scholarly journals Presynaptic MAST kinase controls opposing postsynaptic responses to convey stimulus valence in Caenorhabditis elegans

2020 ◽  
Vol 117 (3) ◽  
pp. 1638-1647 ◽  
Author(s):  
Shunji Nakano ◽  
Muneki Ikeda ◽  
Yuki Tsukada ◽  
Xianfeng Fei ◽  
Takamasa Suzuki ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Diacylglycerol Kinase ◽  
Inhibitory Response ◽  
Thermal Gradients ◽  
Postsynaptic Neuron ◽  
Presynaptic Neuron ◽  
Presynaptic Plasticity ◽  
Freely Behaving ◽  
Stimulus Valence ◽  
Thermal Stimuli

Presynaptic plasticity is known to modulate the strength of synaptic transmission. However, it remains unknown whether regulation in presynaptic neurons can evoke excitatory and inhibitory postsynaptic responses. We report here that the Caenorhabditis elegans homologs of MAST kinase, Stomatin, and Diacylglycerol kinase act in a thermosensory neuron to elicit in its postsynaptic neuron an excitatory or inhibitory response that correlates with the valence of thermal stimuli. By monitoring neural activity of the valence-coding interneuron in freely behaving animals, we show that the alteration between excitatory and inhibitory responses of the interneuron is mediated by controlling the balance of two opposing signals released from the presynaptic neuron. These alternative transmissions further generate opposing behavioral outputs necessary for the navigation on thermal gradients. Our findings suggest that valence-encoding interneuronal activity is determined by a presynaptic mechanism whereby MAST kinase, Stomatin, and Diacylglycerol kinase influence presynaptic outputs.

scholarly journals Presynaptic MAST Kinase Controls Bidirectional Post-Synaptic Responses to Convey Stimulus Valence in C. elegans

2019 ◽  
Author(s):  
Shunji Nakano ◽  
Muneki Ikeda ◽  
Yuki Tsukada ◽  
Xianfeng Fei ◽  
Takamasa Suzuki ◽  
...  
Keyword(s):  
Inhibitory Response ◽  
Thermal Gradients ◽  
Presynaptic Neuron ◽  
C Elegans ◽  
Presynaptic Plasticity ◽  
Freely Behaving ◽  
Stimulus Valence ◽  
Presynaptic Regulation ◽  
Thermal Stimuli ◽  
Synaptic Responses

AbstractPresynaptic plasticity is known to modulate the strength of synaptic transmission. However, it remains unknown whether regulation in presynaptic neurons alters the directionality –positive or negative-of postsynaptic responses. We report here that the C. elegans homologs of MAST kinase, Stomatin and Diacylglycerol kinase act in a thermosensory neuron to elicit in its postsynaptic neuron an excitatory or inhibitory response that correlates with the valence of thermal stimuli. By monitoring neural activity of the valence-coding interneuron in freely behaving animals, we show that the alteration between excitatory and inhibitory responses of the interneuron is mediated by controlling the balance of two opposing signals released from the presynaptic neuron. These alternative transmissions further generate opposing behavioral outputs necessary for the navigation on thermal gradients. Our findings reveal the previously unrecognized capability of presynaptic regulation to evoke bidirectional postsynaptic responses and suggest a molecular mechanism of determining stimulus valence.

Dopamine Activates Two Different Receptors to Produce Variability in Sign at an Identified Synapse

1999 ◽  
Vol 81 (3) ◽  
pp. 1330-1340 ◽  
Author(s):  
Neil S. Magoski ◽  
Andrew G. M. Bulloch
Keyword(s):  
Lymnaea Stagnalis ◽  
Freshwater Snail ◽  
Inhibitory Response ◽  
Postsynaptic Neuron ◽  
Presynaptic Neuron ◽  
Postsynaptic Potential ◽  
Bath Application ◽  
Continuous Bath ◽  
Two Populations ◽  
Reversal Potentials

