scholarly journals PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation

2015 ◽  
Vol 309 (8) ◽  
pp. R795-R804 ◽  
Author(s):  
Stefan Trapp ◽  
Simon C. Cork
Keyword(s):  
Energy Balance ◽  
Brain Stem ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Receptor Activation ◽  
Vagal Afferents ◽  
Reticular Nucleus ◽  
Autonomic Neurons ◽  
The Brain

Within the brain, glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Additionally, GLP-1 influences the mesolimbic reward system to modulate the rewarding properties of palatable food. GLP-1 is produced in the gut and by hindbrain preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarii (NTS) and medullary intermediate reticular nucleus. Transgenic mice expressing glucagon promoter-driven yellow fluorescent protein revealed that PPG neurons not only project to central autonomic control regions and mesolimbic reward centers, but also strongly innervate spinal autonomic neurons. Therefore, these brain stem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to sympathetic preganglionic neurons. Electrical recordings from PPG neurons in vitro have revealed that they receive synaptic inputs from vagal afferents entering via the solitary tract. Vagal afferents convey satiation to the brain from signals like postprandial gastric distention or activation of peripheral GLP-1 receptors. CCK and leptin, short- and long-term satiety peptides, respectively, increased the electrical activity of PPG neurons, while ghrelin, an orexigenic peptide, had no effect. These findings indicate that satiation is a main driver of PPG neuronal activation. They also show that PPG neurons are in a prime position to respond to both immediate and long-term indicators of energy and feeding status, enabling regulation of both energy balance and general autonomic homeostasis. This review discusses the question of whether PPG neurons, rather than gut-derived GLP-1, are providing the physiological substrate for the effects elicited by central nervous system GLP-1 receptor activation.

Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

2008 ◽  
Vol 294 (3) ◽  
pp. R905-R914 ◽  
Author(s):  
Guadalupe Perfume ◽  
Sabrina L. Nabhen ◽  
Karla Riquelme Barrera ◽  
María G. Otero ◽  
Liliana G. Bianciotti ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Cardiovascular Effects ◽  
Receptor Activation ◽  
Catecholaminergic Neurons ◽  
Endothelin System ◽  
Catecholaminergic Transmission ◽  
Underlying Mechanisms ◽  
G Protein Coupled ◽  
The Brain

Brain catecholamines are involved in the regulation of biological functions, including cardiovascular activity. The hypothalamus presents areas with high density of catecholaminergic neurons and the endothelin system. Two hypothalamic regions intimately related with the cardiovascular control are distinguished: the anterior (AHR) and posterior (PHR) hypothalamus, considered to be sympathoinhibitory and sympathoexcitatory regions, respectively. We previously reported that endothelins (ETs) are involved in the short-term tyrosine hydroxylase (TH) regulation in both the AHR and PHR. TH is crucial for catecholaminergic transmission and is tightly regulated by well-characterized mechanisms. In the present study, we sought to establish the effects and underlying mechanisms of ET-1 and ET-3 on TH long-term modulation. Results showed that in the AHR, ETs decreased TH activity through ETB receptor activation coupled to the nitric oxide, phosphoinositide, and CaMK-II pathways. They also reduced total TH level and TH phosphorylated forms (Ser 19 and 40). Conversely, in the PHR, ETs increased TH activity through a G protein-coupled receptor, likely an atypical ET receptor or the ETC receptor, which stimulated the phosphoinositide and adenylyl cyclase pathways, as well as CaMK-II. ETs also increased total TH level and the Ser 19, 31, and 40 phosphorylated sites of the enzyme. These findings support that ETs are involved in the long-term regulation of TH activity, leading to reduced sympathoinhibition in the AHR and increased sympathoexcitation in the PHR. Present and previous studies may partially explain the cardiovascular effects produced by ETs when applied to the brain.

scholarly journals Computational Studies on Acquisition and Adaptation of Ocular Following Responses Based on Cerebellar Synaptic Plasticity

