in blowflies. Frontiers in Behavioral Neuroscience. 2013;6:92.Many flying insects exhibit an active flight and gaze strategy: purely translational flight segments alternate with quick turns called saccades. To generate such a saccadic flight pattern, the animals decide the timing, direction, and amplitude of the next saccade during the previous translatory intersaccadic interval. The information underlying these decisions is assumed to be extracted from the retinal image displacements (optic flow), which scale with the distance to objects during the intersaccadic flight phases. In an earlier study we proposed a saccade-generation mechanism based on the responses of large-field motion-sensitive neurons. In closed-loop simulations we achieved collision avoidance behavior in a limited set of environments but observed collisions in others. Here we show by open-loop simulations that the cause of this observation is the known texture-dependence of elementary motion detection in flies, reflected also in the responses of large-field neurons as used in our model. We verified by electrophysiological experiments that this result is not an artifact of the sensory model. Already subtle changes in the texture may lead to qualitative differences in the responses of both our model cells and their biological counterparts in the fly's brain. Nonetheless, free flight behavior of blowflies is only moderately affected by such texture changes. This divergent texture dependence of motion-sensitive neurons and behavioral performance suggests either mechanisms that compensate for the texture dependence of the visual motion pathway at the level of the circuits generating the saccadic turn decisions or the involvement of a hypothetical parallel pathway in saccadic control that provides the information for collision avoidance independent of the textural properties of the environment

Developmental and interspecies comparison of morphology and plasticity in neuronal circuits involved in olfactory information processing

The anterior piriform cortex (aPCx) is a three layered paleocortex receiving afferent inputs from the olfactory bulb as well as local and long-range associational inputs. Neurons in layer 2 are segregated into layer 2A and layer 2B according to their position, morphology and implementation in the sensory and associative circuits. The dendritic architecture of these neurons is determined during postnatal development and plays an important role for the functionality and circuit integration of the two cell types. Here, confocal imaging, electrophysiology, morphometry and Ca2+ imaging, were combined in order to study the development of the dendritic arborizations for both subtypes of layer 2 neurons. Three different growth phases were identified: branch complexity determination, branch elongation and pruning, occurring at different time windows during development. Layer 2A and layer 2B neurons showed morphological differences between their apical and basal dendrites from the very first postnatal days; as well as phase-specific differences during development associated to differences in circuit implementation. During the first postnatal week, early spontaneous network activity in layer 2 of the aPCx displayed differences between layer 2A and layer 2B neurons in their functional connectivity, reflected in the morphological dissimilarities between their basal dendritic trees during the period of branch complexity determination. Additionally, strong differences in growth phase three were observed. Pruning was exclusive for layer 2B neurons and selective for apical dendrites receiving layer 1A sensory inputs. These differences between layer 2A and layer 2B cells in their morphological and functional development exhibit the close association between circuit specificity and neuronal development. Finally, synaptic plasticity in the mossy fiber (MF) pathway of the hippocampus in shrews was investigated and compared to mice. Although hippocampal structure in shrews is preserved, short and long-term plasticity at the MF synapsis was lower compared to mice, suggesting different involvement of these synapses in the behavioral outcome of different species.Der Cortex piriformis anterior (aPCx auf Englisch) ist ein dreischichtiger Paläokortex, der sensorische afferente Eingänge aus dem Riechkolben sowie intracerebrale assoziative Eingänge empfängt. Die Neuronen in Schicht 2 werden nach ihrer Position, Morphologie und Einbindung in die sensorischen und rekurrenten Netzwerke in die Schichten 2A und 2B unterteilt. Die dendritische Architektur dieser Neurone wird während der postnatalen Entwicklung festgelegt und spielt eine wichtige Rolle für die Funktionalität und Netzwerkintegration der beiden Zelltypen. Hier wurden konfokales Imaging, Elektrophysiologie, Morphometrie und Kalzium-Imaging kombiniert, um die Entwicklung der Dendritenbäume für beide Subtypen von Schicht-2-Neuronen zu untersuchen. Es wurden drei verschiedene Wachstumsphasen identifiziert: Bestimmung der Komplexität der Verzweigung, Verlängerung der Verzweigung und strukturelle Vereinfachung, die in verschiedenen Zeitfenstern während der Entwicklung auftreten. Neurone der Schicht 2A und der Schicht 2B zeigten bereits in den ersten postnatalen Tagen morphologische Unterschiede zwischen ihren apikalen und basalen Dendriten sowie phasenspezifische Unterschiede während der Entwicklung, die mit Unterschieden in der Netzwerkimplementierung verbunden sind. Während der ersten postnatalen Woche zeigte die frühe spontane Netzwerkaktivität in Schicht 2 des aPCx Unterschiede in der funktionellen Konnektivität zwischen Neuronen der Schicht 2A und Schicht 2B, die sich in den morphologischen Unterschieden zwischen ihren basalen Dendritenbäumen während der Bestimmung der Verzweigungskomplexität widerspiegelten. Außerdem wurden starke Unterschiede in der dritten Wachstumsphase beobachtet. Die strukturelle Vereinfachung fand ausschließlich bei Neuronen der Schicht 2B statt und war selektiv für apikale Dendriten, die sensorische Inputs der Schicht 1A erhielten. Diese Unterschiede zwischen Zellen der Schicht 2A und der Schicht 2B in ihrer morphologischen und funktionellen Entwicklung zeigen den engen Zusammenhang zwischen Netzwerkspezifität und neuronaler Entwicklung. Schließlich wurde die synaptische Plastizität des Moosfaser (MF)-Trakts des Hippocampus bei Spitzmäusen untersucht und mit der von Mäusen verglichen. Obwohl die Struktur des Hippocampus bei Spitzmäusen erhalten ist, war die Kurz- und Langzeitplastizität an den MF-Synapsen im Vergleich zu Mäusen geringer, was auf eine unterschiedliche Beteiligung dieser Synapsen an spezifisch adaptierte Verhaltensweisen der beiden Spezies hindeutet

Neurochemistry

Neurochemistry is a flourishing academic field that contributes to our understanding of molecular, cellular and medical neurobiology. As a scientific discipline, neurochemistry studies the role of chemicals that build the nervous system, it explores the function of neurons and glial cells in health and disease, it discovers aspects of cell metabolism and neurotransmission, and it reveals how degenerative processes are at work in the nervous system. Accordingly, this book contains chapters from a variety of topics that fall into the following broad sections: I. Neural Membranes and Intracellular Signaling, II. Neural Processing and Intercellular Signaling, III. Growth, Development and Differentiation, and IV. Neurodegenerative Diseases. The book presents comprehensive reviews in these different areas written by experts in their respective fields. Neurodegeneration and neuronal diseases are featured prominently and are a recurring theme throughout most chapters. This book will be a most valuable resource for neurochemists and other scientists alike. In addition, it will contribute to the training of current and future neurochemists and, hopefully, will lead us on the path to curing some of the biggest challenges in human health