Taste activity in the parabrachial region in adult rats following neonatal chorda tympani transection

Journal of Neurophysiology ◽

10.1152/jn.00552.2020 ◽

2021 ◽

Author(s):

Louis J Martin ◽

Joseph M. Breza ◽

Suzanne Sollars

Keyword(s):

Parabrachial Nucleus ◽

Chorda Tympani ◽

Neural Responses ◽

Functional Plasticity ◽

Adult Rats ◽

High Preference ◽

Gustatory Nerve ◽

Evoked Activity ◽

The Impact

The chorda tympani is a gustatory nerve that nerve fails to regenerate if sectioned in rats 10 days of age or younger. This early denervation causes an abnormally high preference for NH4Cl in adult rats, but the impact of neonatal chorda tympani transection on the development of the gustatory hindbrain is unclear. Here, we tested the effect of neonatal chorda tympani transection (CTX) on gustatory responses in the parabrachial nucleus (PbN). We recorded in vivo extracellular spikes in single PbN units of urethane-anesthetized adult rats following CTX at P5 (chronic CTX group) or immediately prior to recording (acute CTX group). Thus, all sampled PbN neurons received indirect input from taste nerves other than the CT. Compared to acute CTX rats, chronic CTX animals had significantly higher responses to stimulation with 0.1 and 0.5 M NH4Cl, 0.1 NaCl, and 0.01 M citric acid. Activity to 0.5 M sucrose and 0.01 M quinine stimulation was not significantly different between groups. Neurons from chronic CTX animals also had larger interstimulus correlations and significantly higher entropy, suggesting that neurons in this group were more likely to be activated by stimulation with multiple tastants. Although neural responses were higher in the PbN of chronic CTX rats compared to acute-sectioned controls, taste-evoked activity was much lower than observed in previous reports, suggesting permanent deficits in taste signaling. These findings demonstrate that the developing gustatory hindbrain exhibits high functional plasticity following early nerve injury.

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Temporal signatures of criticality in human cortical excitability as probed by early somatosensory responses

10.1101/809285 ◽

2019 ◽

Author(s):

T. Stephani ◽

G. Waterstraat ◽

S. Haufe ◽

G. Curio ◽

A. Villringer ◽

...

Keyword(s):

Neural Networks ◽

Neural Activity ◽

Critical State ◽

Cortical Excitability ◽

Temporal Organization ◽

Neural Responses ◽

Scale Free ◽

Spatio Temporal ◽

Evoked Activity ◽

The Impact

AbstractBrain responses vary considerably from moment to moment, even to identical sensory stimuli. This has been attributed to changes in instantaneous neuronal states determining the system’s excitability. Yet the spatio-temporal organization of these dynamics remains poorly understood. Here we test whether variability in stimulus-evoked activity can be interpreted within the framework of criticality, which postulates dynamics of neural systems to be tuned towards the phase transition between stability and instability as is reflected in scale-free fluctuations in spontaneous neural activity. Using a novel non-invasive approach in 33 male participants, we tracked instantaneous cortical excitability by inferring the magnitude of excitatory post-synaptic currents from the N20 component of the somatosensory evoked potential. Fluctuations of cortical excitability demonstrated long-range temporal dependencies decaying according to a power law across trials – a hallmark of systems at critical states. As these dynamics covaried with changes in pre-stimulus oscillatory activity in the alpha band (8–13 Hz), we establish a mechanistic link between ongoing and evoked activity through cortical excitability and argue that the co-emergence of common temporal power laws may indeed originate from neural networks poised close to a critical state. In contrast, no signatures of criticality were found in subcortical or peripheral nerve activity. Thus, criticality may represent a parsimonious organizing principle of variability in stimulus-related brain processes on a cortical level, possibly reflecting a delicate equilibrium between robustness and flexibility of neural responses to external stimuli.Significance StatementVariability of neural responses in primary sensory areas is puzzling, as it is detrimental to the exact mapping between stimulus features and neural activity. However, such variability can be beneficial for information processing in neural networks if it is of a specific nature, namely if dynamics are poised at a so-called critical state characterized by a scale-free spatio-temporal structure. Here, we demonstrate the existence of a link between signatures of criticality in ongoing and evoked activity through cortical excitability, which fills the long-standing gap between two major directions of research on neural variability: The impact of instantaneous brain states on stimulus processing on the one hand and the scale-free organization of spatio-temporal network dynamics of spontaneous activity on the other.