Dopamine activates two different receptors to produce variability in sign at an identified synapse. Chemical synaptic transmission was investigated at a central synapse between identified neurons in the freshwater snail, Lymnaea stagnalis. The presynaptic neuron was the dopaminergic cell, Right Pedal Dorsal one (RPeD1). The postsynaptic neuron was Visceral Dorsal four (VD4). These neurons are components of the respiratory central pattern generator. The synapse from RPeD1 to VD4 showed variability of sign, i.e., it was either inhibitory (monophasic and hyperpolarizing), biphasic (depolarizing followed by hyperpolarizing phases), or undetectable. Both the inhibitory and biphasic synapse were eliminated by low Ca2+/high Mg2+ saline and maintained in high Ca2+/high Mg2+ saline, indicating that these two types of connections were chemical and monosynaptic. The latency of the inhibitory postsynaptic potential (IPSP) in high Ca2+/high Mg2+ saline was ∼43 ms, whereas the biphasic postsynaptic potential (BPSP) had ∼12-ms latency in either normal or high Ca2+/high Mg2+ saline. For a given preparation, when dopamine was pressured applied to the soma of VD4, it always elicited the same response as the synaptic input from RPeD1. Thus, for a VD4 neuron receiving an IPSP from RPeD1, pressure application of dopamine to the soma of VD4 produced an inhibitory response similar to the IPSP. The reversal potentials of the IPSP and the inhibitory dopamine response were both approximately −90 mV. For a VD4 neuron with a biphasic input from RPeD1, pressure-applied dopamine produced a biphasic response similar to the BPSP. The reversal potentials of the depolarizing phase of the BPSP and the biphasic dopamine response were both approximately −44 mV, whereas the reversal potentials for the hyperpolarizing phases were both approximately −90 mV. The hyperpolarizing but not the depolarizing phase of the BPSP and the biphasic dopamine response was blocked by the d-2 dopaminergic antagonist (±) sulpiride. Previously, our laboratory demonstrated that both IPSP and the inhibitory dopamine response are blocked by (±) sulpiride. Conversely, the depolarizing phase of both the BPSP and the biphasic dopamine response was blocked by the Cl− channel antagonist picrotoxin. Finally, both phases of the BPSP and the biphasic dopamine response were desensitized by continuous bath application of dopamine. These results indicate that the biphasic RPeD1 → VD4 synapse is dopaminergic. Collectively, these data suggest that the variability in sign (inhibitory vs. biphasic) at the RPeD1 → VD4 synapse is due to activation of two different dopamine receptors on the postsynaptic neuron VD4. This demonstrates that two populations of receptors can produce two different forms of transmission, i.e., the inhibitory and biphasic forms of the single RPeD1 → VD4 synapse.

scholarly journals The effect of opioids and their antagonists on the nocifensive response of Caenorhabditis elegans to noxious thermal stimuli

2009 ◽  
Vol 9 (3-4) ◽  
pp. 195-200 ◽  
Author(s):  
F. Nieto-Fernandez ◽  
S. Andrieux ◽  
S. Idrees ◽  
C. Bagnall ◽  
S. C. Pryor ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Thermal Stimuli

Automated imaging of neuronal activity in freely behaving Caenorhabditis elegans

2010 ◽  
Vol 187 (2) ◽  
pp. 229-234 ◽  
Author(s):  
Juliette Ben Arous ◽  
Yoshinori Tanizawa ◽  
Ithai Rabinowitch ◽  
Didier Chatenay ◽  
William R. Schafer
Keyword(s):  
Caenorhabditis Elegans ◽  
Neuronal Activity ◽  
Automated Imaging ◽  
Freely Behaving

scholarly journals Real-time multimodal optical control of neurons and muscles in freely behaving Caenorhabditis elegans

2011 ◽  
Vol 8 (2) ◽  
pp. 153-158 ◽  
Author(s):  
Jeffrey N Stirman ◽  
Matthew M Crane ◽  
Steven J Husson ◽  
Sebastian Wabnig ◽  
Christian Schultheis ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Real Time ◽  
Optical Control ◽  
Freely Behaving

scholarly journals Modeling noise mechanisms in neuronal synaptic transmission

2017 ◽  
Author(s):  
Abhyudai Singh
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
Action Potentials ◽  
Spike Timing ◽  
Critical Threshold ◽  
Model Parameters ◽  
Postsynaptic Neuron ◽  
Presynaptic Neuron ◽  
Vesicle Release ◽  
First Time

