@article {2298, title = {Intestinal transgene delivery with native E.~coli chassis allows persistent physiological changes.}, journal = {Cell}, volume = {185}, year = {2022}, month = {2022 Aug 18}, pages = {3263-3277.e15}, abstract = {

Live bacterial therapeutics (LBTs) could reverse diseases by engrafting in the gut and providing persistent beneficial functions in the host. However, attempts to functionally manipulate the gut microbiome of conventionally raised (CR) hosts have been unsuccessful because engineered microbial organisms (i.e., chassis) have difficulty in colonizing the hostile luminal environment. In this proof-of-concept study, we use native bacteria as chassis for transgene delivery to impact CR host physiology. Native Escherichia coli bacteria isolated from the stool cultures of CR mice were modified to express functional genes. The reintroduction of these strains induces perpetual engraftment in the intestine. In addition, engineered native E.\ coli can induce functional changes that affect physiology of and reverse pathology in CR hosts months after administration. Thus, using native bacteria as chassis to "knock in" specific functions allows mechanistic studies of specific microbial activities in the microbiome of CR hosts and enables LBT with curative intent.

}, keywords = {Animals, Bacteria, Escherichia coli, Gastrointestinal Microbiome, Mice, Microbiota, Transgenes}, issn = {1097-4172}, doi = {10.1016/j.cell.2022.06.050}, author = {Russell, Baylee J and Brown, Steven D and Siguenza, Nicole and Mai, Irene and Saran, Anand R and Lingaraju, Amulya and Maissy, Erica S and Dantas Machado, Ana C and Pinto, Antonio F M and Sanchez, Concepcion and Rossitto, Leigh-Ana and Miyamoto, Yukiko and Richter, R Alexander and Ho, Samuel B and Eckmann, Lars and Hasty, Jeff and Gonzalez, David J and Saghatelian, Alan and Knight, Rob and Zarrinpar, Amir} } @article {1788, title = {Imaging brain activity during complex social behaviors in Drosophila with Flyception2.}, journal = {Nat Commun}, volume = {11}, year = {2020}, month = {2020 01 30}, pages = {623}, abstract = {

Optical in vivo recordings from freely walking Drosophila are currently possible only for limited behaviors. Here, we expand the range of accessible behaviors with a retroreflective marker-based tracking and ratiometric brain imaging system, permitting brain activity imaging even in copulating male flies. We discover that P1 neurons, active during courtship, are inactive during copulation, whereas GABAergic mAL neurons remain active during copulation, suggesting a countervailing role of mAL in opposing P1 activity during mating.

}, keywords = {Animals, Brain, Copulation, Courtship, Drosophila, Drosophila Proteins, Female, GABAergic Neurons, Male, Neuroimaging, Neurons, Olfactory Cortex, Sexual Behavior, Animal, Social Behavior}, issn = {2041-1723}, doi = {10.1038/s41467-020-14487-7}, author = {Grover, Dhruv and Katsuki, Takeo and Li, Jinfang and Dawkins, Thomas J and Greenspan, Ralph J} } @article {1807, title = {Impairments in remote memory caused by the lack of Type 2 IP3 receptors}, journal = {Glia}, volume = {67}, year = {2019}, pages = {1976-1989}, abstract = {

Abstract The second messenger inositol 1,4,5-trisphosphate (IP3) is paramount for signal transduction in biological cells, mediating Ca2+ release from the endoplasmic reticulum. Of the three isoforms of IP3 receptors identified in the nervous system, Type 2 (IP3R2) is the main isoform expressed by astrocytes. The complete lack of IP3R2 in transgenic mice was shown to significantly disrupt Ca2+ signaling in astrocytes, while leaving neuronal intracellular pathways virtually unperturbed. Whether and how this predominantly nonneuronal receptor might affect long-term memory function has been a matter of intense debate. In this work, we found that the absence of IP3R2-mediated signaling did not disrupt normal learning or recent (24{\textendash}48 h) memory. Contrary to expectations, however, mice lacking IP3R2 exhibited remote (2{\textendash}4 weeks) memory deficits. Not only did the lack of IP3R2 impair remote recognition, fear, and spatial memories, but it also prevented naturally occurring post-encoding memory enhancements consequent to memory consolidation. Consistent with the key role played by the downscaling of synaptic transmission in memory consolidation, we found that NMDAR-dependent long-term depression was abnormal in ex vivo hippocampal slices acutely prepared from IP3R2-deficient mice, a deficit that could be prevented upon supplementation with D-serine - an NMDA-receptor co-agonist whose synthesis depends upon astrocytes{\textquoteright} activity. Our results reveal that IP3R2 activation, which in the brain is paramount for Ca2+ signaling in astrocytes, but not in neurons, can help shape brain plasticity by enhancing the consolidation of newly acquired information into long-term memories that can guide remote cognitive behaviors.