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Combining CRISPR/Cas9 and brain imaging: from genes to molecules to networks

10.1101/2021.09.10.459766 ◽

2021 ◽

Author(s):

Sabina Marciano ◽

Tudor Mihai Ionescu ◽

Ran Sing Saw ◽

Rachel Y. Cheong ◽

Deniz Kirik ◽

...

Keyword(s):

Ion Channels ◽

Molecular Imaging ◽

Gene Networks ◽

Gene Editing ◽

Neuronal Cell ◽

Substantia Nigra Pars Compacta ◽

Adult Rats ◽

Brain Connectome ◽

The Impact

AbstractReceptors, transporters and ion channels are important targets for therapy development in neurological diseases including Alzheimeŕs disease, Parkinsońs disease, epilepsy, schizophrenia and major depression. Several receptors and ion channels identified by next generation sequencing may be involved in disease initiation and progression but their mechanistic role in pathogenesis is often poorly understood. Gene editing and in vivo imaging approaches will help to identify the molecular and functional role of these targets and the consequence of their regional dysfunction on whole brain level. Here, we combine CRISPR/Cas9 gene-editing with in vivo positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to investigate the direct link between genes, molecules, and the brain connectome. The extensive knowledge of the Slc18a2 gene encoding the vesicular monoamine transporter (VMAT2), involved in the storage and release of dopamine, makes it an excellent target for studying the gene networks relationships while structurally preserving neuronal integrity and function. We edited the Slc18a2 in the substantia nigra pars compacta of adult rats and used in vivo molecular imaging besides behavioral, histological, and biochemical assessments to characterize the CRISPR/Cas9-mediated VMAT2 knockdown. Simultaneous PET/fMRI was performed to investigate molecular and functional brain alterations. We found that stage-specific adaptations of brain functional connectivity follow the selective impairment of presynaptic dopamine storage and release. Our study reveals that recruiting different brain networks is an early response to the dopaminergic dysfunction preceding neuronal cell loss. Our combinatorial approach is a novel tool to investigate the impact of specific genes on brain molecular and functional dynamics which will help to develop tailored therapies for normalizing brain function. The method can easily be transferred to higher-order species allowing for a direct comparison of the molecular imaging findings.

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Selective role of neuropeptide Y receptor subtype Y2 in the control of gonadotropin secretion in the rat

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00274.2007 ◽

2007 ◽

Vol 293 (5) ◽

pp. E1385-E1392 ◽

Cited By ~ 16

Author(s):

L. Pinilla ◽

R. Fernández-Fernández ◽

J. Roa ◽

J. M. Castellano ◽

M. Tena-Sempere ◽

...

Keyword(s):

