scholarly journals Neural Coding of Gustatory Information in the Nucleus of the Solitary Tract in Lean and Obese Awake Freely-licking Rats

2019 ◽  
Author(s):  
Michael S Weiss ◽  
Andras Hajnal ◽  
Krzysztof Czaja ◽  
Patricia M Di Lorenzo
Keyword(s):  
Neural Coding ◽  
Nucleus Tractus Solitarius ◽  
Artificial Saliva ◽  
Single Cells ◽  
High Energy ◽  
Temporal Coding ◽  
Ingestive Behavior ◽  
Taste Perception ◽  
Experimental Chamber ◽  
Compensatory Mechanisms

Taste perception changes with obesity but the underlying neural changes remain poorly understood. To address this issue, we recorded taste responses from single cells in the nucleus tractus solitarius (NTS, the fist central synapse in the gustatory circuit) in awake, diet-induced obese [(DIO; ≥8wks on a high-energy diet (HED)] and lean rats. Rats were implanted with a bundle of microelectrodes in the NTS and allowed to recover. Water-deprived rats were allowed to freely lick various tastants in an experimental chamber. Taste stimuli included an array of sapid stimuli dissolved in artificial saliva (AS). Each taste trial consisted of 5 consecutive licks followed by 5 AS licks presented on a VR5 schedule. Results showed that taste responses in NTS cells in DIO rats (n=49) were smaller in magnitude, shorter in duration and longer in latency that those in lean rats (n=74). However, there were proportionately more taste-responsive cells in DIO than in lean rats. Lick coherence in DIO rats was significantly lower than in lean rats, both in taste-responsive and lick-related cells (n=172 in lean; n=65 in DIO). Analyses of temporal coding showed that taste cells in DIO rats conveyed less information about taste quality than cells in lean rats. Collectively, results suggest that a HED produces blunted, but more prevalent, responses to taste in the NTS and a weakened association of taste responses with ingestive behavior. These neural adaptations may represent both negative effects and compensatory mechanisms of a HED that may underlie deficits in taste-related behavior associated with obesity.

scholarly journals Heterogeneity of neuronal responses in the nucleus of the solitary tract suggests sensorimotor integration in the neural code for taste

2019 ◽  
Vol 121 (2) ◽  
pp. 634-645 ◽  
Author(s):  
Alexander J. Denman ◽  
Joshua D. Sammons ◽  
Jonathan D. Victor ◽  
Patricia M. Di Lorenzo
Keyword(s):  
Neural Coding ◽  
Nucleus Tractus Solitarius ◽  
Motor Behavior ◽  
Artificial Saliva ◽  
Single Cells ◽  
Taste Quality ◽  
Experimental Chamber ◽  
Solitary Tract ◽  
Central Processing ◽  
Awake Rats

Theories of neural coding in the taste system typically rely exclusively on data gleaned from taste-responsive cells. However, even in the nucleus tractus solitarius (NTS), the first stage of central processing, neurons with taste selectivity coexist with neurons whose activity is linked to motor behavior related to ingestion. We recorded from a large ( n = 324) sample of NTS neurons recorded in awake rats, examining both their taste selectivity and the association of their activity with licking. All subjects were implanted with a bundle of microelectrodes aimed at the NTS and allowed to recover. Following moderate water deprivation, rats were placed in an experimental chamber where tastants or artificial saliva (AS) were delivered from a lick spout. Electrophysiological responses were recorded, and waveforms from single cells were isolated offline. Results showed that only a minority of NTS cells responded to taste stimuli as determined by conventional firing-rate measures. In contrast, most cells, including taste-responsive cells, tracked the lick pattern, as evidenced by significant lick coherence in the 5- to 7-Hz range. Several quantitative measures of taste selectivity and lick relatedness showed that the population formed a continuum, ranging from cells dominated by taste responses to those dominated by lick relatedness. Moreover, even neurons whose responses were highly correlated with lick activity could convey substantial information about taste quality. In all, data point to a blurred boundary between taste-dominated and lick-related cells in NTS, suggesting that information from the taste of food and from the movements it evokes are seamlessly integrated. NEW & NOTEWORTHY Neurons in the rostral nucleus of the solitary tract (NTS) are known to encode information about taste. However, recordings from awake rats reveal that only a minority of NTS cells respond exclusively to taste stimuli. The majority of neurons track behaviors associated with food consumption, and even strongly lick-related neurons could convey information about taste quality. These findings suggest that the NTS integrates information from both taste and behavior to identify food.