}, keywords = {astrocyte, Behavior, Ca2+ signaling, long-term memory, synaptic plasticity}, doi = {https://doi.org/10.1002/glia.23679}, url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/glia.23679}, author = {Pinto-Duarte, Ant{\'o}nio and Roberts, Amanda J. and Ouyang, Kunfu and Sejnowski, Terrence J.} } @article {208, title = {Inhibitory motor control based on complex stopping goals relies on the same brain network as simple stopping.}, journal = {Neuroimage}, volume = {103}, year = {2014}, month = {2014 Dec}, pages = {225-34}, abstract = {

Much research has modeled action-stopping using the stop-signal task (SST), in which an impending response has to be stopped when an explicit stop-signal occurs. A limitation of the SST is that real-world action-stopping rarely involves explicit stop-signals. Instead, the stopping-system engages when environmental features match more complex stopping goals. For example, when stepping into the street, one monitors path, velocity, size, and types of objects and only stops if there is a vehicle approaching. Here, we developed a task in which participants compared the visual features of a multidimensional go-stimulus to a complex stopping-template, and stopped their go-response if all features matched the template. We used independent component analysis of EEG data to show that the same motor inhibition brain network that explains action-stopping in the SST also implements motor inhibition in the complex-stopping task. Furthermore, we found that partial feature overlap between go-stimulus and stopping-template led to motor slowing, which also corresponded with greater stopping-network activity. This shows that the same brain system for action-stopping to explicit stop-signals is recruited to slow or stop behavior when stimuli match a complex stopping goal. The results imply a generalizability of the brain{\textquoteright}s network for simple action-stopping to more ecologically valid scenarios.

}, keywords = {Adolescent, Adult, Brain, Brain Mapping, Electroencephalography, Female, Goals, Humans, Inhibition (Psychology), Male, Psychomotor Performance, Reaction Time, Young Adult}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2014.09.048}, author = {Wessel, Jan R and Aron, Adam R} } @article {204, title = {Independence of early speech processing from word meaning.}, journal = {Cereb Cortex}, volume = {23}, year = {2013}, month = {2013 Oct}, pages = {2370-9}, abstract = {

We combined magnetoencephalography (MEG) with magnetic resonance imaging and electrocorticography to separate in anatomy and latency 2 fundamental stages underlying speech comprehension. The first acoustic-phonetic stage is selective for words relative to control stimuli individually matched on acoustic properties. It begins \~{}60 ms after stimulus onset and is localized to middle superior temporal cortex. It was replicated in another experiment, but is strongly dissociated from the response to tones in the same subjects. Within the same task, semantic priming of the same words by a related picture modulates cortical processing in a broader network, but this does not begin until \~{}217 ms. The earlier onset of acoustic-phonetic processing compared with lexico-semantic modulation was significant in each individual subject. The MEG source estimates were confirmed with intracranial local field potential and high gamma power responses acquired in 2 additional subjects performing the same task. These recordings further identified sites within superior temporal cortex that responded only to the acoustic-phonetic contrast at short latencies, or the lexico-semantic at long. The independence of the early acoustic-phonetic response from semantic context suggests a limited role for lexical feedback in early speech perception.