2002 ◽  
Vol 87 (3) ◽  
pp. 1554-1571 ◽  
Author(s):  
Kenji Yamamoto ◽  
Yasushi Kobayashi ◽  
Aya Takemura ◽  
Kenji Kawano ◽  
Mitsuo Kawato
Keyword(s):  
Synaptic Plasticity ◽  
Brain Stem ◽  
Visual Motion ◽  
Climbing Fiber ◽  
Inhibitory Synapses ◽  
Ocular Following ◽  
Mst Neurons ◽  
P Cells ◽  
The Brain

To investigate how cerebellar synaptic plasticity guides the acquisition and adaptation of ocular following response (OFR), a large-scale network model was developed. The model includes the cerebral medial superior temporal area (MST), Purkinje cells (P cells) of the ventral paraflocculus, the accessory optic and climbing fiber systems, the brain stem oculomotor network, and the oculomotor plant. The model reconstructed temporal profiles of both firing patterns of MST neurons and P cells and eye movements. Model MST neurons ( n = 1,080) were set to be driven by retinal error and exhibited 12 preferred directions, 30 preferred velocities, and 3 firing waveforms. Correspondingly, each model P cell contained 1,080 excitatory synapses from granule cell axons (GCA) and 1,080 inhibitory synapses. P cells ( n = 40) were classified into four groups by their laterality (hemisphere) and by preferred directions of their climbing fiber inputs (CF) (contralateral or upward). The brain stem neural circuit and the oculomotor plant were modeled on the work of Yamamoto et al. The initial synaptic weights on the P cells were set randomly. At the beginning, P cell simple spikes were not well modulated by visual motion, and the eye was moved only slightly by the accessory optic system. The synaptic weights were updated according to integral-differential equation models of physiologically demonstrated synaptic plasticity: long-term depression and long-term potentiation for GCA synapses and rebound potentiation for inhibitory synapses. We assumed that maximum plasticity was induced when GCA inputs preceded CF inputs by 200 ms. After more than 10,000 presentations of ramp-step visual motion, the strengths of both the excitatory and inhibitory synapses were modified. Subsequently, the simple spike responses became well developed, and ordinary OFRs were acquired. The preferred directions of simple spikes became the opposite of those of CFs. Although the model MST neurons were set to possess a wide variety of firing characteristics, the model P cells acquired only downward or ipsilateral preferred directions, high preferred velocities and stereotypical firing waveforms. Therefore the drastic transition of the neural representation from the population codes in the MST to the firing-rate codes of simple spikes were learned at the GCA-P cell synapses and inhibitory cells-P cell synapses. Furthermore, the model successfully reproduced the gain- and directional-adaptation of OFR, which was demonstrated by manipulating the velocity and direction of visual motion, respectively. When we assumed that synaptic plasticity could only occur if CF inputs preceded GCA inputs, the ordinary OFR were acquired but neither the gain-adaptation nor the directional adaptation could be reproduced.

scholarly journals Retrograde Transport of Transcription Factor NF-κB in Living Neurons

2000 ◽  
Vol 276 (15) ◽  
pp. 11821-11829 ◽  
Author(s):  
Henning Wellmann ◽  
Barbara Kaltschmidt ◽  
Christian Kaltschmidt
Keyword(s):  
Transcription Factor ◽  
Green Fluorescent Protein ◽  
Fluorescent Protein ◽  
Retrograde Transport ◽  
Receptor Activation ◽  
Transcriptional Changes ◽  
Localization Signal ◽  
Green Fluorescent ◽  
Living Neurons

The mechanism by which signals such as those produced by glutamate are transferred to the nucleus may involve direct transport of an activated transcription factor to trigger long-term transcriptional changes. Ionotropic glutamate receptor activation or depolarization activates transcription factor NF-κB and leads to translocation of NF-κB from the cytoplasm to the nucleus. We investigated the dynamics of NF-κB translocation in living neurons by tracing the NF-κB subunit RelA (p65) with jellyfish green fluorescent protein. We found that green fluorescent protein-RelA was located in either the nucleus or cytoplasm and neurites, depending on the coexpression of the cognate inhibitor of NF-κB, IκB-α. Stimulation with glutamate, kainate, or potassium chloride resulted in a redistribution of NF-κB from neurites to the nucleus. This transport depended on an intact nuclear localization signal on RelA. Thus, in addition to its role as a transcription factor, NF-κB may be a signal transducer, transmitting transient glutamatergic signals from distant sites to the nucleus.

