scholarly journals A computational analysis of signal fidelity in the rostral nucleus of the solitary tract

2018 ◽  
Vol 119 (3) ◽  
pp. 771-785
Author(s):  
Alison Boxwell ◽  
David Terman ◽  
Marion Frank ◽  
Yuchio Yanagawa ◽  
Joseph B. Travers
Keyword(s):  
Frequency Tuning ◽  
Afferent Input ◽  
Firing Frequency ◽  
Projection Neurons ◽  
Solitary Tract ◽  
Model Cell ◽  
Rostral Nucleus ◽  
Local Circuits ◽  
The Impact

Neurons in the rostral nucleus of the solitary tract (rNST) convey taste information to both local circuits and pathways destined for forebrain structures. This nucleus is more than a simple relay, however, because rNST neurons differ in response rates and tuning curves relative to primary afferent fibers. To systematically study the impact of convergence and inhibition on firing frequency and breadth of tuning (BOT) in rNST, we constructed a mathematical model of its two major cell types: projection neurons and inhibitory neurons. First, we fit a conductance-based neuronal model to data derived from whole cell patch-clamp recordings of inhibitory and noninhibitory neurons in a mouse expressing Venus under the control of the VGAT promoter. We then used in vivo chorda tympani (CT) taste responses as afferent input to modeled neurons and assessed how the degree and type of convergence influenced model cell output frequency and BOT for comparison with in vivo gustatory responses from the rNST. Finally, we assessed how presynaptic and postsynaptic inhibition impacted model cell output. The results of our simulations demonstrated 1) increasing numbers of convergent afferents (2–10) result in a proportional increase in best-stimulus firing frequency but only a modest increase in BOT, 2) convergence of afferent input selected from the same best-stimulus class of CT afferents produced a better fit to real data from the rNST compared with convergence of randomly selected afferent input, and 3) inhibition narrowed the BOT to more realistically model the in vivo rNST data. NEW & NOTEWORTHY Using a combination of in vivo and in vitro neurophysiology together with conductance-based modeling, we show how patterns of convergence and inhibition interact in the rostral (gustatory) solitary nucleus to maintain signal fidelity. Although increasing convergence led to a systematic increase in firing frequency, tuning specificity was maintained with a pattern of afferent inputs sharing the best-stimulus compared with random inputs. Tonic inhibition further enhanced response fidelity.

scholarly journals Physiological and anatomical properties of intramedullary projection neurons in rat rostral nucleus of the solitary tract

2013 ◽  
Vol 110 (5) ◽  
pp. 1130-1143 ◽  
Author(s):  
James A. Corson ◽  
Robert M. Bradley
Keyword(s):  
Sensory Information ◽  
Afferent Input ◽  
Morphological Properties ◽  
Projection Neurons ◽  
Spine Density ◽  
Solitary Tract ◽  
Patch Clamp Recording ◽  
Primary Afferent ◽  
Rostral Nucleus ◽  
Gustatory Information

The rostral nucleus of the solitary tract (rNTS), the first-order relay of gustatory information, not only transmits sensory information to more rostral brain areas but also connects to various brain stem sites responsible for orofacial reflex activities. While much is known regarding ascending projections to the parabrachial nucleus, intramedullary projections to the reticular formation (which regulate oromotor reflexive behaviors) remain relatively unstudied. The present study examined the intrinsic firing properties of these neurons as well as their morphological properties and synaptic connectivity with primary sensory afferents. Using in vitro whole cell patch-clamp recording, we found that intramedullary projection neurons respond to depolarizing current injection with either tonic or bursting action potential trains and subsets of these groups of neurons express A-type potassium, H-like, and postinhibitory rebound currents. Approximately half of the intramedullary projection neurons tested received monosynaptic innervation from primary afferents, while the rest received polysynaptic innervation, indicating that at least a subpopulation of these neurons can be directly activated by incoming sensory information. Neuron morphological reconstructions revealed that many of these neurons possessed numerous dendritic spines and that neurons receiving monosynaptic primary afferent input have a greater spine density than those receiving polysynaptic primary afferent input. These results reveal that intramedullary projection neurons represent a heterogeneous class of rNTS neurons and, through both intrinsic voltage-gated ion channels and local circuit interactions, transform incoming gustatory information into signals governing oromotor reflexive behaviors.