scholarly journals Enhancing GABAergic Tone in the Rostral Nucleus of the Solitary Tract Reconfigures Sensorimotor Neural Activity

2020 ◽  
Author(s):  
Joshua D. Sammons ◽  
Caroline E. Bass ◽  
Jonathan D. Victor ◽  
Patricia M. Di Lorenzo
Keyword(s):  
Neural Activity ◽  
Inhibitory Activity ◽  
Nucleus Tractus Solitarius ◽  
Artificial Saliva ◽  
Experimental Chamber ◽  
Response Patterns ◽  
Related Activity ◽  
Electrophysiological Recordings ◽  
Rostral Nucleus ◽  
The Relationship

ABSTRACTRecent work has shown that most cells in the rostral, gustatory portion of the nucleus tractus solitarius (rNTS) in awake, freely licking rats show lick-related firing. However, the relationship between taste-related and lick-related activity in rNTS remains unclear. Here, we tested if GABA-derived inhibitory activity regulates the balance of lick- and taste-driven neuronal activity. Combinatorial viral tools were used to restrict expression of ChR2-EYFP to GAD1+ GABAergic neurons. Viral infusions were bilateral in rNTS. 2-4wks later, an optical fiber attached to 8-16 drivable microwires was implanted into the rNTS. After recovery, water-deprived rats were presented with taste stimuli in an experimental chamber. Trials were 5 consecutive taste licks [NaCl, KCl, NH4Cl, sucrose, MSG/IMP, citric acid, quinine, or artificial saliva (AS)] separated by 5 AS licks on a VR5 schedule. Each taste lick triggered a 1s train of laser light (25Hz; 473nm; 8-10mW) in a random half of the trials. In all, 113 cells were recorded in the rNTS, 50 responded to one or more taste stimuli without GABA enhancement. Selective changes in response magnitude (spike count) within cells shifted across unit patterns but preserved inter-stimulus relationships. Cells where enhanced GABAergic tone increased lick coherence conveyed more information distinguishing basic taste qualities and different salts than other cells. In addition, GABA activation significantly amplified the amount of information that discriminated palatable vs. unpalatable tastants. By dynamically regulating lick coherence and remodeling the across-unit response patterns to taste, enhancing GABAergic tone in rNTS reconfigures the neural activity reflecting sensation and movement.Significance StatementThe rostral nucleus tractus solitarius (rNTS) is the first structure in the central gustatory pathway. Electrophysiological recordings from the rNTS in awake, freely-licking animals show that cells in this area have lick- as well as taste-related activity, but the relationship between these characteristics is not well understood. Here, we showed evidence that GABA activation can dynamically regulate both of these two properties in rNTS cells to enhance the information conveyed, especially about palatable vs. unpalatable tastants. These data provide insights into the role of inhibitory activity in the rNTS.

Behavioral analysis of anorexia produced by hindbrain injections of AMPA receptor antagonist NBQX in rats

2002 ◽  
Vol 282 (1) ◽  
pp. R147-R155 ◽  
Author(s):  
Huiyuan Zheng ◽  
Christiane Patterson ◽  
Hans-Rudolf Berthoud
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Burst Size ◽  
Lick Rate ◽  
Ingestive Behavior ◽  
Receptor Subtypes ◽  
General Role ◽  
Motor Processing ◽  
Descending Facilitation ◽  
Response Measures ◽  
Integrative Process