Effects of insulin on the cardiovascular integrating mechanisms of brain stem in cats

1993 ◽  
Vol 265 (4) ◽  
pp. E609-E616 ◽  
Author(s):  
S. W. Kuo ◽  
J. H. Hsieh ◽  
W. C. Wu ◽  
H. T. Horng ◽  
L. R. Shian ◽  
...  
Keyword(s):  
Brain Stem ◽  
Cardiovascular Responses ◽  
Serum Glucose ◽  
Ventrolateral Medulla ◽  
Reticular Nucleus ◽  
Motor Nucleus ◽  
Renal Nerve ◽  
Pressor Responses ◽  
The Brain ◽  
Stimulation Of

In 65 cats anesthetized with alpha-chloralose and urethane, the effects of insulin on cardiovascular responses to stimulation of various structures in the brain stem were studied. The threshold dose of insulin injected intravenously that produced systemic hypoglycemia was 5-10 U/kg. Subthreshold hypoglycemic doses of insulin were used intracerebroventricularly (0.25 U/kg) or intracerebrally (2 mU in 200 nl). Sixty minutes after intravenous insulin, when serum glucose concentrations decreased from 158 to 43 mg/100 ml, pressor responses to stimulation of the periaqueductal gray of midbrain (PAG), locus coeruleus (LC), dorsal medulla (DM), ventrolateral medulla (VLM), and parvocellular reticular nucleus (PVC) decreased significantly. Depressor and bradycardiac response to stimulation of paramedian reticular nucleus or dorsal motor nucleus of vagus (DMV) decreased significantly as well. Thirty minutes after intracerebroventricular insulin, pressor responses of PAG, DM, and the bradycardiac response of DMV decreased significantly. Thirty minutes after intracerebral insulin, pressor responses and renal nerve activities of LC (but not PAG), VLM, DM, and PVC decreased significantly. A similar but faster onset (5 min) of depression of cardiovascular responses on stimulating the LC, VLM, DM, and PVC was observed in another six acutely midcollicular-decerebrate cats recovered from halothane anesthesia. These findings suggest that insulin directly inhibits the vasomotor structures of the brain stem and decreases the pressor responses to stimulation.

Participation of RGS8 in the ternary complex of agonist, receptor and G-protein

2004 ◽  
Vol 32 (6) ◽  
pp. 1045-1047 ◽  
Author(s):  
A. Benians ◽  
M. Nobles ◽  
A. Tinker
Keyword(s):  
G Protein ◽  
Ternary Complex ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Receptor Activation ◽  
K Channel ◽  
Physical Interaction ◽  
Rgs Proteins ◽  
Α Subunit ◽  
G Protein Α Subunit

The RGS (regulators of G-protein signalling) protein family sharpen signalling kinetics through heterotrimeric G-proteins by enhancing the GTPase activity of the G-protein α subunit. Paradoxically, they also accelerate receptor-stimulated activation. We investigated this paradox using the cloned G-protein gated K+ channel as a reporter of the G-protein cycle, and FRET (fluorescence resonance energy transfer) between cyan and yellow fluorescent protein tagged proteins to detect physical interactions. Our results with the neuronal protein, RGS8, show that the enhancement of activation kinetics is a variable phenomenon determined by receptor type, G-protein isoform and RGS8 expression levels. In contrast, deactivation was consistently accelerated after removal of agonist. FRET microscopy revealed a stable physical interaction between RGS8-yellow fluorescent protein and Go αA-cyan fluorescent protein that occurred in the presence and absence of receptor activation and was not competed away by Gβγ overexpression. FRET was also seen between RGS8 and Gγ, demonstrating that RGS8 binds to the heterotrimeric G-protein as well as G-protein α subunit-GTP and the transition complex. We propose a novel model for the action of RGS proteins on the G-protein cycle involving participation of the RGS in the ternary complex: for certain combinations of agonist, receptor and G-protein, RGS8 expression improves upon the ‘kinetic efficacy’ of G-protein activation.