scholarly journals Mammalian octopus cells are direction selective to frequency sweeps by synaptic sequence detection

2021 ◽  
Author(s):  
Hsin-Wei Lu ◽  
Philip H Smith ◽  
Philip Joris
Keyword(s):  
Auditory Nerve ◽  
Frequency Tuning ◽  
Direction Selectivity ◽  
Coincidence Detection ◽  
Biophysical Model ◽  
Projection Neurons ◽  
Sequence Detection ◽  
Frequency Sweeps ◽  
Activation Sequence

Octopus cells are remarkable projection neurons of the mammalian cochlear nucleus, with extremely fast membranes and wide frequency tuning. They are considered prime examples of coincidence detectors but are poorly characterized in vivo. We discover that octopus cells are selective to frequency sweep direction, a feature that is absent in their auditory nerve inputs. In vivo intracellular recordings reveal that direction selectivity does not derive from cross-channel coincidence detection but hinges on the amplitudes and activation sequence of auditory nerve inputs tuned to clusters of hotspot frequencies. A simple biophysical model of octopus cells excited with real nerve spike trains recreates direction selectivity through interaction of intrinsic membrane conductances with activation sequence of clustered inputs. We conclude that octopus cells are sequence detectors, sensitive to temporal patterns across cochlear frequency channels. The detection of sequences rather than coincidences is a much simpler but powerful operation to extract temporal information.

scholarly journals Network feedback regulates motor output across a range of modulatory neuron activity

2016 ◽  
Vol 115 (6) ◽  
pp. 3249-3263 ◽  
Author(s):  
Robert M. Spencer ◽  
Dawn M. Blitz
Keyword(s):  
Neuron Activity ◽  
Projection Neurons ◽  
Activity Levels ◽  
Cellular Mechanisms ◽  
Physiological Range ◽  
Network Activation ◽  
Network Output ◽  
The Impact

Modulatory projection neurons alter network neuron synaptic and intrinsic properties to elicit multiple different outputs. Sensory and other inputs elicit a range of modulatory neuron activity that is further shaped by network feedback, yet little is known regarding how the impact of network feedback on modulatory neurons regulates network output across a physiological range of modulatory neuron activity. Identified network neurons, a fully described connectome, and a well-characterized, identified modulatory projection neuron enabled us to address this issue in the crab ( Cancer borealis) stomatogastric nervous system. The modulatory neuron modulatory commissural neuron 1 (MCN1) activates and modulates two networks that generate rhythms via different cellular mechanisms and at distinct frequencies. MCN1 is activated at rates of 5–35 Hz in vivo and in vitro. Additionally, network feedback elicits MCN1 activity time-locked to motor activity. We asked how network activation, rhythm speed, and neuron activity levels are regulated by the presence or absence of network feedback across a physiological range of MCN1 activity rates. There were both similarities and differences in responses of the two networks to MCN1 activity. Many parameters in both networks were sensitive to network feedback effects on MCN1 activity. However, for most parameters, MCN1 activity rate did not determine the extent to which network output was altered by the addition of network feedback. These data demonstrate that the influence of network feedback on modulatory neuron activity is an important determinant of network output and feedback can be effective in shaping network output regardless of the extent of network modulation.

scholarly journals Dopamine regulates distinctively the activity patterns of striatal output neurons in advanced parkinsonian primates

2015 ◽  
Vol 113 (5) ◽  
pp. 1533-1544 ◽  
Author(s):  
Arun Singh ◽  
Li Liang ◽  
Yoshiki Kaneoke ◽  
Xuebing Cao ◽  
Stella M. Papa
Keyword(s):  
Basal Ganglia ◽  
Firing Pattern ◽  
Activity Patterns ◽  
Receptor Activation ◽  
Firing Frequency ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Response Compatible ◽  
Motor Abnormalities ◽  
The Impact