The caudal brain stem integrates short-term feedback signals from the oral cavity and the food-handling abdominal viscera, as well as long-term homeostatic, cognitive, and emotional signals from the forebrain, to control ingestive behavior. Glutamate, acting on various receptor subtypes, plays a prominent role in this integrative process. Fourth ventricular injection of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptor blocker 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo[ f]quinoxaline-7-sulfonamide (NBQX, 0.5–5 nmol/3 μl) dose dependently suppressed intake of 15% sucrose in food-deprived and non-food-deprived rats compared with saline injection. Two consecutive paired NBQX injections (5 nmol) into the fourth ventricle did not produce conditioned taste aversion to saccharin, but LiCl did. Intraburst lick rate and lick efficiency were not affected, but burst size and number and initial lick rate were significantly decreased by NBQX. Local injection of NBQX (2 nmol) into and near the nucleus tractus solitarius also suppressed sucrose intake. These results suggest a general role for non- N-methyl-d-aspartate receptors in the transmission of positive (feedforward) signals, but do not identify the exact processing step involved, such as taste input, sensory-motor processing, or descending facilitation. More localized injections and response measures will be necessary.

scholarly journals ANGI-13. PLEXIN-B2 FACILITATES DIFFUSE GLIOMA INVASION BY REGULATING CELL ADHESION AND ACTO-MYOSIN DYNAMICS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi32-vi32
Author(s):  
Yong Huang ◽  
Rut Tejero ◽  
Vivian Lee ◽  
Chrystian Junqueira Alves ◽  
Ramsey Foty ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Single Cells ◽  
Biomechanical Properties ◽  
Diffuse Glioma ◽  
Compensatory Mechanisms ◽  
Glioma Invasion ◽  
Altered Expression ◽  
Mutant Cells ◽  
Cell Cell

Abstract Diffuse invasion of glioblastoma (GBM) cells into brain tissue is a key factor for its high lethality. GBM cell migration is affected by functions of plexins, which are transmembrane receptors of semaphorins that regulate cell adhesion and cytoskeletal dynamics. Expression of Plexin-B2 is upregulated in GBM and correlates with malignancy. We show here that Plexin-B2 activity regulates biomechanical properties of GBM cells, promoting invasive growth. Plexin-B2 activity increased the capacity of GBM to invade as dispersed single cells by reducing the cell-cell adhesiveness between GBM cells, indicating that a major function of Plexin-B2 activity is to downregulate cell-cell adhesion systems. RNA-Seq analyses also revealed that GBM stem cells (GSC) with deletion of Plexin-B2 altered expression of genes related to cell adhesion and the matrisome, indicating compensatory mechanisms in cellular dynamics. Interestingly, in vivo intracranial transplant studies demonstrated that growth and invasion of Plexin-B2 mutant GSC was impaired, with mutant cells invading shorter distances and migrating mainly as groups of cells forming chains. Plexin-B2 mutant cells also were more likely to adhere to the vasculature, rather than to fiber tracts, suggesting altered biomechanical properties. This shift may be related to high stiffness of basal lamina of the vasculature, as Plexin-B2 KO cells have a preference for migration on stiff substrate in vitro. Intriguingly, the loss in Plexin-B2 expression also changed the distribution of the mechanosensor transction factor YAP, with high expression of Plexin-B2 correlating with increased nuclear YAP. Structure-function analyses revealed that the Ras-GAP domain as main signaling output of Plexin-B2. The Rap proteins are pleiotropic regulators of cell adhesion and actomysosin contractility. Our data also showed that overexpression of Plexin-B2 can lead to decreased levels of Rap1/Rap2. Thus, Plexin-B2 acts as a key regulator of the adhesion and contractility of GBM cells, thereby facilitating their diffuse invasion.

Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling before obesity onset

2004 ◽  
Vol 286 (1) ◽  
pp. R143-R150 ◽  
Author(s):  
Barry E. Levin ◽  
Ambrose A. Dunn-Meynell ◽  
William A. Banks
Keyword(s):  
Blood Brain Barrier ◽  
Leptin Receptor ◽  
Nucleus Tractus Solitarius ◽  
High Energy ◽  
Brain Barrier ◽  
Leptin Signaling ◽  
Caloric Density ◽  
Diet Induced Obesity ◽  
Blood Brain ◽  
Arcuate Nuclei

Rats selectively bred to develop diet-induced obesity (DIO) were compared with those bred to be diet resistant (DR) on a 31% fat high-energy diet with regard to their central leptin signaling and blood-brain barrier (BBB) transport. Peripheral leptin injection (15 mg/kg ip) into lean 4- to 5-wk-old rats produced 54% less anorexia in DIO than DR rats. DIO rats also had 21, 63, and 64% less leptin-induced immunoreactive phosphorylated signal transducer and activator of transcription 3 (pSTAT3) expression in the hypothalamic arcuate, ventromedial, and dorsomedial nuclei, respectively. However, hindbrain leptin-induced nucleus tractus solitarius pSTAT3 and generalized sympathetic (24-h urine norepinephrine) activation were comparable. Reduced central leptin signaling was not due to defective BBB transport since transport did not differ between lean 4- to 5-wk-old DIO and DR rats. Conversely, DIO leptin BBB transport was reduced when they became obese at 23 wk of age on low-fat chow or after 6 wk on high-energy diet. In addition, leptin receptor mRNA expression was 23% lower in the arcuate nuclei of 4- to 5-wk-old DIO compared with DR rats. Thus a preexisting reduction in hypothalamic but not brain stem leptin signaling might contribute to the development of DIO when dietary fat and caloric density are increased. Defects in leptin transport appear to be an acquired defect associated with the development of obesity and possibly age.

scholarly journals A Unique Prototypic Device for Radiation Therapy: The p53-Independent Antiproliferative Effect of Neutron Radiation

Acta Naturae ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 99-102 ◽  
Author(s):  
D. I. Yurkov ◽  
S. V. Syromukov ◽  
V. V. Tatarskiy ◽  
E. S. Ivanova ◽  
A. I. Khamidullina ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
P53 Protein ◽  
Single Cells ◽  
Human Tumor ◽  
Neutron Radiation ◽  
High Energy ◽  
Antiproliferative Effect ◽  
Heavy Particles ◽  
M Phase ◽  
The Status

Radiation therapy with heavy particles including neutrons, an otherwise therapeutically perspective because of its high tissue penetration and efficient tumor damage, is currently limited by the lack of adequate equipment. An NG-24 generator (140 kg, 42 110 cm, ~1011 particles/s, 14 MeV) has been designed and engineered to replace the huge and environmentally harmful neutron reactors, cyclotrons, and accelerators with a compact, portable, safe, and potent source of high-energy neutrons. We demonstrate that the neutron beam produced by NG-24 causes a significant antiproliferative effect on human tumor cell lines regardless of the status of the anti-apoptotic p53 protein. Phosphorylation of histone 2A and increased amounts of p21, cyclin D, and phospho-p53 were detectable in HCT116 colon carcinoma cells (wild-type p53) irradiated with 4 Gy several days post-treatment, accompanied by G2/M phase arrest. These treatments dramatically reduced the ability of single cells to form colonies. In the HCT116p53KO subline (p53 -/-), the G2/M arrest was independent of the aforementioned mechanisms. Hence, the NG-24 generator is a source of a powerful, therapeutically relevant neutron flux that triggers a p53-independent antiproliferative response in tumor cells.

scholarly journals Temporal Coding of Intensity of NaCl and HCl in the Nucleus of the Solitary Tract of the Rat

2011 ◽  
Vol 105 (2) ◽  
pp. 697-711 ◽  
Author(s):  
Jen-Yung Chen ◽  
Jonathan D. Victor ◽  
Patricia M. Di Lorenzo
Keyword(s):  
Single Cells ◽  
Temporal Structure ◽  
Relative Size ◽  
Spike Timing ◽  
Temporal Coding ◽  
Spike Count ◽  
Scaling Analysis ◽  
Solitary Tract ◽  
Stimulus Quality ◽  
Temporal Characteristics

