17 research outputs found
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Cell-intrinsic Mechanisms of Odor Preference and Discrimination in C. elegans Olfactory Neurons
Two fundamental questions regarding the neural basis of sensation are how stimuli are encoded in the nervous system and how animals discriminate between stimuli. In chemosensory systems there is a diversity of chemoreceptors that matches the diversity in chemical space. Volatile chemicals, or odors, are often represented in the periphery by a combinatorial code of neuronal activity. By contrast, the more simple qualities of soluble tasted chemicals, such as bitter and sweet, are sensed by anatomically distinct populations of cells that drive stereotyped behaviors. The nematode Caenorhabditis elegans senses and discriminates between many soluble and volatile chemicals, and exhibits plasticity in chemosensory behavior. This thesis addresses the cellular and molecular mechanisms underlying C. elegans chemosensory behaviors through genetic analysis, quantitative analysis of behavior and measurement of neuronal activity.C. elegans discriminates among certain food-related odors by mechanisms that require multiple olfactory cell types. In this study, animals with only one type of functional neuron are shown to discriminate between some odors. Therefore, cell-intrinsic mechanisms may participate in certain kinds of odor discrimination, in addition to combinatorial mechanisms.Some chemosensory cues drive innate behaviors by activating a hardwired, "labeled-line" circuit connecting sensory input to motor output. However, this thesis shows that C. elegans AWC olfactory neurons that drive attraction can also drive avoidance in some contexts. cGMP and PKC signaling in olfactory neurons reverses odor preference by altering neurotransmission at the first sensory synapse. Therefore, a hardwired circuit can generate opposite behavioral outcomes through alternative modes of synaptic transmission.Further analysis of cGMP signaling mutants revealed that neuronal cGMP signaling is involved not only in chemosensory behaviors in C. elegans but also in regulating adaptive behavioral responses to osmotic stress. These results provide a striking parallel to the role of cGMP signaling in vertebrate water homeostasis. The adaptive response to osmotic stress has been mapped to a set of candidate mechanosensitive neurons. These neurons are distinct from those that sense mechanical touch stimuli along the body or the nose. Thus mechanosensation and osmosensation may arise from segregated neuronal pathways, which could facilitate discrimination between the different types of mechanical stimuli
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Catecholamine receptor polymorphisms affect decision-making in C. elegans.
Innate behaviours are flexible: they change rapidly in response to transient environmental conditions, and are modified slowly by changes in the genome. A classical flexible behaviour is the exploration-exploitation decision, which describes the time at which foraging animals choose to abandon a depleting food supply. We have used quantitative genetic analysis to examine the decision to leave a food patch in Caenorhabditis elegans. Here we show that patch-leaving is a multigenic trait regulated in part by naturally occurring non-coding polymorphisms in tyra-3 (tyramine receptor 3), which encodes a G-protein-coupled catecholamine receptor related to vertebrate adrenergic receptors. tyra-3 acts in sensory neurons that detect environmental cues, suggesting that the internal catecholamines detected by tyra-3 regulate responses to external conditions. These results indicate that genetic variation and environmental cues converge on common circuits to regulate behaviour, and suggest that catecholamines have an ancient role in regulating behavioural decisions
The Star-Nosed Mole Reveals Clues to the Molecular Basis of Mammalian Touch
<div><p>Little is known about the molecular mechanisms underlying mammalian touch transduction. To identify novel candidate transducers, we examined the molecular and cellular basis of touch in one of the most sensitive tactile organs in the animal kingdom, the star of the star-nosed mole. Our findings demonstrate that the trigeminal ganglia innervating the star are enriched in tactile-sensitive neurons, resulting in a higher proportion of light touch fibers and lower proportion of nociceptors compared to the dorsal root ganglia innervating the rest of the body. We exploit this difference using transcriptome analysis of the star-nosed mole sensory ganglia to identify novel candidate mammalian touch and pain transducers. The most enriched candidates are also expressed in mouse somatosesensory ganglia, suggesting they may mediate transduction in diverse species and are not unique to moles. These findings highlight the utility of examining diverse and specialized species to address fundamental questions in mammalian biology.</p> </div
Expression of candidate transducers in mouse ganglia.
<p><i>(A)</i> Ion channels enriched in mole TG and DRG that were amplified by RT-PCR from mouse TG and DRG. All genes were amplified independently from TG and DRG samples isolated from two mice. Channels shown in bold are candidates that have not been previously reported as expressed in somatosensory neurons. (B) qPCR analysis of selected genes in mouse TG and kidney. Results show average expression normalized to Gapdh (n = 3). Error bars represent s.e.m.</p
Functional enrichment of light touch-sensitive neurons in the star-nosed mole trigeminal ganglia.
<p>(<i>A</i>) Representative images of Fura-2 loaded star-nosed mole TG and DRG neurons before and after exposure to 10% radial stretch and capsaicin (1 µM). (<i>B</i>) Average percentage of TG (green) and DRG (grey) neurons activated by capsaicin (Cap), mustard oil (MO), menthol (Me), hydroxy-α-sanshool (San), hypotonic solution (Hypo) and 10% radial stretch (Str) (error bars represent s.e.m. n = 4 samples, **p< 0.01, *p< 0.05 by one way ANOVA).</p