Nigrostriatal dopamine denervation plays a major role in basal ganglia circuitry disarray and motor abnormalities of Parkinson's disease (PD). Studies in rodent and primate models have revealed that striatal projection neurons, namely, medium spiny neurons (MSNs), increase the firing frequency. However, their activity pattern changes and the effects of dopaminergic stimulation in such conditions are unknown. Using single-cell recordings in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates with advanced parkinsonism, we studied MSN activity patterns in the transition to different motor states following levodopa administration. In the “off” state (baseline parkinsonian disability), a burst-firing pattern accompanied by prolonged silences (pauses) was found in 34% of MSNs, and 80% of these exhibited a levodopa response compatible with dopamine D1 receptor activation (direct pathway MSNs). This pattern was highly responsive to levodopa given that bursting/pausing almost disappeared in the “on” state (reversal of parkinsonism after levodopa injection), although this led to higher firing rates. Nonbursty MSNs fired irregularly with marked pausing that increased in the on state in the MSN subset with a levodopa response compatible with dopamine D2 receptor activation (indirect pathway MSNs), although the pause increase was not sustained in some units during the appearance of dyskinesias. Data indicate that the MSN firing pattern in the advanced parkinsonian monkey is altered by bursting and pausing changes and that dopamine differentially and inefficiently regulates these behaviorally correlated patterns in MSN subpopulations. These findings may contribute to understand the impact of striatal dysfunction in the basal ganglia network and its role in motor symptoms of PD.

scholarly journals The influence of the corticothalamic projection on responses in thalamus and cortex

2002 ◽  
Vol 357 (1428) ◽  
pp. 1823-1834 ◽  
Author(s):  
Florentin Wörgötter ◽  
Dirk Eyding ◽  
Jeffrey D. Macklis ◽  
Klaus Funke
Keyword(s):  
Visual Cortex ◽  
Brain Stem ◽  
Afferent Input ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Projection Neurons ◽  
Specific Response ◽  
Cortical Cells ◽  
Corticothalamic Projection ◽  
Corticothalamic Feedback

We review results on the in vivo properties of neurons in the dorsal lateral geniculate nucleus (dLGN) that receives its afferent input from the retina and projects to the visual cortex. In addition, the dLGN receives input from the brain stem and from a rather strong corticothalamic back–projection, which originates in layer 6 of the visual cortex. We compare the behaviour of dLGN cells during spontaneous changes of the frequency contents of the electroencephalograph (EEG) (which are mainly related to a changing brain stem influence), with those that are obtained when experimentally silencing the corticothalamic feedback. The spatial and temporal response properties of dLGN cells are compared during these two conditions, and we report that the neurons behave similarly during a synchronized EEG state and during inactive corticothalamic feedback. In both situations, dLGN cells are rather phasic and their remaining tonic activity is temporally dispersed, indicating a hyperpolarizing effect. By means of a novel method, we were able to chronically eliminate a large proportion of the corticothalamic projection neurons from the otherwise intact cortex. In this condition, we found that cortical cells also lose their EEG specific response differences but, in this instance, probably due to a facilitatory (depolarizing) plasticity reaction of the remaining network.

scholarly journals Multicellular Human Gastric Cancer Spheroids Mimic the Glycosylation Phenotype of Gastric Carcinomas

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2815 ◽  
Author(s):  
Meritxell Balmaña ◽  
Stefan Mereiter ◽  
Francisca Diniz ◽  
Tália Feijão ◽  
Cristina Barrias ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
3D Cell Culture ◽  
Automated Image Analysis ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Model Cell ◽  
Cancer Spheroids ◽  
The Impact

