ABSTRACT
Variability is a prominent feature of behavior and is an active element of certain behavioral strategies. To understand how neuronal circuits control variability, we examined the propagation of sensory information in a chemotaxis circuit of C. elegans where discrete sensory inputs can drive a probabilistic behavioral response. Olfactory neurons respond to odor stimuli with rapid and reliable changes in activity, but downstream AIB interneurons respond with a probabilistic delay. The interneuron response to odor depends on the collective activity of multiple neurons-AIB, RIM, and AVA-when the odor stimulus arrives. Certain activity states of the network correlate with reliable responses to odor stimuli. Artificially generating these activity states by modifying neuronal activity increases the reliability of odor responses in interneurons and the reliability of the behavioral response to odor. The integration of sensory information with network states may represent a general mechanism for generating variability in behavior.
Subject(s)
Caenorhabditis elegans/physiology , Olfactory Pathways , Animals , Behavior, Animal , Calcium Signaling , Neurons/metabolism , OdorantsABSTRACT
Humans have been trying to understand animal behavior at least since recorded history. Recent rapid development of new technologies has allowed us to make significant progress in understanding the physiological and molecular mechanisms underlying behavior, a key goal of neuroethology. However, there is a tradeoff when studying animal behavior and its underlying biological mechanisms: common behavior protocols in the laboratory are designed to be replicable and controlled, but they often fail to encompass the variability and breadth of natural behavior. This Commentary proposes a framework of 10 key questions that aim to guide researchers in incorporating a rich natural context into their experimental design or in choosing a new animal study system. The 10 questions cover overarching experimental considerations that can provide a template for interspecies comparisons, enable us to develop studies in new model organisms and unlock new experiments in our quest to understand behavior.
Subject(s)
Behavior, Animal , Animals , Behavior, Animal/physiologyABSTRACT
Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly. Canonical disease models suggest that defective interactions between complement factor H (CFH) and cell surface heparan sulfate (HS) result in increased alternative complement pathway activity, cytolytic damage, and tissue inflammation in the retina. Although these factors are thought to contribute to increased disease risk, multiple studies indicate that noncanonical mechanisms that result from defective CFH and HS interaction may contribute to the progression of AMD as well. A total of 60 ciliated sensory neurons in the nematode Caenorhabditis elegans detect chemical, olfactory, mechanical, and thermal cues in the environment. Here, we find that a C. elegans CFH homolog localizes on CEP mechanosensory neuron cilia where it has noncanonical roles in maintaining inversin/NPHP-2 within its namesake proximal compartment and preventing inversin/NPHP-2 accumulation in distal cilia compartments in aging adults. CFH localization and maintenance of inversin/NPHP-2 compartment integrity depend on the HS 3-O sulfotransferase HST-3.1 and the transmembrane proteoglycan syndecan/SDN-1. Defective inversin/NPHP-2 localization in mouse and human photoreceptors with CFH mutations indicates that these functions and interactions may be conserved in vertebrate sensory neurons, suggesting that previously unappreciated defects in cilia structure may contribute to the progressive photoreceptor dysfunction associated with CFH loss-of-function mutations in some AMD patients.
Subject(s)
Complement Factor H/metabolism , Heparitin Sulfate/metabolism , Retina/metabolism , Animals , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/metabolism , Cilia/metabolism , Complement Factor H/physiology , Heparitin Sulfate/physiology , Macular Degeneration/metabolism , Macular Degeneration/physiopathology , Neurons/metabolism , Transcription Factors/metabolismABSTRACT
Recent progress in neuroscience has been facilitated by tools for neuronal activation and inactivation that are orthogonal to endogenous signaling systems. We describe here a chemical-genetic approach for inducible silencing of Caenorhabditis elegans neurons in intact animals, using the histamine-gated chloride channel HisCl1 from Drosophila and exogenous histamine. Administering histamine to freely moving C. elegans that express HisCl1 transgenes in neurons leads to rapid and potent inhibition of neural activity within minutes, as assessed by behavior, functional calcium imaging, and electrophysiology of neurons expressing HisCl1. C. elegans does not use histamine as an endogenous neurotransmitter, and exogenous histamine has little apparent effect on wild-type C. elegans behavior. HisCl1-histamine silencing of sensory neurons, interneurons, and motor neurons leads to behavioral effects matching their known functions. In addition, the HisCl1-histamine system can be used to titrate the level of neural activity, revealing quantitative relationships between neural activity and behavioral output. We use these methods to dissect escape circuits, define interneurons that regulate locomotion speed (AVA, AIB) and escape-related omega turns (AIB), and demonstrate graded control of reversal length by AVA interneurons and DA/VA motor neurons. The histamine-HisCl1 system is effective, robust, compatible with standard behavioral assays, and easily combined with optogenetic tools, properties that should make it a useful addition to C. elegans neurotechnology.
