scholarly journals Thirst recruits phasic dopamine signaling through subfornical organ neurons

2020 ◽  
Vol 117 (48) ◽  
pp. 30744-30754
Author(s):  
Ted M. Hsu ◽  
Paula Bazzino ◽  
Samantha J. Hurh ◽  
Vaibhav R. Konanur ◽  
Jamie D. Roitman ◽  
...  
Keyword(s):  
Subfornical Organ ◽  
Mesolimbic Dopamine ◽  
First Order ◽  
Glutamatergic Neurons ◽  
Internal Milieu ◽  
Dopamine Signaling ◽  
Goal Directed Behavior ◽  
Peripheral Origin ◽  
Putative Mechanism

Thirst is a highly potent drive that motivates organisms to seek out and consume balance-restoring stimuli. The detection of dehydration is well understood and involves signals of peripheral origin and the sampling of internal milieu by first order homeostatic neurons within the lamina terminalis—particularly glutamatergic neurons of the subfornical organ expressing CaMKIIa (SFOCaMKIIa). However, it remains unknown whether mesolimbic dopamine pathways that are critical for motivation and reinforcement integrate information from these “early” dehydration signals. We used in vivo fiber photometry in the ventral tegmental area and measured phasic dopamine responses to a water-predictive cue. Thirst, but not hunger, potentiated the phasic dopamine response to the water cue. In euvolemic rats, the dipsogenic hormone angiotensin II, but not the orexigenic hormone ghrelin, potentiated the dopamine response similarly to that observed in water-deprived rats. Chemogenetic manipulations of SFOCaMKIIarevealed bidirectional control of phasic dopamine signaling during cued water reward. Taking advantage of within-subject designs, we found predictive relationships between changes in cue-evoked dopamine response and changes in behavioral responses—supporting a role for dopamine in motivation induced by homeostatic need. Collectively, we reveal a putative mechanism for the invigoration of goal-directed behavior: internal milieu communicates to first order, need state-selective circuits to potentiate the mesolimbic dopamine system’s response to cues predictive of restorative stimuli.

scholarly journals Pedunculopontine glutamatergic neurons control spike patterning in substantia nigra dopaminergic neurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Daniel J Galtieri ◽  
Chad M Estep ◽  
David L Wokosin ◽  
Stephen Traynelis ◽  
D James Surmeier
Keyword(s):  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Glutamatergic Synapses ◽  
Glutamatergic Neurons ◽  
Oscillatory Mechanisms ◽  
Goal Directed Behavior ◽  
Stimulation Of

Burst spiking in substantia nigra pars compacta (SNc) dopaminergic neurons is a key signaling event in the circuitry controlling goal-directed behavior. It is widely believed that this spiking mode depends upon an interaction between synaptic activation of N-methyl-D-aspartate receptors (NMDARs) and intrinsic oscillatory mechanisms. However, the role of specific neural networks in burst generation has not been defined. To begin filling this gap, SNc glutamatergic synapses arising from pedunculopotine nucleus (PPN) neurons were characterized using optical and electrophysiological approaches. These synapses were localized exclusively on the soma and proximal dendrites, placing them in a good location to influence spike generation. Indeed, optogenetic stimulation of PPN axons reliably evoked spiking in SNc dopaminergic neurons. Moreover, burst stimulation of PPN axons was faithfully followed, even in the presence of NMDAR antagonists. Thus, PPN-evoked burst spiking of SNc dopaminergic neurons in vivo may not only be extrinsically triggered, but extrinsically patterned as well.

scholarly journals Comparative Study of Chemical Stability of Two H1Antihistaminic Drugs, Terfenadine and ItsIn VivoMetabolite Fexofenadine, Using LC-UV Methods

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Anna Gumieniczek ◽  
Anna Berecka-Rycerz ◽  
Rafał Pietraś ◽  
Izabela Kozak ◽  
Karolina Lejwoda ◽  
...  
Keyword(s):  
Comparative Study ◽  
Chemical Stability ◽  
First Order ◽  
First Order Kinetics ◽  
Kinetics Of Degradation ◽  
Effects Of Temperature ◽  
High Doses ◽  
Antihistaminic Drugs ◽  
Kinetics Of

A comparative study of chemical stability of terfenadine (TER) and itsin vivometabolite fexofenadine (FEX) was performed. Both TER and FEX were subjected to high temperature at different pH and UV/VIS light at different pH and then quantitatively analyzed using new validated LC-UV methods. These methods were used to monitor the degradation processes and to determine the kinetics of degradation for both the compounds. As far as the effects of temperature and pH were concerned, FEX occurred more sensitive to degradation than TER. As far as the effects of UV/VIS light and pH were concerned, the both drugs were similarly sensitive to high doses of light. Using all stress conditions, the processes of degradation of TER and FEX followed the first-order kinetics. The results obtained for these two antihistaminic drugs could be helpful in developing their new derivatives with higher activity and stability at the same time.

