scholarly journals INX-18 and INX-19 play distinct roles in electrical synapses that modulate aversive behavior in Caenorhabditis elegans

2019 ◽  
Author(s):  
Lisa Voelker ◽  
Bishal Upadhyaya ◽  
Denise M. Ferkey ◽  
Sarah Woldemariam ◽  
Noelle D. L’Etoile ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Internal State ◽  
Nerve Ring ◽  
Electrical Synapse ◽  
Electrical Synapses ◽  
C Elegans ◽  
Internal States ◽  
Sensory Responses ◽  
Aversive Behavior ◽  
Sites Of Action

AbstractIn order to respond to changing environments and fluctuations in internal states, animals adjust their behavior through diverse neuromodulatory mechanisms. In this study we show that electrical synapses between the ASH primary quinine-detecting sensory neurons and the neighboring ASK neurons are required for modulating the aversive response to the bitter tastant quinine in C. elegans. Mutant worms that lack the electrical synapse proteins INX-18 and INX-19 become hypersensitive to dilute quinine. Cell-specific rescue experiments indicate that inx-18 operates in ASK while inx-19 is required in both ASK and ASH for proper quinine sensitivity. Imaging analyses find that INX-19 in ASK and ASH localizes to the same regions in the nerve ring, suggesting that both sides of ASK-ASH electrical synapses contain INX-19. While inx-18 and inx-19 mutant animals have a similar behavioral phenotype, several lines of evidence suggest the proteins encoded by these genes play different roles in modulating the aversive quinine response. First, INX-18 and INX-19 localize to different regions of the nerve ring, indicating that they are not present in the same synapses. Second, removing inx-18 disrupts the distribution of INX-19, while removing inx-19 does not alter INX-18 localization. Finally, by using a fluorescent cGMP reporter, we find that INX-18 and INX-19 have distinct roles in establishing cGMP levels in ASK and ASH. Together, these results demonstrate that electrical synapses containing INX-18 and INX-19 facilitate modulation of ASH nociceptive signaling. Our findings support the idea that a network of electrical synapses mediates cGMP exchange between neurons, enabling modulation of sensory responses and behavior.Author SummaryAnimals are constantly adjusting their behavior to respond to changes in the environment or to their internal state. This behavior modulation is achieved by altering the activity of neurons and circuits through a variety of neuroplasticity mechanisms. Chemical synapses are known to impact neuroplasticity in several different ways, but the diversity of mechanisms by which electrical synapses contribute is still being investigated. Electrical synapses are specialized sites of connection between neurons where ions and small signaling molecules can pass directly from one cell to the next. By passing small molecules through electrical synapses, neurons may be able to modify the activity of their neighbors. In this study we identify two genes that contribute to electrical synapses between two sensory neurons in C. elegans. We show that these electrical synapses are crucial for proper modulation of sensory responses, as without them animals are overly responsive to an aversive stimulus. In addition to pinpointing their sites of action, we present evidence that they may be contributing to neuromodulation by facilitating passage of the small molecule cGMP between neurons. Our work provides evidence for a role of electrical synapses in regulating animal behavior.

scholarly journals cAMP controls a trafficking mechanism that directs the neuron specificity and subcellular placement of electrical synapses

2021 ◽  
Author(s):  
Sierra Palumbos ◽  
Rachel Skelton ◽  
Rebecca McWhirter ◽  
Amanda Mitchell ◽  
Isaiah Swann ◽  
...  
Keyword(s):  
Nervous System ◽  
Gap Junction ◽  
Motor Neurons ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Electrical Synapse ◽  
Transcriptional Program ◽  
Electrical Synapses ◽  
C Elegans

Electrical synapses are established between specific neurons and within distinct subcellular compartments, but the mechanisms that direct gap junction assembly in the nervous system are largely unknown. Here we show that a transcriptional program tunes cAMP signaling to direct the neuron-specific assembly and placement of electrical synapses in the C. elegans motor circuit. For these studies, we use live cell imaging to visualize electrical synapses in vivo and a novel optogenetic assay to confirm that they are functional. In VA motor neurons, the UNC-4 transcription factor blocks expression of cAMP antagonists that promote gap junction miswiring. In unc-4 mutants, VA electrical synapses are established with an alternative synaptic partner and are repositioned from the VA axon to soma. We show that cAMP counters these effects by driving gap junction trafficking into the VA axon for electrical synapse assembly. Thus, our experiments in an intact nervous system establish that cAMP regulates gap junction trafficking for the biogenesis of electrical synapses.