Subject(s)
Caenorhabditis elegans/metabolism , Chloride Channels/metabolism , Drosophila Proteins/metabolism , Histamine/pharmacology , Neurons/metabolism , Animals , Animals, Genetically Modified , Caenorhabditis elegans/genetics , Chloride Channels/antagonists & inhibitors , Drosophila , Drosophila Proteins/antagonists & inhibitors , Microfluidic Analytical Techniques , Models, Neurological , Motor Activity/drug effects , Neurons/drug effects , Patch-Clamp TechniquesABSTRACT
We describe an intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) with signal-to-noise ratio and kinetics appropriate for in vivo imaging. We engineered iGluSnFR in vitro to maximize its fluorescence change, and we validated its utility for visualizing glutamate release by neurons and astrocytes in increasingly intact neurological systems. In hippocampal culture, iGluSnFR detected single field stimulus-evoked glutamate release events. In pyramidal neurons in acute brain slices, glutamate uncaging at single spines showed that iGluSnFR responds robustly and specifically to glutamate in situ, and responses correlate with voltage changes. In mouse retina, iGluSnFR-expressing neurons showed intact light-evoked excitatory currents, and the sensor revealed tonic glutamate signaling in response to light stimuli. In worms, glutamate signals preceded and predicted postsynaptic calcium transients. In zebrafish, iGluSnFR revealed spatial organization of direction-selective synaptic activity in the optic tectum. Finally, in mouse forelimb motor cortex, iGluSnFR expression in layer V pyramidal neurons revealed task-dependent single-spine activity during running.
Subject(s)
Escherichia coli Proteins , Fluorescent Dyes , Glutamic Acid/metabolism , Green Fluorescent Proteins , Recombinant Fusion Proteins , Synaptic Transmission/physiology , Animals , Astrocytes/metabolism , Biosensing Techniques , Caenorhabditis elegans , Calcium Signaling/physiology , Escherichia coli Proteins/chemical synthesis , Excitatory Postsynaptic Potentials/physiology , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/metabolism , Green Fluorescent Proteins/chemical synthesis , Hippocampus/metabolism , Mice , Motor Cortex/metabolism , Neurons/metabolism , Photic Stimulation , Pyramidal Cells/metabolism , Recombinant Fusion Proteins/chemical synthesis , Retina/physiology , Signal-To-Noise Ratio , ZebrafishABSTRACT
Mutation and overexpression of receptor tyrosine kinases or the proteins they regulate serve as oncogenic drivers in diverse cancers. To better understand receptor tyrosine kinase signaling and its link to oncogenesis, we used protein microarrays to systematically and quantitatively measure interactions between virtually every SH2 or PTB domain encoded in the human genome and all known sites of tyrosine phosphorylation on 40 receptor tyrosine kinases and on most of the SH2 and PTB domain-containing adaptor proteins. We found that adaptor proteins, like RTKs, have many high affinity bindings sites for other adaptor proteins. In addition, proteins that drive cancer, including both receptors and adaptor proteins, tend to be much more highly interconnected via networks of SH2 and PTB domain-mediated interactions than nononcogenic proteins. Our results suggest that network topological properties such as connectivity can be used to prioritize new drug targets in this well-studied family of signaling proteins.
Subject(s)
Carcinogenesis/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Phosphotyrosine/metabolism , HEK293 Cells , Humans , Oncogene Proteins/metabolism , Protein Binding , Protein Interaction Domains and Motifs , Protein Interaction Maps , Receptor Protein-Tyrosine Kinases/metabolism , Signal TransductionABSTRACT
Genetically encoded calcium indicators (GECIs) are powerful tools for systems neuroscience. Recent efforts in protein engineering have significantly increased the performance of GECIs. The state-of-the art single-wavelength GECI, GCaMP3, has been deployed in a number of model organisms and can reliably detect three or more action potentials in short bursts in several systems in vivo. Through protein structure determination, targeted mutagenesis, high-throughput screening, and a battery of in vitro assays, we have increased the dynamic range of GCaMP3 by severalfold, creating a family of "GCaMP5" sensors. We tested GCaMP5s in several systems: cultured neurons and astrocytes, mouse retina, and in vivo in Caenorhabditis chemosensory neurons, Drosophila larval neuromuscular junction and adult antennal lobe, zebrafish retina and tectum, and mouse visual cortex. Signal-to-noise ratio was improved by at least 2- to 3-fold. In the visual cortex, two GCaMP5 variants detected twice as many visual stimulus-responsive cells as GCaMP3. By combining in vivo imaging with electrophysiology we show that GCaMP5 fluorescence provides a more reliable measure of neuronal activity than its predecessor GCaMP3. GCaMP5 allows more sensitive detection of neural activity in vivo and may find widespread applications for cellular imaging in general.