Neuropeptide Y ◽

Male Rats ◽

Receptor Subtype ◽

Central Administration ◽

Adult Rats ◽

Gonadotropin Secretion ◽

Gonadotropic Axis ◽

The Impact

Different signals with key roles in energy homeostasis regulate the reproductive axis. These include neuropeptide Y and polypeptide YY3-36, whose type Y2 receptor is the most abundant of this family in the brain. We evaluated herein the putative roles of Y2 receptors in the control of gonadotropin secretion by means of central administration of PYY13-36 (agonist of Y2 receptors) and BIIE 0246 (antagonist of Y2 receptors) to intact and orchidectomized male rats. In addition, the ability of PYY13-36 to elicit GnRH and gonadotropin secretion in vitro and the impact of fasting on LH responses to PYY13-36 in vivo were also monitored. Central administration of PYY13-36 significantly decreased the circulating levels of both gonadotropins, an effect that was observed in prepubertal and adult rats. Yet a dual action of Y2 receptors in the control of male gonadotropic axis was evidenced as their activation induced 1) stimulation of gonadotropin responses to GnRH at the pituitary but 2) inhibition of GnRH secretion at the hypothalamus. Antagonization of Y2 receptors failed to modify basal LH secretion in intact males either after being fed ad libitum or after being fasted. In contrast, their central blockade in orchidectomized rats evoked a significant increase in circulating LH and FSH level, suggesting the constitutive activation of Y2 receptor in such stimulated conditions. In summary, our data evidence a complex mode of action of Y2 receptors in the control of gonadotropic axis, with stimulatory and inhibitory actions at different levels of the system that are sensitive to the gonadal status.

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Aberrant Patterns of Sensory-Evoked Activity in the Olfactory Bulb of LRRK2 Knockout Mice

Cells ◽

10.3390/cells10113212 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3212

Author(s):

Andrea Maset ◽

Marco Albanesi ◽

Antonio di Soccio ◽

Martina Canova ◽

Marco dal Maschio ◽

...

Keyword(s):

Olfactory Bulb ◽

Intracellular Signaling ◽

System Level ◽

Strong Impact ◽

Lrrk2 Gene ◽

Evoked Activity ◽

Sensory Evoked ◽

The Impact

The LRRK2 gene is the major genetic determinant of familiar Parkinson’s disease (PD). Leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein involved in several intracellular signaling pathways. A wealth of evidence indicates that LRRK2 is enriched at the presynaptic compartment where it regulates vesicle trafficking and neurotransmitter release. However, whether the role of LRRK2 affects neuronal networks dynamic at systems level remains unknown. Addressing this question is critical to unravel the impact of LRRK2 on brain function. Here, combining behavioral tests, electrophysiological recordings, and functional imaging, we investigated neuronal network dynamics, in vivo, in the olfactory bulb of mice carrying a null mutation in LRRK2 gene (LRRK2 knockout, LRRK2 KO, mice). We found that LRRK2 KO mice exhibit olfactory behavioral deficits. At the circuit level, the lack of LRRK2 expression results in altered gamma rhythms and odorant-evoked activity with significant impairments, while the spontaneous activity exhibited limited alterations. Overall, our data in the olfactory bulb suggest that the multifaced role of LRRK2 has a strong impact at system level when the network is engaged in active sensory processing.

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MK-801-induced behavioral and dopaminergic responses in the shell part of the nucleus accumbens in adult rats are disrupted after neonatal blockade of the ventral subiculum

10.1101/2021.02.16.431488 ◽

2021 ◽

Author(s):

Hana Saoud ◽

Elora Kereselidze ◽

Séverine Eybrard ◽

Alain Louilot

Keyword(s):

Locomotor Activity ◽

Nucleus Accumbens ◽

Nmda Receptors ◽

Adult Rats ◽

Mk 801 ◽

Animal Modeling ◽

Ventral Subiculum ◽

Related Proteins ◽

The Impact

AbstractThe present study was conducted in the context of animal modeling of schizophrenia. It investigated in adult rats, after transient neonatal blockade of the ventral subiculum (VSub), the impact of a very specific non-competitive antagonist of NMDA receptors (MK-801) on locomotor activity and dopaminergic (DAergic) responses in the dorsomedial shell part of the nucleus accumbens (Nacc), a striatal subregion described as the common target region for antipsychotics.The functional neonatal inactivation of the VSub was achieved by local microinjection of tetrodotoxin (TTX) at postnatal day 8 (PND8). Control pups were microinjected with the solvent phosphate buffered saline (PBS). Locomotor responses and DAergic variations in the dorsomedial shell part of the Nacc were measured simultaneously using in vivo voltammetry in awake, freely moving animals after sc administration of MK-801. The following results were obtained: 1) a dose-dependent increase in locomotor activity in PBS and TTX animals, greater in TTX rats/PBS rats; and 2) divergent DAergic responses for PBS and TTX animals. A decrease in DA levels with a return to around basal values was observed in PBS animals. An increase in DA levels was obtained in TTX animals. The present data suggest that neonatal blockade of the VSub results in disruption in NMDA glutamatergic transmission, causing a disturbance in DA release in the dorsomedial shell in adults rats. In the context of animal modeling of schizophrenia using the same approach it would be interesting to investigate possible changes in postsynaptic NMDA receptors-related proteins in the dorsomedial shell region in the Nacc.