In the nervous system, communication occurs via synaptic transmission where signaling molecules (neurotransmitters) are released by the presynaptic neuron, and they influence electrical activity of another neuron (postsynaptic neuron). The inherent probabilistic release of neurotransmitters is a significant source of noise that critically impacts the timing of spikes (action potential) in the postsynaptic neuron. We develop a stochastic model that incorporates noise mechanisms in synaptic transmission, such as, random docking of neurotransmitter-filled vesicle to a finite number of docking sites, with each site having a probability of vesicle release upon arrival of an action potential. This random, burst-like release of neurotransmitters serves as an input to an integrate-and-fire model, where spikes in the postsynaptic neuron are triggered when its membrane potential reaches a critical threshold for the first time. We derive novel analytical results for the probability distribution function of spike timing, and systematically investigate how underlying model parameters and noise processes regulate variability in the inter-spike times. Interestingly, in some parameter regimes, independent arrivals of action potentials in the presynaptic neuron generate strong dependencies in the spike timing of the postsynaptic neuron. Finally, we argue that probabilistic release of neurotransmitters is not only a source of disturbance, but plays a beneficial role in synaptic information processing.

General Psychopharmacology

2018 ◽  
Author(s):  
Shadi Doroudgar ◽  
Paul Perry
Keyword(s):  
Butyric Acid ◽  
Synaptic Cleft ◽  
Terminal Segment ◽  
Clinical Effects ◽  
Postsynaptic Neuron ◽  
Presynaptic Neuron ◽  
Initial Development ◽  
Amino Butyric Acid ◽  
Enzyme Degradation ◽  
Selection Of

Initial development of neuropsychiatric medications relied heavily on serendipitous discovery rather than targeted drug designs. Nowadays, drug discovery targets include receptors, enzymes, and transporters. The human brain comprises many neurons, each being connected to other neurons via synapses. Neurotransmission occurs when a presynaptic neuron projects its terminal segment to form a connection or synapse with an adjacent postsynaptic neuron. When stimulated, neurotransmitters that are stored in small vesicles in the presynaptic neuron are released into an interneuronal gap called the synaptic cleft. Serotonin, dopamine, norepinephrine, γ-amino butyric acid, glutamate, and acetylcholine are among the primary neurotransmitters and chemicals that play important roles in neuropsychiatric functions. As such, they are often common targets of drug development. Grasping the basics of neurotransmission, enzyme degradation, and receptor and transporter pharmacology is essential in understanding today’s FDA-approved pharmaceuticals. This neuropharmacology primer will allow the rational and appropriate clinical selection of pharmacotherapy and accurate anticipation of clinical effects following use.   This review contains 1 figure and 45 references Key Words: acetylcholine, dopamine, γ-amino butyric acid, glutamate, neurotransmission, norepinephrine, pharmacology, psychiatric medications, psychopharmacology, receptor, serotonin

scholarly journals Whole-brain calcium imaging with cellular resolution in freely behaving Caenorhabditis elegans

2015 ◽  
Vol 113 (8) ◽  
pp. E1074-E1081 ◽  
Author(s):  
Jeffrey P. Nguyen ◽  
Frederick B. Shipley ◽  
Ashley N. Linder ◽  
George S. Plummer ◽  
Mochi Liu ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Animal Behavior ◽  
Calcium Imaging ◽  
Large Scale ◽  
Calcium Transients ◽  
Whole Brain ◽  
Cellular Resolution ◽  
Calcium Indicator ◽  
Custom Software ◽  
Freely Behaving