Subject(s)
Calcium Signaling , Fluorescent Dyes/chemistry , Fluorometry/methods , Green Fluorescent Proteins/chemistry , Neuroimaging/methods , Neurons/chemistry , Peptides/chemistry , Synaptic Transmission , Animals , Astrocytes/chemistry , Astrocytes/ultrastructure , Caenorhabditis elegans , Crystallography, X-Ray , Drosophila melanogaster/growth & development , Female , Fluorescent Dyes/analysis , Genes, Synthetic , Genetic Vectors , Green Fluorescent Proteins/analysis , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/isolation & purification , HEK293 Cells/chemistry , HEK293 Cells/ultrastructure , Hippocampus/chemistry , Hippocampus/cytology , Humans , Larva , Lasers , Mice , Models, Molecular , Mutagenesis, Site-Directed , Neuromuscular Junction/chemistry , Neuromuscular Junction/ultrastructure , Neurons/physiology , Neurons/ultrastructure , Neuropil/chemistry , Neuropil/physiology , Neuropil/ultrastructure , Olfactory Receptor Neurons/chemistry , Olfactory Receptor Neurons/physiology , Olfactory Receptor Neurons/ultrastructure , Peptides/analysis , Peptides/genetics , Photic Stimulation , Protein Conformation , Rats , Recombinant Fusion Proteins/analysis , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Retinal Bipolar Cells/chemistry , Retinal Bipolar Cells/physiology , Retinal Bipolar Cells/ultrastructure , Zebrafish/growth & developmentABSTRACT
Abrupt changes in behavior can often be associated with changes in underlying behavioral states. When placed off food, the foraging behavior of C. elegans can be described as a change between an initial local-search behavior characterized by a high rate of reorientations, followed by a global-search behavior characterized by sparse reorientations. This is commonly observed in individual worms, but when numerous worms are characterized, only about half appear to exhibit this behavior. We propose an alternative model that predicts both abrupt and continuous changes to reorientation that does not rely on behavioral states. This model is inspired by molecular dynamics modeling that defines the foraging reorientation rate as a decaying parameter. By stochastically sampling from the probability distribution defined by this rate, both abrupt and gradual changes to reorientation rates can occur, matching experimentally observed results. Crucially, this model does not depend on behavioral states or information accumulation. Even though abrupt behavioral changes do occur, they may not necessarily be indicative of abrupt changes in behavioral states, especially when abrupt changes are not universally observed in the population.
ABSTRACT
The African malaria mosquito Anopheles gambiae exhibits a strong innate drive to seek out humans in its sensory environment, classically entering homes to land on human skin in the hours flanking midnight. To gain insight into the role that olfactory cues emanating from the human body play in generating this epidemiologically important behavior, we developed a large-scale multi-choice preference assay in Zambia with infrared motion vision under semi-field conditions. We determined that An. gambiae prefers to land on arrayed visual targets warmed to human skin temperature during the nighttime when they are baited with carbon dioxide (CO2) emissions reflective of a large human over background air, body odor from one human over CO2, and the scent of one sleeping human over another. Applying integrative whole body volatilomics to multiple humans tested simultaneously in competition in a six-choice assay, we reveal high attractiveness is associated with whole body odor profiles from humans with increased relative abundances of the volatile carboxylic acids butyric acid, isobutryic acid, and isovaleric acid, and the skin microbe-generated methyl ketone acetoin. Conversely, those least preferred had whole body odor that was depleted of carboxylic acids among other compounds and enriched with the monoterpenoid eucalyptol. Across expansive spatial scales, heated targets without CO2 or whole body odor were minimally or not attractive at all to An. gambiae. These results indicate that human scent acts critically to guide thermotaxis and host selection by this prolific malaria vector as it navigates towards humans, yielding intrinsic heterogeneity in human biting risk.