Amygdala neuronal ensembles dynamically encode behavioral states

2018 ◽  
Author(s):  
Jan Gründemann ◽  
Yael Bitterman ◽  
Tingjia Lu ◽  
Sabine Krabbe ◽  
Benjamin F. Grewe ◽  
...  
Keyword(s):  
Internal State ◽  
Relative Activity ◽  
Activity Levels ◽  
Basal Nucleus ◽  
State Dependent ◽  
Internal States ◽  
Behavioral States ◽  
Sensory Responses ◽  
Motivated Behaviors ◽  
External Stimuli

AbstractInternal states, including affective or homeostatic states, are important behavioral motivators. The amygdala is a key brain region involved in the regulation of motivated behaviors, yet how distinct internal states are represented in amygdala circuits is unknown. Here, by imaging somatic neural calcium dynamics in freely moving mice, we identify changes in the relative activity levels of two major, non-overlapping populations of principal neurons in the basal nucleus of the amygdala (BA) that predict switches between exploratory and non-exploratory (defensive, anxiety-like) behavioral states across different environments. Moreover, the amygdala widely broadcasts internal state information via several output pathways to larger brain networks, and sensory responses in BA occur independently of behavioral state encoding. Thus, the brain processes external stimuli and internal states in an orthogonal manner, which may facilitate rapid and flexible selection of appropriate, state-dependent behavioral responses.

scholarly journals Feeding state functionally reconfigures a sensory circuit to drive thermosensory behavioral plasticity

2020 ◽  
Author(s):  
Asuka Takeishi ◽  
Jihye Yeon ◽  
Nathan Harris ◽  
Wenxing Yang ◽  
Piali Sengupta
Keyword(s):  
Sensory Neurons ◽  
Behavioral Plasticity ◽  
Internal State ◽  
Behavioral Flexibility ◽  
Survival Strategies ◽  
C Elegans ◽  
The Core ◽  
State Dependent ◽  
Neuronal Mechanisms ◽  
Temperature Responses

AbstractInternal state alters sensory behaviors to optimize survival strategies. The neuronal mechanisms underlying hunger-dependent behavioral plasticity are not fully characterized. Here we show that feeding state regulates C. elegans negative thermotaxis behavior by engaging a modulatory circuit whose activity gates the output of the core thermotaxis network. Feeding state does not alter the activity of the core thermotaxis circuit comprised of AFD thermosensory and AIY interneurons. Instead, prolonged food deprivation potentiates temperature responses in the AWC sensory neurons, which inhibit the postsynaptic AIA interneurons to override and disrupt AFD-driven thermotaxis behavior. Acute inhibition and activation of AWC and AIA, respectively, restores negative thermotaxis in starved animals. We find that state-dependent modulation of AWC-AIA temperature responses requires INS-1 insulin-like peptide signaling from the gut and DAF-16 FOXO function in AWC. Our results describe a mechanism by which functional reconfiguration of a sensory network via gut-brain signaling drives state-dependent behavioral flexibility.

scholarly journals Neural mechanisms driving hunger-induced changes in sensory perception and behavior in Caenorhabditis elegans

2017 ◽  
Author(s):  
Hiu E. Lau ◽  
Zachary T. Cecere ◽  
Zheng Liu ◽  
Claire J. Yang ◽  
Tatyana O. Sharpee ◽  
...  
Keyword(s):  
Internal State ◽  
Sensory Perception ◽  
Neuronal Dynamics ◽  
C Elegans ◽  
Appetitive Behavior ◽  
Internal States ◽  
Body Wall Muscles ◽  
Peptide Signals ◽  
Induced Changes ◽  
And Behavior

SummaryWhile much is known about how external cues affect neural circuits, less is known about how internal states modify their function. We acutely food-deprived C. elegans and analyzed its responses in integrating attractant and repellent signals. We show that food deprivation leads to a reversible decline in repellent sensitivity; with no effect on appetitive behavior allowing animals to engage in higher risk behavior. Multiple tissues including the intestine and body wall muscles use a conserved transcription factor, MondoA, to detect the lack of food and release AEX-5 convertase processed peptides from dense core vesicles. Subsequently, ASI chemosensory neurons use the DAF-2 insulin receptor and non-canonical signaling to integrate the tissue-released peptide signals modifying their stimulus-evoked adaptation rate. We suggest that altering ASI neuronal dynamics affects its function and modifies behavior. Together, these studies show how internal state signals modify sensory perception and risk assessment to generate flexible behaviors.