The ability to acquire large-scale recordings of neuronal activity in awake and unrestrained animals is needed to provide new insights into how populations of neurons generate animal behavior. We present an instrument capable of recording intracellular calcium transients from the majority of neurons in the head of a freely behaving Caenorhabditis elegans with cellular resolution while simultaneously recording the animal’s position, posture, and locomotion. This instrument provides whole-brain imaging with cellular resolution in an unrestrained and behaving animal. We use spinning-disk confocal microscopy to capture 3D volumetric fluorescent images of neurons expressing the calcium indicator GCaMP6s at 6 head-volumes/s. A suite of three cameras monitor neuronal fluorescence and the animal’s position and orientation. Custom software tracks the 3D position of the animal’s head in real time and two feedback loops adjust a motorized stage and objective to keep the animal’s head within the field of view as the animal roams freely. We observe calcium transients from up to 77 neurons for over 4 min and correlate this activity with the animal’s behavior. We characterize noise in the system due to animal motion and show that, across worms, multiple neurons show significant correlations with modes of behavior corresponding to forward, backward, and turning locomotion.

Paired individual and mean postsynaptic currents recorded in four-cell networks of Aplysia

1990 ◽  
Vol 63 (5) ◽  
pp. 1226-1240 ◽  
Author(s):  
D. Gardner
Keyword(s):  
Decay Time ◽  
Time Course ◽  
Current Amplitude ◽  
Postsynaptic Neuron ◽  
Synaptic Current ◽  
Presynaptic Neuron ◽  
Mean Values ◽  
Postsynaptic Currents ◽  
Cell Networks ◽  
Presynaptic Neurons

1. Presynaptic neurons B4 and B5 of Aplysia buccal ganglia produce similar inhibitory postsynaptic currents (PSCs) in several postsynaptic follower cells. Two previous papers have characterized the variability of synaptic current amplitude and decay time both for individual PSCs and also for mean values characterizing synapses and have compared PSC amplitude and time course at different synapses sharing a common presynaptic or postsynaptic neuron. 2. To distinguish similarity in synaptic current amplitude or decay introduced by a common pre- or postsynaptic neuron from similarity because of factors common to the particular ganglion or animal, paired synapses were analyzed in four-cell networks in which each of two identified presynaptic neurons produces similar PSCs in each of two postsynaptic cells. Pairing the same synaptic data by common presynaptic or postsynaptic neuron tests if the presynaptic or postsynaptic element partially specifies a parameter; cross-pairing controls for more global factors. Paired values of peak conductance gpeak and decay time constant tau were compared for both individual sequential PSCs and for averages characterizing synapses. Analyses of individual PSCs examine processes affecting synaptic plasticity on a time scale of seconds to minutes, while average values compare more slowly varying factors. 3. Peak amplitudes were compared between individual PSCs in each of 24 paired sets. Correlations of gpeak fluctuations were significantly larger for PSCs produced by the same presynaptic neuron than for postsynaptic or cross pairings (P less than 0.05), consistent with partially correlated fluctuations in transmitter release at different presynaptic terminals. 4. Firing rates of individual presynaptic neurons were modulated to induce variability of test PSCs. These manipulations altered synaptic peak amplitudes in paired postsynaptic neurons, although not to the same degree. Manipulation of a single presynaptic neuron modulated input from that neuron alone to common postsynaptic cells without any effect on input from the paired presynaptic neuron. When fluctuations in the amplitude of gpeak were examined in runs incorporating presynaptic modulation, correlations were strong for sets of PSCs sharing a common presynaptic neuron (R = 0.87), significantly greater (P less than 0.001) than for other pairings. 5. In contrast to the partial presynaptic specification of fluctuations of individual PSCs, values of synaptic amplitude and time course averaged over 21-132 PSCs at a given synapse reflect postsynaptic determinants. Mean values of gpeak characterizing synapses paired by common postsynaptic cell are highly similar (P = 0.0001), in contrast to the lack of similarity seen when the same data are presynaptically (P = 0.11) or cross (P = 0.36) paired.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Behavioral response of Caenorhabditis elegans to localized thermal stimuli

2013 ◽  
Vol 14 (1) ◽  
pp. 66 ◽  
Author(s):  
Aylia Mohammadi ◽  
Jarlath Byrne Rodgers ◽  
Ippei Kotera ◽  
William S Ryu
Keyword(s):  
Caenorhabditis Elegans ◽  
Behavioral Response ◽  
Thermal Stimuli
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