Subject(s)
Anopheles , Malaria , Taxis Response , Animals , Humans , Odorants , Body Odor , Carbon Dioxide , Mosquito Vectors , Pheromones, Human , Carboxylic AcidsABSTRACT
Although epidermal growth factor receptor (EGFR; also called ErbB1) and its relatives initiate one of the most well-studied signalling networks, there is not yet a genome-wide view of even the earliest step in this pathway: recruitment of proteins to the activated receptors. Here we use protein microarrays comprising virtually every Src homology 2 (SH2) and phosphotyrosine binding (PTB) domain encoded in the human genome to measure the equilibrium dissociation constant of each domain for 61 peptides representing physiological sites of tyrosine phosphorylation on the four ErbB receptors. This involved 77,592 independent biochemical measurements and provided a quantitative protein interaction network that reveals many new interactions, including ones that fall outside of our current view of domain selectivity. By slicing through the network at different affinity thresholds, we found surprising differences between the receptors. Most notably, EGFR and ErbB2 become markedly more promiscuous as the threshold is lowered, whereas ErbB3 does not. Because EGFR and ErbB2 are overexpressed in many human cancers, our results suggest that the extent to which promiscuity changes with protein concentration may contribute to the oncogenic potential of receptor tyrosine kinases, and perhaps other signalling proteins as well.
Subject(s)
ErbB Receptors/chemistry , ErbB Receptors/metabolism , Protein Array Analysis , Cell Line , Computational Biology , Genomics , Humans , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Phosphopeptides/chemistry , Phosphopeptides/metabolism , Phosphorylation , Phosphotyrosine/metabolism , Protein Binding , Protein Structure, Tertiary , Software , Surface Plasmon Resonance , src Homology DomainsABSTRACT
Quantitative behavioral analysis of Drosophila courtship reveals that visual cues of a female's body influence which actions a male performs during courtship. These actions in turn influence female actions, producing a mutual synchronization of courtship between male and female flies.
Subject(s)
Cues , Sexual Behavior, Animal , Animals , Courtship , Drosophila , Female , Male , Social BehaviorABSTRACT
A hallmark of adaptive behavior is the ability to flexibly respond to sensory cues. To understand how neural circuits implement this flexibility, it is critical to resolve how a static anatomical connectome can be modulated such that functional connectivity in the network can be dynamically regulated. Here, we review recent work in the roundworm Caenorhabditis elegans on this topic. EM studies have mapped anatomical connectomes of many C. elegans animals, highlighting the level of stereotypy in the anatomical network. Brain-wide calcium imaging and studies of specified neural circuits have uncovered striking flexibility in the functional coupling of neurons. The coupling between neurons is controlled by neuromodulators that act over long timescales. This gives rise to persistent behavioral states that animals switch between, allowing them to generate adaptive behavioral responses across environmental conditions. Thus, the dynamic coupling of neurons enables multiple behavioral states to be encoded in a physically stereotyped connectome.
Subject(s)
Connectome , Animals , Brain/physiology , Caenorhabditis elegans/physiology , Neurons/physiology , Neurotransmitter AgentsABSTRACT
The orb web is a remarkable example of animal architecture that is observed in families of spiders that diverged over 200 million years ago. While several genomes exist for araneid orb-weavers, none exist for other orb-weaving families, hampering efforts to investigate the genetic basis of this complex behavior. Here we present a chromosome-level genome assembly for the cribellate orb-weaving spider Uloborus diversus. The assembly reinforces evidence of an ancient arachnid genome duplication and identifies complete open reading frames for every class of spidroin gene, which encode the proteins that are the key structural components of spider silks. We identified the 2 X chromosomes for U. diversus and identify candidate sex-determining loci. This chromosome-level assembly will be a valuable resource for evolutionary research into the origins of orb-weaving, spidroin evolution, chromosomal rearrangement, and chromosomal sex determination in spiders.