Interspike interval dependency from arterial chemoreceptors

1985 ◽  
Vol 59 (5) ◽  
pp. 1566-1570 ◽  
Author(s):  
D. F. Donnelly ◽  
W. F. Nolan ◽  
E. J. Smith ◽  
R. E. Dutton
Keyword(s):  
Carotid Body ◽  
Interspike Interval ◽  
Correlation Coefficients ◽  
Feedback System ◽  
Serial Dependence ◽  
Control Series ◽  
First Order ◽  
System Operating ◽  
Poisson Type

The carotid body impulse generator has been previously characterized as a Poisson-type random process. We examined the validity of this characterization by analyzing sinus nerve spike trains for interspike interval dependency. Fifteen single chemoreceptive afferents were recorded in vivo under hypoxic-hypercapnic conditions, and approximately 1,000 consecutive interspike intervals for each fiber were timed and analyzed for serial dependence. The same set of intervals placed in shuffled order served as a control series without serial dependence. The original spike interval trains showed significantly negative first-order serial correlation coefficients and less variability in joint interval distributions than did the shuffled interval trains. These results suggest that the chemoreceptor afferent train is not random and may reflect a negative feedback system operating within the carotid body that limits variation about a mean frequency.

scholarly journals REGENERATION OF VISUAL PURPLE IN SOLUTION

1939 ◽  
Vol 23 (1) ◽  
pp. 21-39 ◽  
Author(s):  
Aurin M. Chase ◽  
Emil L. Smith
Keyword(s):  
Order Process ◽  
First Order ◽  
Color Changes ◽  
Violet Light ◽  
Frog Retina ◽  
Significant Difference ◽  
Kinetics Of ◽  
Photosensitive Substance ◽  
Subsequent Regeneration

1. Measurements of visual purple regeneration in solution have been made by a procedure which minimized distortion of the results by other color changes so that density changes caused by the regenerating substance alone are obtained. 2. Bleaching a visual purple solution with blue and violet light causes a greater subsequent regeneration than does an equivalent bleaching with light which lacks blue and violet. This is due to a photosensitive substance which has a gradually increasing effective absorption toward the shorter wavelengths. It is uncertain whether this substance is a product of visual purple bleaching or is present in the solution before illumination. 3. The regeneration of visual purple measured at 560 mµ is maximal at about pH 6.7 and decreases markedly at more acid and more alkaline pH's. 4. The absorption spectrum of the regenerating material shows only a concentration change during the course of regeneration, but has a higher absorption at the shorter wavelengths than has visual purple before illumination. 5. Visual purple extractions made at various temperatures show no significant difference in per cent of regeneration. 6. The kinetics of regeneration is usually that of a first order process. Successive regenerations in the same solution have the same velocity constant but form smaller total amounts of regenerated substance. 7. In vivo, the frog retina shows no additional oxygen consumption while visual purple is regenerating.

scholarly journals Forebrain glucocorticoid receptor overexpression alters behavioral encoding of hippocampal CA1 pyramidal cells in mice

2022 ◽  
Author(s):  
Joanna L Spencer-Segal ◽  
Swapnil Gavade ◽  
Qiang Wei ◽  
Colin Johnston ◽  
Savannah Kounelis ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Open Field ◽  
Pyramidal Cells ◽  
Novel Environment ◽  
Ca1 Pyramidal Cells ◽  
Glutamatergic Neurons ◽  
Stress Vulnerability ◽  
Center Location ◽  
Increased Sensitivity