scholarly journals Feeding state functionally reconfigures a sensory circuit to drive thermosensory behavioral plasticity

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Asuka Takeishi ◽  
Jihye Yeon ◽  
Nathan Harris ◽  
Wenxing Yang ◽  
Piali Sengupta
Keyword(s):  
Sensory Neurons ◽  
Behavioral Plasticity ◽  
Internal State ◽  
Behavioral Flexibility ◽  
Survival Strategies ◽  
C Elegans ◽  
The Core ◽  
State Dependent ◽  
Neuronal Mechanisms ◽  
Temperature Responses

Internal state alters sensory behaviors to optimize survival strategies. The neuronal mechanisms underlying hunger-dependent behavioral plasticity are not fully characterized. Here we show that feeding state alters C. elegans thermotaxis behavior by engaging a modulatory circuit whose activity gates the output of the core thermotaxis network. Feeding state does not alter the activity of the core thermotaxis circuit comprised of AFD thermosensory and AIY interneurons. Instead, prolonged food deprivation potentiates temperature responses in the AWC sensory neurons, which inhibit the postsynaptic AIA interneurons to override and disrupt AFD-driven thermotaxis behavior. Acute inhibition and activation of AWC and AIA, respectively, restores negative thermotaxis in starved animals. We find that state-dependent modulation of AWC-AIA temperature responses requires INS-1 insulin-like peptide signaling from the gut and DAF-16/FOXO function in AWC. Our results describe a mechanism by which functional reconfiguration of a sensory network via gut-brain signaling drives state-dependent behavioral flexibility.

scholarly journals Plasticity of the electrical connectome of C. elegans

2018 ◽  
Author(s):  
Abhishek Bhattacharya ◽  
Ulkar Aghayeva ◽  
Emily Berghoff ◽  
Oliver Hobert
Keyword(s):  
Nervous System ◽  
Expression Patterns ◽  
Electrical Synapse ◽  
Neuron Type ◽  
Electrical Synapses ◽  
C Elegans ◽  
Regulatory Strategies ◽  
A Genome ◽  
Specific Manner ◽  
Foxo Transcription Factors

AbstractThe patterns of electrical synapses of an animal nervous system (“electrical connectome”), as well as the functional properties and plasticity of electrical synapses, are defined by the neuron type-specific complement of electrical synapse constituents. We systematically examine here properties of the electrical connectome of the nematode C. elegans through a genome- and nervous system-wide analysis of the expression pattern of the central components of invertebrate electrical synapses, the innexins, revealing highly complex combinatorial patterns of innexin expression throughout the nervous system. We find that the complex expression patterns of 12 out of 14 neuronally expressed innexins change in a strikingly neuron type-specific manner throughout most of the nervous system, if animals encounter harsh environmental conditions and enter the dauer arrest stage. We systematically describe the plasticity of locomotory patterns of dauer stage animals and, by analyzing several individual electrical synapses, we demonstrate that dauer stage-specific electrical synapse remodeling is responsible for specific aspects of the altered locomotory patterns as well as altered chemosensory behavior of dauer stage animals. We describe an intersectional gene regulatory mechanism, involving terminal selector and FoxO transcription factors that are responsible for inducing innexin expression changes in a neuron type- and environment-specific manner. Taken together, our studies illustrate the remarkably dynamic nature of electrical synapses on a nervous system-wide level and describe regulatory strategies for how these alterations are achieved.

scholarly journals The G Protein regulators EGL-10 and EAT-16, the Giα GOA-1 and the Gqα EGL-30 modulate the response of the C. elegans ASH polymodal nociceptive sensory neurons to repellents

BMC Biology ◽  
2010 ◽  
Vol 8 (1) ◽  
pp. 138 ◽  
Author(s):  
Giovanni Esposito ◽  
Maria R Amoroso ◽  
Carmela Bergamasco ◽  
Elia Di Schiavi ◽  
Paolo Bazzicalupo
Keyword(s):  
G Protein ◽  
Sensory Neurons ◽  
C Elegans

scholarly journals Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mercedes M. Pérez-Jiménez ◽  
José M. Monje-Moreno ◽  
Ana María Brokate-Llanos ◽  
Mónica Venegas-Calerón ◽  
Alicia Sánchez-García ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Caenorhabditis Elegans ◽  
Protein Aggregation ◽  
Steroid Hormones ◽  
Sensory Neurons ◽  
Environmental Cues ◽  
Steroid Sulfatase ◽  
Loss Of Function ◽  
C Elegans ◽  
Age Related