Subject(s)
Fibroins , Spiders , Animals , Phylogeny , Fibroins/genetics , Silk/genetics , Genome , Sex Chromosomes/genetics , Spiders/geneticsABSTRACT
A survey was initiated to determine the prevalence of Salmonella enterica in the environment in and around Monterey County, CA, a major agriculture region of the United States. Trypticase soy broth enrichment cultures of samples of soil/sediment (n = 617), water (n = 252), wildlife (n = 476), cattle feces (n = 795), and preharvest lettuce and spinach (n = 261) tested originally for the presence of pathogenic Escherichia coli were kept in frozen storage and later used to test for the presence of S. enterica. A multipathogen oligonucleotide microarray was employed to identify a subset of samples that might contain Salmonella in order to test various culture methods to survey a larger number of samples. Fifty-five of 2,401 (2.3%) samples yielded Salmonella, representing samples obtained from 20 different locations in Monterey and San Benito Counties. Water had the highest percentage of positives (7.1%) among sample types. Wildlife yielded 20 positive samples, the highest number among sample types, with positive samples from birds (n = 105), coyotes (n = 40), deer (n = 104), elk (n = 39), wild pig (n = 41), and skunk (n = 13). Only 16 (2.6%) of the soil/sediment samples tested positive, and none of the produce samples had detectable Salmonella. Sixteen different serotypes were identified among the isolates, including S. enterica serotypes Give, Typhimurium, Montevideo, and Infantis. Fifty-four strains were sensitive to 12 tested antibiotics; one S. Montevideo strain was resistant to streptomycin and gentamicin. Pulsed-field gel electrophoresis (PFGE) analysis of the isolates revealed over 40 different pulsotypes. Several strains were isolated from water, wildlife, or soil over a period of several months, suggesting that they were persistent in this environment.
Subject(s)
Salmonella Infections, Animal/epidemiology , Salmonella enterica/genetics , Salmonella enterica/isolation & purification , Agriculture , Animals , Bacterial Typing Techniques , California , Cattle , Drug Resistance, Multiple, Bacterial/drug effects , Food Microbiology , Foodborne Diseases/microbiology , Microbial Sensitivity Tests , Oligonucleotide Array Sequence Analysis , Polymerase Chain Reaction , Prevalence , Salmonella enterica/pathogenicity , Serotyping , Soil Microbiology , Water MicrobiologyABSTRACT
The geometric complexity and stereotypy of spider webs have long generated interest in their algorithmic origin. Like other examples of animal architecture, web construction is the result of several assembly phases that are driven by distinct behavioral stages coordinated to build a successful structure. Manual observations have revealed a range of sensory cues and movement patterns used during web construction, but methods to systematically quantify the dynamics of these sensorimotor patterns are lacking. Here, we apply an analytical pipeline to quantify web-making behavior of the orb-weaver Uloborus diversus. Position tracking revealed stereotyped stages of construction that could occur in typical or atypical progressions across individuals. Using an unsupervised clustering approach, we identified general and stage-specific leg movements. A hierarchical hidden Markov model revealed that web-building stages are characterized by stereotyped sequences of actions largely shared across individuals, regardless of whether these stages progress in a typical or an atypical fashion. Web stages could be predicted based on action sequences alone, revealing that web-stage geometries are a physical manifestation of behavioral transition regimes.
Subject(s)
Spiders , Animals , Predatory BehaviorABSTRACT
Receptor tyrosine kinases (RTKs) process extracellular cues by activating a broad array of signaling proteins. Paradoxically, they often use the same proteins to elicit diverse and even opposing phenotypic responses. Binary, 'on-off' wiring diagrams are therefore inadequate to explain their differences. Here, we show that when six diverse RTKs are placed in the same cellular background, they activate many of the same proteins, but to different quantitative degrees. Additionally, we find that the relative phosphorylation levels of upstream signaling proteins can be accurately predicted using linear models that rely on combinations of receptor-docking affinities and that the docking sites for phosphoinositide 3-kinase (PI3K) and Shc1 provide much of the predictive information. In contrast, we find that the phosphorylation levels of downstream proteins cannot be predicted using linear models. Taken together, these results show that information processing by RTKs can be segmented into discrete upstream and downstream steps, suggesting that the challenging task of constructing mathematical models of RTK signaling can be parsed into separate and more manageable layers.
Subject(s)
Receptor Protein-Tyrosine Kinases/metabolism , Signal Transduction , Binding Sites , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Shc Signaling Adaptor Proteins/metabolism , Src Homology 2 Domain-Containing, Transforming Protein 1ABSTRACT
The first three members of the ErbB family of receptor tyrosine kinases activate a wide variety of signaling pathways and are frequently misregulated in cancer. Much less is known about ErbB4. Here we use tandem mass spectrometry to identify 19 sites of tyrosine phosphorylation on ErbB4, and protein microarrays to quantify biophysical interactions between these sites and virtually every SH2 and PTB domain encoded in the human genome. Our unbiased approach highlighted several previously unrecognized interactions and led to the finding that ErbB4 can recruit and activate STAT1. At a systems level, we found that ErbB4 is much more selective than the other ErbB receptors. This suggests that ErbB4 may enable ErbB2 and ErbB3 to signal independently of EGFR under normal conditions, and provides a possible explanation for the protective properties of ErbB4 in cancer.