Stress hormone signaling via the glucocorticoid receptor (GR) modulates vulnerability to stress-related disorders, but whether GR influences how the brain encodes contextual experience is unknown. Mice with lifelong GR overexpression in forebrain glutamatergic neurons (GRov) show increased sensitivity to environmental stimuli. This phenotype is developmentally programmed and associated with profound changes in hippocampal gene expression. We hypothesized that GR overexpression influences hippocampal encoding of experiences. To test our hypothesis, we performed in vivo microendoscopic calcium imaging of 1359 dorsal CA1 pyramidal cells in freely behaving male and female WT and GRov mice during exploration of a novel open field. We compared calcium amplitude and event rate as well as sensitivity to center location and mobility between genotypes. GRov neurons exhibited higher average calcium activity than WT neurons in the novel open field. While most neurons showed sensitivity to center location and/or mobility, GRov neurons were more likely to be sensitive to center location and less likely to be sensitive to mobility, as compared to WT neurons. More than one-third of behavior-selective GRov neurons were uniquely sensitive to location without mobility sensitivity; these uniquely center-sensitive neurons were rare in WT. We conclude that dorsal CA1 pyramidal cells in GRov mice show increased activity in a novel environment and preferentially encode emotionally salient behavior. This heightened sensitivity to a novel environment and preferential encoding of emotionally salient elements of experience could underlie differential stress vulnerability in humans with increased glucocorticoid sensitivity.

Quantitative changes in permeability of rat lung epithelium in lung edema

1978 ◽  
Vol 44 (4) ◽  
pp. 576-580 ◽  
Author(s):  
T. H. Gardiner
Keyword(s):  
Slow Component ◽  
Fast Component ◽  
Lung Edema ◽  
Pulmonary Absorption ◽  
Rat Lung ◽  
Lung Epithelium ◽  
Order Component ◽  
First Order ◽  
Quantitative Changes

The pulmonary absorption of 14C-labeled urea, mannitol, inulin, and dextran was measured in vivo in anesthetized rats with alpha-naphthylthiourea (ANTU)-induced (5 mg/kg, ip) lung edema. At 1 h after ANTU treatment, the absorption of mannitol was significantly increased; in 4-h ANTU-treated animals, the absorption of urea was unchanged, whereas the absorption of mannitol, inulin and dextran was increased markedly compared to controls. Although disappearance of each solute from control lungs could be described by a single, first-order rate, absorption time curves for mannitol and inulin showed at least two components in edematous lungs: a fast component(s) and a slower, first-order component; fast-component rates for the two saccharides appeared to be similar; the slow-component rate for each compound was not significantly different from its control rate. The results suggest that fast-component absorption in ANTU-treated rats represents a fraction of instilled solute which entered damaged areas of lung where the porosity of the absorbing membranes was markedly increased, whereas slow-component absorption occurred from normal areas of lung.

scholarly journals ADHD-like behaviors caused by inactivation of a transcription factor controlling the balance of inhibitory and excitatory neuron development in the mouse anterior brainstem

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Francesca Morello ◽  
Vootele Voikar ◽  
Pihla Parkkinen ◽  
Anne Panhelainen ◽  
Marko Rosenholm ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dopaminergic Neurons ◽  
Dopaminergic System ◽  
Developmental Pathways ◽  
Neuron Development ◽  
Learning Deficits ◽  
Glutamatergic Neurons ◽  
Midbrain Dopaminergic Neurons ◽  
Dopamine Signaling ◽  
Neurochemical Changes

Abstract The neural circuits regulating motivation and movement include midbrain dopaminergic neurons and associated inhibitory GABAergic and excitatory glutamatergic neurons in the anterior brainstem. Differentiation of specific subtypes of GABAergic and glutamatergic neurons in the mouse embryonic brainstem is controlled by a transcription factor Tal1. This study characterizes the behavioral and neurochemical changes caused by the absence of Tal1 function. The Tal1cko mutant mice are hyperactive, impulsive, hypersensitive to reward, have learning deficits and a habituation defect in a novel environment. Only minor changes in their dopaminergic system were detected. Amphetamine induced striatal dopamine release and amphetamine induced place preference were normal in Tal1cko mice. Increased dopamine signaling failed to stimulate the locomotor activity of the Tal1cko mice, but instead alleviated their hyperactivity. Altogether, the Tal1cko mice recapitulate many features of the attention and hyperactivity disorders, suggesting a role for Tal1 regulated developmental pathways and neural structures in the control of motivation and movement.

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