Cellular glycosylation plays a pivotal role in several molecular mechanisms controlling cell–cell recognition, communication, and adhesion. Thus, aberrant glycosylation has a major impact on the acquisition of malignant features in the tumor progression of patients. To mimic these in vivo features, an innovative high-throughput 3D spheroid culture methodology has been developed for gastric cancer cells. The assessment of cancer cell spheroids’ physical characteristics, such as size, morphology and solidity, as well as the impact of glycosylation inhibitors on spheroid formation was performed applying automated image analysis. A detailed evaluation of key glycans and glycoproteins displayed by the gastric cancer spheroids and their counterpart cells cultured under conventional 2D conditions was performed. Our results show that, by applying 3D cell culture approaches, the model cell lines represented the differentiation features observed in the original tumors and the cellular glycocalix underwent striking changes, displaying increased expression of cancer-associated glycan antigens and mucin MUC1, ultimately better simulating the glycosylation phenotype of the gastric tumor.

scholarly journals Inhibition of cholinergic interneurons potentiates corticostriatal transmission in D1 receptor-expressing medium-sized spiny neurons and restores motor learning in parkinsonian condition

2021 ◽  
Author(s):  
Gwenaelle Laverne ◽  
Jonathan Pesce ◽  
Ana Reynders ◽  
Christophe Melon ◽  
Lydia Kerkerian-Le Goff ◽  
...  
Keyword(s):  
Motor Learning ◽  
Long Term Potentiation ◽  
D1 Receptor ◽  
Skill Learning ◽  
D1 Receptors ◽  
Projection Neurons ◽  
Cholinergic Interneurons ◽  
Term Potentiation ◽  
The Impact

Striatal cholinergic interneurons (CINs) respond to salient or reward prediction-related stimuli after conditioning with brief pauses in their activity, implicating them in learning and action selection. This pause is lost in animal models of Parkinson′s disease. How this signal regulates the functioning of the striatum remains an open question. To address this issue, we examined the impact of CIN firing inhibition on glutamatergic transmission between the cortex and the medium-sized spiny projection neurons expressing dopamine D1 receptors (D1 MSNs). Brief interruption of CIN activity had no effect in control condition whereas it increased glutamatergic responses in D1 MSNs after nigrostriatal dopamine denervation. This potentiation was dependent upon M4 muscarinic receptor and protein kinase A. Decreasing CIN firing by opto/chemogenetic strategies in vivo rescued long-term potentiation in some MSNs and alleviated motor learning deficits in parkinsonian mice. Taken together, our findings demonstrate that the control exerted by CINs on corticostriatal transmission and striatal-dependent motor-skill learning depends on the integrity of dopaminergic inputs.

Cadmium ions promote monocytic differentiation of human leukemia HL-60 cells treated with 1α,25-dihydroxyvitamin D3

2010 ◽  
Vol 391 (11) ◽  
Author(s):  
Julia L. Ober-Blöbaum ◽  
Gabriela Engelhardt ◽  
Silke Hebel ◽  
Lothar Rink ◽  
Hajo Haase
Keyword(s):  
Immune System ◽  
Human Leukemia ◽  
Monocytic Differentiation ◽  
Dihydroxyvitamin D3 ◽  
Monocyte Differentiation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Model Cell ◽  
The Impact

AbstractCadmium exposure has multiple effects on the immune system. These can be stimulating, leading to improved clearance of infections, or inhibiting, increasing susceptibility toward infectious agents. Onein vivoobservation in cadmium-exposed individuals is increased monocyte numbers. Therefore, the objective of this study is to investigate the impact of cadmium on monocyte differentiation in the HL-60 model cell line. Administered alone, cadmium had no effect. However, cadmium amplified the expression of monocyte surface markers CD11b and CD14 when differentiation was induced by 1α,25-dihydroxyvitamin D3 (VD3). Furthermore, differentiation with VD3 in the presence of cadmium augmented key monocyte functions: the capacities to perform phagocytosis and generate an oxidative burst. One important signaling pathway required for monocyte differentiation involves extracellular signal-regulated kinase (ERK)1/2. Notably, cadmium induced ERK1/2 phosphorylation in HL-60 cells. Furthermore, U0126, which inhibits ERK1/2 phosphorylation by upstream MAPK/ERK kinases (MEK)1/2, reduced VD3-mediated differentiation and abrogated the effects of cadmium. In conclusion, cadmium can augment monocytic differentiation by activating ERK1/2 signaling, leading to increased generation of functional monocytes. These increased monocyte numbers could contribute to the impact of cadmium on the immune system owing to their role in the production of pro-inflammatory cytokines and activation of T-cells by antigen presentation.