Subject(s)
ErbB Receptors/chemistry , ErbB Receptors/metabolism , Phosphotyrosine/metabolism , Amino Acid Sequence , Cell Line , Humans , Molecular Sequence Data , Phosphorylation , Protein Array Analysis , Protein Binding , Receptor, ErbB-2/metabolism , Receptor, ErbB-3/metabolism , Receptor, ErbB-4 , STAT1 Transcription Factor/metabolism , Signal Transduction , Substrate SpecificityABSTRACT
Homologous chromosomes colocalize to regulate gene expression in processes including genomic imprinting, X-inactivation, and transvection. In Drosophila, homologous chromosomes pair throughout development, promoting transvection. The "button" model of pairing proposes that specific regions along chromosomes pair with high affinity. Here, we identify buttons interspersed across the fly genome that pair with their homologous sequences, even when relocated to multiple positions in the genome. A majority of transgenes that span a full topologically associating domain (TAD) function as buttons, but not all buttons contain TADs. Additionally, buttons are enriched for insulator protein clusters. Fragments of buttons do not pair, suggesting that combinations of elements within a button are required for pairing. Pairing is necessary but not sufficient for transvection. Additionally, pairing and transvection are stronger in some cell types than in others, suggesting that pairing strength regulates transvection efficiency between cell types. Thus, buttons pair homologous chromosomes to facilitate cell-type-specific interchromosomal gene regulation.
Subject(s)
Chromosome Pairing/genetics , Chromosomes/genetics , Drosophila melanogaster/genetics , Gene Expression Regulation , Genetic Loci , Animals , Chromatin/metabolism , Insulator Elements/genetics , TransgenesABSTRACT
Genetically encoded calcium indicators (GECIs) allow measurement of activity in large populations of neurons and in small neuronal compartments, over times of milliseconds to months. Although GFP-based GECIs are widely used for in vivo neurophysiology, GECIs with red-shifted excitation and emission spectra have advantages for in vivo imaging because of reduced scattering and absorption in tissue, and a consequent reduction in phototoxicity. However, current red GECIs are inferior to the state-of-the-art GFP-based GCaMP6 indicators for detecting and quantifying neural activity. Here we present improved red GECIs based on mRuby (jRCaMP1a, b) and mApple (jRGECO1a), with sensitivity comparable to GCaMP6. We characterized the performance of the new red GECIs in cultured neurons and in mouse, Drosophila, zebrafish and C. elegans in vivo. Red GECIs facilitate deep-tissue imaging, dual-color imaging together with GFP-based reporters, and the use of optogenetics in combination with calcium imaging.
Subject(s)
Biosensing Techniques/methods , Calcium/analysis , Intravital Microscopy/methods , Luminescent Proteins/metabolism , Neurons/chemistry , Neurons/physiology , Neurophysiology/methods , Animals , Caenorhabditis elegans , Cells, Cultured , Drosophila , Luminescent Proteins/genetics , Mice , Zebrafish , Red Fluorescent ProteinABSTRACT
Animals have a remarkable ability to track dynamic sensory information. For example, the nematode Caenorhabditis elegans can locate a diacetyl odor source across a 100,000-fold concentration range. Here, we relate neuronal properties, circuit implementation, and behavioral strategies underlying this robust navigation. Diacetyl responses in AWA olfactory neurons are concentration and history dependent; AWA integrates over time at low odor concentrations, but as concentrations rise, it desensitizes rapidly through a process requiring cilia transport. After desensitization, AWA retains sensitivity to small odor increases. The downstream AIA interneuron amplifies weak odor inputs and desensitizes further, resulting in a stereotyped response to odor increases over three orders of magnitude. The AWA-AIA circuit drives asymmetric behavioral responses to odor increases that facilitate gradient climbing. The adaptation-based circuit motif embodied by AWA and AIA shares computational properties with bacterial chemotaxis and the vertebrate retina, each providing a solution for maintaining sensitivity across a dynamic range.