Differential Effects of the Reticulospinal System on Locomotion in Lamprey

1998 ◽  
Vol 80 (1) ◽  
pp. 103-112 ◽  
Author(s):  
T. Wannier ◽  
T. G. Deliagina ◽  
G. N. Orlovsky ◽  
S. Grillner
Keyword(s):  
Spinal Cord ◽  
Brain Stem ◽  
Reticular Formation ◽  
Reticular Nucleus ◽  
Caudal Part ◽  
Ventral Roots ◽  
Reticular Nuclei ◽  
The Brain ◽  
Rostral Part ◽  
Different Parts

Wannier, T., T. G. Deliagina, G. N. Orlovsky, and S. Grillner. Differential effects of the reticulospinal system on locomotion in lamprey. J. Neurophysiol. 80: 103–112, 1998. Specific effects of stimulating different parts of the reticulospinal (RS) system on the spinal locomotor pattern are described in lamprey. In the in vitro brain stem and spinal cord preparation, microstimulation in different areas of the reticular formation was performed by ejecting a small amount of d-glutamate from a micropipette. These areas were distributed over the four reticular nuclei of the brain stem: the mesencephalic reticular nucleus (MRN) and the anterior, middle and posterior rhombencephalic reticular nuclei (ARRN, MRRN, and PRRN, respectively). To prevent synaptic spread of excitation within the brain stem, the synaptic transmission was blocked by using a low Ca2+, high Mn2+ physiological saline in the brain stem pool. “Fictive” locomotion was evoked by applying N-methyl-d-aspartate (NMDA) to the spinal cord. Rhythmical discharges of motoneurons were recorded bilaterally in the midbody area, from the ventral roots that had been subdivided in dorsal and ventral branches, supplying the dorsal and ventral part of the myotome, respectively. Two major effects of brain stem stimulation were elicited: a change in the frequency of the locomotory rhythm and an induction of asymmetry (left/right, dorsal/ventral) in the segmental motor output. Approximately 50% of the stimulated sites evoked a change in locomotor frequency. In the PRRN almost all effective sites evoked an increase in frequency (10–50%). In the other nuclei, increase and decrease (10–30%) were observed equally frequently. Most of the stimulated sites (50–80%) in any reticular nucleus evoked asymmetry in the segmental motor output. Distortion of the segmental output symmetry was classified into eight categories by comparing the intensity of locomotor bursts in the dorsal and ventral branches of the two ventral roots, ipsilateral and contralateral to the stimulated side. These categories differed in the direction of the body flexion, which would be evoked during normal swimming: ipsilateral (I), contralateral (C), dorsal (D), ventral (V), ipsilateral and dorsal (ID), ipsilateral and ventral (IV), contralateral and dorsal (CD), and contralateral and ventral (CV). The different categories were not equally represented in each nucleus and across the nuclei. The most pronounced categories for each nucleus were as follow. In MRN: I (33%); ARRN: C (44%); MRRN: rostral part, I (36%) and caudal part, CV (42%); and PRRN: rostral part, I (40%) and caudal part, IV (35%). Other categories were also present but less common in each nucleus. To examine if the effects of brain stem stimulation were uniform along the spinal cord, recordings were performed from distal parts of the cord. Stimulation of a given point in the brain stem produced similar pattern of effects in 59% of cases and different patterns in 41% of cases. The main conclusion of the present study is that the proportion of RS neurons with different influences on the spinal locomotor network differs significantly among different parts of the reticular formation of the lamprey. The specificity of RS influences may represent a basis for modifications of the segmental locomotor output necessary for the control of equilibrium and steering during locomotion.

scholarly journals Muscarinic Receptor Activation Elicits Sustained, Recurring Depolarizations in Reticulospinal Neurons

2007 ◽  
Vol 97 (5) ◽  
pp. 3181-3192 ◽  
Author(s):  
R. W. Smetana ◽  
S. Alford ◽  
R. Dubuc
Keyword(s):  
Brain Stem ◽  
Muscarinic Receptor ◽  
Central Pattern Generators ◽  
Receptor Activation ◽  
Motor Output ◽  
Reticular Nucleus ◽  
Muscarinic Agonists ◽  
Bath Application ◽  
Descending Input ◽  
Pattern Generators