Microcircuitry of the Rostral Nucleus of the Solitary Tract

2017 ◽  
pp. 389-400
Author(s):  
Joseph B. Travers ◽  
Susan P. Travers
Keyword(s):  
Cranial Nerves ◽  
Receptive Fields ◽  
Afferent Input ◽  
Second Order ◽  
Field Size ◽  
Gradual Transition ◽  
Solitary Tract ◽  
Somatosensory Information ◽  
Afferent Fibers ◽  
Rostral Nucleus

Gustatory and somatosensory information from the oral cavity is carried by afferent fibers in the fifth, seventh, and ninth cranial nerves to synapse in the rostral nucleus of the solitary tract (rNST). Incoming taste afferents from the three cranial nerves follow a rostral-caudal gradient within the nucleus, characterized by a gradual transition from neurons with anterior-to-posterior mouth receptive fields. This organization predisposes a pattern of convergence onto second-order neurons of afferents innervating adjacent or apposing receptors, while maintaining an orotopic representation. Although evidence for convergence between the seventh and ninth nerves is relatively infrequent in extracellular recordings, high-magnification confocal microscopy and patch recordings suggest the potential for considerable interaction between these cranial nerves. Overall, the convergence of afferent input functions to increase the overall firing rate, receptive field size, and responsiveness to a wider range of taste stimuli of second-order neurons than peripheral fibers.

scholarly journals Gastric and pyloric motor pattern control by a modulatory projection neuron in the intact crab Cancer pagurus

2011 ◽  
Vol 105 (4) ◽  
pp. 1671-1680 ◽  
Author(s):  
Ulrike B. S. Hedrich ◽  
Florian Diehl ◽  
Wolfgang Stein
Keyword(s):  
Motor Activity ◽  
Motor Pattern ◽  
Central Pattern Generators ◽  
Projection Neuron ◽  
Firing Frequency ◽  
Projection Neurons ◽  
Cycle Period ◽  
Gastric Mill

Neuronal release of modulatory substances provides motor pattern generating circuits with a high degree of flexibility. In vitro studies have characterized the actions of modulatory projection neurons in great detail in the stomatogastric nervous system, a model system for neuromodulatory influences on central pattern generators. Less is known about the activities and actions of modulatory neurons in fully functional and richly modulated network settings, i.e., in intact animals. It is also unknown whether their activities contribute to the motor patterns in different behavioral conditions. Here, we show for the first time the activity and effects of the well-characterized modulatory projection neuron 1 (MCN1) in vivo and compare them to in vitro conditions. MCN1 was always spontaneously active, typically in a rhythmic fashion with its firing being interrupted by ascending inhibitions from the pyloric motor circuit. Its activity contributed to pyloric motor activity, because 1) the cycle period of the motor pattern correlated with MCN1 firing frequency and 2) stimulating MCN1 shortened the cycle period while 3) lesioning of the MCN1 axon reduced motor activity. In addition, gastric mill motor activity was elicited for the duration of the stimulation. Chemosensory stimulation of the antennae moved MCN1 away from baseline activity by increasing its firing frequency. Following this increase, a gastric mill rhythm was elicited and the pyloric cycle period decreased. Lesioning the MCN1 axon prevented these effects. Thus modulatory projection neurons such as MCN1 can control the motor output in vivo, and they participate in the processing of exteroceptive sensory information in behaviorally relevant conditions.

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