}, keywords = {Adult, Brain, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Magnetoencephalography, Male, Speech Perception, Young Adult}, issn = {1460-2199}, doi = {10.1093/cercor/bhs228}, author = {Travis, Katherine E and Leonard, Matthew K and Chan, Alexander M and Torres, Christina and Sizemore, Marisa L and Qu, Zhe and Eskandar, Emad and Dale, Anders M and Elman, Jeffrey L and Cash, Sydney S and Halgren, Eric} } @article {133, title = {Illumination controls differentiation of dopamine neurons regulating behaviour.}, journal = {Nature}, volume = {456}, year = {2008}, month = {2008 Nov 13}, pages = {195-201}, abstract = {

Specification of the appropriate neurotransmitter is a crucial step in neuronal differentiation because it enables signalling among populations of neurons. Experimental manipulations demonstrate that both autonomous and activity-dependent genetic programs contribute to this process during development, but whether natural environmental stimuli specify transmitter expression in a neuronal population is unknown. We investigated neurons of the ventral suprachiasmatic nucleus that regulate neuroendocrine pituitary function in response to light in teleosts, amphibia and primates. Here we show that altering light exposure, which changes the sensory input to the circuit controlling adaptation of skin pigmentation to background, changes the number of neurons expressing dopamine in larvae of the amphibian Xenopus laevis in a circuit-specific and activity-dependent manner. Neurons newly expressing dopamine then regulate changes in camouflage colouration in response to illumination. Thus, physiological activity alters the numbers of behaviourally relevant amine-transmitter-expressing neurons in the brain at postembryonic stages of development. The results may be pertinent to changes in cognitive states that are regulated by biogenic amines.

}, keywords = {Animals, Behavior, Animal, Cell Count, Cell Differentiation, Chelating Agents, Dopamine, Egtazic Acid, Gene Expression Regulation, Developmental, Larva, Light, Lighting, Melanotrophs, Neurons, Neuropeptide Y, Photic Stimulation, Skin Pigmentation, Sodium Channel Blockers, Suprachiasmatic Nucleus, Tetrodotoxin, Xenopus laevis}, issn = {1476-4687}, doi = {10.1038/nature07569}, author = {Dulcis, Davide and Spitzer, Nicholas C} } @book {157, title = {An Introduction to Nervous Systems}, year = {2007}, publisher = {Cold Spring Harbor Laboratory Press}, organization = {Cold Spring Harbor Laboratory Press}, address = {Cold Spring Harbor, NY}, abstract = {

An Introduction to Nervous Systems presents the principles of neurobiology from an evolutionary perspective{\textemdash}from single{\textendash}celled organisms to complex invertebrates such as flies{\textemdash}and is ideal for use as a supplemental textbook. Greenspan describes the mechanisms that allow behavior to become ever more sophisticated{\textemdash}from simple avoidance behavior of Paramecium through to the complex cognitive behaviors of the honeybee{\textemdash}and shows how these mechanisms produce the increasing neural complexity found in these organisms. The book ends with a discussion of what is universal about nervous systems and what may be required, neurobiologically, to be human. This novel and highly readable presentation of fundamental principles of neurobiology is designed to be accessible to undergraduate and graduate students not already steeped in the subject.

}, isbn = {978-087969821-8 }, url = {http://www.cshlpress.com/default.tpl?action=full\&cart=146982185827182421\&--eqskudatarq=597\&typ=ps\&newtitle=An\%20Introduction\%20to\%20Nervous\%20Systems}, author = {Greenspan, Ralph J} } @article {150, title = {Identification of genes involved in Drosophila melanogaster geotaxis, a complex behavioral trait.}, journal = {Nat Genet}, volume = {31}, year = {2002}, month = {2002 Aug}, pages = {349-53}, abstract = {

Identifying the genes involved in polygenic traits has been difficult. In the 1950s and 1960s, laboratory selection experiments for extreme geotaxic behavior in fruit flies established for the first time that a complex behavioral trait has a genetic basis. But the specific genes responsible for the behavior have never been identified using this classical model. To identify the individual genes involved in geotaxic response, we used cDNA microarrays to identify candidate genes and assessed fly lines mutant in these genes for behavioral confirmation. We have thus determined the identities of several genes that contribute to the complex, polygenic behavior of geotaxis.

}, keywords = {Animals, Animals, Genetically Modified, Behavior, Animal, DNA, Complementary, Drosophila melanogaster, Female, Genetics, Behavioral, Mutation, Oligonucleotide Array Sequence Analysis}, issn = {1061-4036}, doi = {10.1038/ng893}, author = {Toma, Daniel P and White, Kevin P and Hirsch, Jerry and Greenspan, Ralph J} }