In lampreys, brain stem reticulospinal (RS) neurons constitute the main descending input to the spinal cord and activate the spinal locomotor central pattern generators. Cholinergic nicotinic inputs activate RS neurons, and consequently, induce locomotion. Cholinergic muscarinic agonists also induce locomotion when applied to the brain stem of birds. This study examined whether bath applications of muscarinic agonists could activate RS neurons and initiate motor output in lampreys. Bath applications of 25 μM muscarine elicited sustained, recurring depolarizations (mean duration of 5.0 ± 0.5 s recurring with a mean period of 55.5 ± 10.3 s) in intracellularly recorded rhombencephalic RS neurons. Calcium imaging experiments revealed that muscarine induced oscillations in calcium levels that occurred synchronously within the RS neuron population. Bath application of TTX abolished the muscarine effect, suggesting the sustained depolarizations in RS neurons are driven by other neurons. A series of lesion experiments suggested the caudal half of the rhombencephalon was necessary. Microinjections of muscarine (75 μM) or the muscarinic receptor (mAchR) antagonist atropine (1 mM) lateral to the rostral pole of the posterior rhombencephalic reticular nucleus induced or prevented, respectively, the muscarinic RS neuron response. Cells immunoreactive for muscarinic receptors were found in this region and could mediate this response. Bath application of glutamatergic antagonists (6-cyano-7-nitroquinoxaline-2,3-dione/d-2-amino-5-phosphonovaleric acid) abolished the muscarine effect, suggesting that glutamatergic transmission is needed for the effect. Ventral root recordings showed spinal motor output coincides with RS neuron sustained depolarizations. We propose that unilateral mAchR activation on specific cells in the caudal rhombencephalon activates a circuit that generates synchronous sustained, recurring depolarizations in bilateral populations of RS neurons.

Anatomy and physiology of saccadic long-lead burst neurons recorded in the alert squirrel monkey. I. Descending projections from the mesencephalon

1996 ◽  
Vol 76 (1) ◽  
pp. 332-352 ◽  
Author(s):  
C. A. Scudder ◽  
A. K. Moschovakis ◽  
A. B. Karabelas ◽  
S. M. Highstein
Keyword(s):  
Superior Colliculus ◽  
Brain Stem ◽  
Reticular Formation ◽  
Discharge Pattern ◽  
Reticular Nucleus ◽  
Medullary Reticular Formation ◽  
Burst Neurons ◽  
Nucleus Reticularis ◽  
Efferent Neurons ◽  
The Brain

1. The intra-axonal recording and horseradish peroxidase injection technique together with spontaneous eye movement monitoring has been employed in alert behaving monkeys to study the discharge pattern and axonal projections of mesencephalic saccade-related long-lead burst neurons (LLBNs). 2. Most of the recovered axons (N = 21) belonged to two classes of neurons. The majority (N = 13) were identified as efferents of the superior colliculus and had circumscribed movement fields typical of collicular saccade-related burst neurons. This discharge pattern, their responses to electrical stimulation of one or both superior colliculi, and their morphological appearance identified them as members of the T class of tectal efferent neurons. 3. Axons of these T cells deployed terminal fields within several saccade-related brain stem areas including the nucleus reticularis tegmenti pontis, which projects to the cerebellum; the nucleus reticularis pontis oralis and caudalis, which contains excitatory premotor burst neurons; the nucleus raphe interpositus, which contains omnipause neurons; the nucleus paragigantocellularis, which contains inhibitory premotor burst neurons, as well as other less differentiated parts of the brain stem reticular formation. 4. The other class of LLBNs (N = 4) had their somata in the medullary reticular formation just lateral to the interstitial nucleus of Cajal. They projected primarily to the raphe nuclei, the medullary reticular formation, and the paramedian reticular nucleus. Discharges were of the directional type with up ON directions (N = 3) and down ON directions (N = 1). 5. Other fibers, which project to pontine and medullary oculomotor structures but whose somata were not recovered (N = 4), illustrate that there are also other types of LLBNs that contribute to the generation and control of saccadic eye movements. 6. Our findings complement previous data about the axonal trajectories of T-type superior colliculus efferents. They also demonstrate the existence of LLBNs located in the mesencephalic reticular formation and their target areas in the brain stem. Implications of these findings for current concepts of oculomotor control are discussed.