AbstractAging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity. Here we show that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones, increases longevity and ameliorates protein aggregation diseases. This increased longevity requires factors involved in germline-mediated longevity (daf-16, daf-12, kri-1, tcer-1 and daf-36 genes) although sul-2 mutations do not affect fertility. Interestingly, sul-2 is only expressed in sensory neurons, suggesting a regulation of sulfated hormones state by environmental cues. Treatment with the specific STS inhibitor STX64, as well as with testosterone-derived sulfated hormones reproduces the longevity phenotype of sul-2 mutants. Remarkably, those treatments ameliorate protein aggregation diseases in C. elegans, and STX64 also Alzheimer’s disease in a mammalian model. These results open the possibility of reallocating steroid sulfatase inhibitors or derivates for the treatment of aging and aging related diseases.

scholarly journals Polymodal Functionality of C. elegans OLL Neurons in Mechanosensation and Thermosensation

2021 ◽  
Author(s):  
Yuedan Fan ◽  
Wenjuan Zou ◽  
Jia Liu ◽  
Umar Al-Sheikh ◽  
Hankui Cheng ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Sensory Neurons ◽  
Molecular Mechanisms ◽  
Temperature Sensitive ◽  
Cold Sensation ◽  
Cold Response ◽  
C Elegans ◽  
Sensory Modalities ◽  
A Cell ◽  
Bona Fide

AbstractSensory modalities are important for survival but the molecular mechanisms remain challenging due to the polymodal functionality of sensory neurons. Here, we report the C. elegans outer labial lateral (OLL) sensilla sensory neurons respond to touch and cold. Mechanosensation of OLL neurons resulted in cell-autonomous mechanically-evoked Ca2+ transients and rapidly-adapting mechanoreceptor currents with a very short latency. Mechanotransduction of OLL neurons might be carried by a novel Na+ conductance channel, which is insensitive to amiloride. The bona fide mechano-gated Na+-selective degenerin/epithelial Na+ channels, TRP-4, TMC, and Piezo proteins are not involved in this mechanosensation. Interestingly, OLL neurons also mediated cold but not warm responses in a cell-autonomous manner. We further showed that the cold response of OLL neurons is not mediated by the cold receptor TRPA-1 or the temperature-sensitive glutamate receptor GLR-3. Thus, we propose the polymodal functionality of OLL neurons in mechanosensation and cold sensation.

Impaired discrimination of a subanesthetic dose of ketamine in a maternal immune activation model of schizophrenia risk

2021 ◽  
pp. 026988112110297
Author(s):  
Wayne Meighan ◽  
Thomas W Elston ◽  
David Bilkey ◽  
Ryan D Ward
Keyword(s):  
Animal Models ◽  
Drug Discrimination ◽  
Immune Activation ◽  
Internal State ◽  
Nmda Receptor Antagonist ◽  
Activation Model ◽  
Data Link ◽  
Maternal Immune Activation ◽  
Internal States ◽  
Reliable Methods

Background: Animal models of psychiatric diseases suffer from a lack of reliable methods for accurate assessment of subjective internal states in nonhumans. This gap makes translation of results from animal models to patients particularly challenging. Aims/methods: Here, we used the drug-discrimination paradigm to allow rats that model a risk factor for schizophrenia (maternal immune activation, MIA) to report on the subjective internal state produced by a subanesthetic dose of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. Results/outcomes: The MIA rats’ discrimination of ketamine was impaired relative to controls, both in the total number of rats that acquired and the asymptotic level of discrimination accuracy. This deficit was not due to a general inability to learn to discriminate an internal drug cue or internal state generally, as MIA rats were unimpaired in the learning and acquisition of a morphine drug discrimination and were as sensitive to the internal state of satiety as controls. Furthermore, the deficit was not due to a decreased sensitivity to the physiological effects of ketamine, as MIA rats showed increased ketamine-induced locomotor activity. Finally, impaired discrimination of ketamine was only seen at subanesthetic doses which functionally correspond to psychotomimetic doses in humans. Conclusion: These data link changes in NMDA responses to the MIA model. Furthermore, they confirm the utility of the drug-discrimination paradigm for future inquiries into the subjective internal state produced in models of schizophrenia and other developmental diseases.

Sign in / Sign up

Export Citation Format

Share Document