Sensory neurons are generally tuned to a subset of stimulus qualities within their sensory domain and manifest this tuning by the relative size of their responses to stimuli of equal intensity. However, response size alone cannot unambiguously signal stimulus quality, since response size also depends on stimulus intensity. Thus a common problem faced by sensory systems is that response size (e.g., spike count) confounds stimulus quality and intensity. Here, using the gustatory system as a model, we asked whether temporal firing characteristics could disambiguate these axes. To address this question, we recorded taste responses of single neurons in the nucleus of the solitary tract (NTS, the first central gustatory relay) in anesthetized rats to a range of concentrations of NaCl and HCl and their binary mixtures. To assess the contribution of the temporal characteristics of the response to discrimination among tastants, a family of metrics that quantifies the similarity of two spike trains in terms of spike count and spike timing was used. Results showed that the spike count produced by different taste qualities and different concentrations overlapped in most cells, implying that information conveyed by spike count is imprecise. Multidimensional scaling analysis of taste responses using similarity of temporal characteristics showed that different taste qualities, intensities, and mixtures formed distinct clusters in this “temporal coding” taste space and were arranged in a logical order. Thus the temporal structure of taste responses in single cells in the NTS can simultaneously convey information about both taste quality and intensity.

Chaos and neural coding: Is the binding problem a pseudo-problem?

2001 ◽  
Vol 24 (5) ◽  
pp. 826-827 ◽  
Author(s):  
Antonino Raffone ◽  
Cees van Leeuwen
Keyword(s):  
Neural Coding ◽  
Temporal Coding ◽  
Binding Problem ◽  
Holistic View ◽  
Brain Functions ◽  
Visual Scenes ◽  
Thoughtful Discussion ◽  
Formal Properties

Tsuda's article suggests several plausible concepts of neurodynamic representation and processing, with a thoughtful discussion of their neurobiological grounding and formal properties. However, Tsuda's theory leads to a holistic view of brain functions and to the controversial conclusion that the “binding problem” is a pseudo-problem. By contrast, we stress the role of chaotic patterns in solving the binding problem, in terms of flexible temporal coding of visual scenes through graded and intermittent synchrony.

scholarly journals Neural Coding of Spatial Phase in V1 of the Macaque Monkey

2003 ◽  
Vol 89 (6) ◽  
pp. 3304-3327 ◽  
Author(s):  
Dmitriy Aronov ◽  
Daniel S. Reich ◽  
Ferenc Mechler ◽  
Jonathan D. Victor
Keyword(s):  
Metric Space ◽  
Neural Coding ◽  
Macaque Monkey ◽  
Temporal Coding ◽  
Phase Coding ◽  
Spatial Phase ◽  
Novel Approach ◽  
Phase Cycle ◽  
The Times ◽  
Temporal Profiles

We examine the responses of single neurons and pairs of neurons, simultaneously recorded with a single tetrode in the primary visual cortex of the anesthetized macaque monkey, to transient presentations of stationary gratings of varying spatial phase. Such simultaneously recorded neurons tended to have similar tuning to the phase of the grating. To determine the response features that reliably discriminate these stimuli, we use the metric-space approach extended to pairs of neurons. We find that paying attention to the times of individual spikes, at a resolution of ∼30 ms, and keeping track of which neuron fires which spike rather than just the summed local activity contribute substantially to phase coding. The contribution is both quantitative (increasing the fidelity of phase coding) and qualitative (enabling a 2-dimensional “response space” that corresponds to the spatial phase cycle). We use a novel approach, the extraction of “temporal profiles” from the metric space analysis, to interpret and compare temporal coding across neurons. Temporal profiles were remarkably consistent across a large subset of neurons. This consistency indicates that simple mechanisms (e.g., comparing the size of the transient and sustained components of the response) allow the temporal contribution to phase coding to be decoded.

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