Glutamate activation of neurons in CV-reactive areas of cat brain stem affects urinary bladder motility

1993 ◽  
Vol 265 (4) ◽  
pp. F520-F529 ◽  
Author(s):  
S. Y. Chen ◽  
S. D. Wang ◽  
C. L. Cheng ◽  
J. S. Kuo ◽  
W. C. De Groat ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Brain Stem ◽  
Locus Ceruleus ◽  
Ventrolateral Medulla ◽  
Reticular Nucleus ◽  
Motor Nucleus ◽  
Arterial Blood ◽  
Dorsal Motor Nucleus ◽  
The Brain ◽  
Stimulation Of

To investigate the interaction between cardiovascular (CV)-reactive areas in the brain stem and urinary bladder (UB) motility, 48 adult cats of either sex were anesthetized intraperitoneally with alpha-chloralose (40 mg/kg) and urethan (400 mg/kg). The changes of UB motility and systemic arterial blood pressure (SAP) were produced by microinjection of sodium glutamate (0.5 M, 100-200 nl) into the pressor, depressor, or vagobradycardiac areas of the brain stem. Stimulation of these CV-reactive areas increased or decreased UB motility. Areas that produced an increase in UB motility listed in decreasing order of effectiveness are locus ceruleus-parabrachial nucleus in the pons, dorsal medulla, dorsal motor nucleus of vagus, and ventrolateral medulla. Areas eliciting a decrease in UB motility listed in decreasing order are gigantocellular tegmental field, parvocellular reticular nucleus, and ambiguus nucleus. Stimulation of other pressor sites in medulla also increased UB motility. Activation of the paramedian reticular nucleus, which consistently produced depressor responses, and activation of raphe nuclei, which produced depressor or pressor responses, consistently decreased UB motility. The integrity of the vagus nerve was not essential for the UB response to brain stimulation. These findings indicate that neuronal mechanisms for controlling UB and CV functions coexist at many sites in the brain stem. At those sites that commonly produce changes in UB motility, the type of UB response (excitation or inhibition) was in the same direction as the change of SAP. However, at some sites responses were inverse. It is not known whether the responses of the UB and CV system are controlled by common or separate populations of neurons at these sites.

scholarly journals Sex-steroid-dependent plasticity of brain-stem autonomic circuits

2020 ◽  
Vol 319 (1) ◽  
pp. R60-R68
Author(s):  
Erica L. Littlejohn ◽  
Stephanie Fedorchak ◽  
Carie R. Boychuk
Keyword(s):  
Nervous System ◽  
Brain Stem ◽  
Sex Hormones ◽  
Nucleus Tractus Solitarius ◽  
Critical Role ◽  
Vagal Afferents ◽  
Motor Nucleus ◽  
Peripheral Sensory ◽  
The Brain

In the central nervous system (CNS), nuclei of the brain stem play a critical role in the integration of peripheral sensory information and the regulation of autonomic output in mammalian physiology. The nucleus tractus solitarius of the brain stem acts as a relay center that receives peripheral sensory input from vagal afferents of the nodose ganglia, integrates information from within the brain stem and higher central centers, and then transmits autonomic efferent output through downstream premotor nuclei, such as the nucleus ambiguus, the dorsal motor nucleus of the vagus, and the rostral ventral lateral medulla. Although there is mounting evidence that sex and sex hormones modulate autonomic physiology at the level of the CNS, the mechanisms and neurocircuitry involved in producing these functional consequences are poorly understood. Of particular interest in this review is the role of estrogen, progesterone, and 5α-reductase-dependent neurosteroid metabolites of progesterone (e.g., allopregnanolone) in the modulation of neurotransmission within brain-stem autonomic neurocircuits. This review will discuss our understanding of the actions and mechanisms of estrogen, progesterone, and neurosteroids at the cellular level of brain-stem nuclei. Understanding the complex interaction between sex hormones and neural signaling plasticity of the autonomic nervous system is essential to elucidating the role of sex in overall physiology and disease.

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