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Supplemental Material for Behavioral and Neural Responses to Infant and Adult Tears: The Impact of Maternal Love Withdrawal

Emotion ◽

10.1037/emo0000288.supp ◽

2017 ◽

Keyword(s):

Neural Responses ◽

Maternal Love ◽

The Impact

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Experimental Study of the Impact of Alisma plantago-aquatica Secretions on Pathogenic Bacteria

Agricultural science and practice ◽

10.15407/agrisp1.03.003 ◽

2014 ◽

Vol 1 (3) ◽

pp. 3-7

Author(s):

O. Zhukorskyy ◽

O. Hulay

Keyword(s):

Pathogenic Bacteria ◽

Initial Density ◽

Biologically Active ◽

Erysipelothrix Rhusiopathiae ◽

Natural Focus ◽

Test Species ◽

Popula Tions ◽

And Control ◽

The Impact

Aim. To estimate the impact of in vivo secretions of water plantain (Alisma plantago-aquatica) on the popula- tions of pathogenic bacteria Erysipelothrix rhusiopathiae. Methods. The plants were isolated from their natural conditions, the roots were washed from the substrate residues and cultivated in laboratory conditions for 10 days to heal the damage. Then the water was changed; seven days later the selected samples were sterilized using fi lters with 0.2 μm pore diameter. The dilution of water plantain root diffusates in the experimental samples was 1:10–1:10,000. The initial density of E. rhusiopathiae bacteria populations was the same for both experimental and control samples. The estimation of the results was conducted 48 hours later. Results. When the dilution of root diffusates was 1:10, the density of erysipelothrixes in the experimental samples was 11.26 times higher than that of the control, on average, the dilution of 1:100 − 6.16 times higher, 1:1000 – 3.22 times higher, 1:10,000 – 1.81 times higher, respectively. Conclusions. The plants of A. plantago-aquatica species are capable of affecting the populations of E. rhusiopathiae pathogenic bacteria via the secretion of biologically active substances into the environment. The consequences of this interaction are positive for the abovementioned bacteria, which is demon- strated by the increase in the density of their populations in the experiment compared to the control. The intensity of the stimulating effect on the populations of E. rhusiopathiae in the root diffusates of A. plantago-aquatica is re- ciprocally dependent on the degree of their dilution. The investigated impact of water plantain on erysipelothrixes should be related to the topical type of biocenotic connections, the formation of which between the test species in the ecosystems might promote maintaining the potential of natural focus of rabies. Keywords: Alisma plantago-aquatica, in vivo secretions, Erysipelothrix rhusiopathiae, population density, topical type of connections.

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Curcumin-containing Silver Nanoparticles prevent carbon tetrachlorideinduced hepatotoxicity in mice

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666201211100830 ◽

2020 ◽

Vol 23 ◽

Author(s):

Hossam Ebaid ◽

Mohamed Habila ◽

Iftekhar Hassan ◽

Jameel Al-Tamimi ◽

Mohamed S. Omar ◽

...

Keyword(s):

Dna Damage ◽

Silver Nanoparticles ◽

Nuclear Dna ◽

Liquid Paraffin ◽

Tail Length ◽

Hepatic Tissue ◽

Tissue Destruction ◽

Group 2 ◽

The Impact

Background: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Results: Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPs-curcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Conclusion: Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo. This agent has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.

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The Impact of L-Carnitine and Coenzyme Q10 as Protection Against Busulfan-Oxidative Stress in the Liver of Adult Rats

The Natural Products Journal ◽

10.2174/2210315509666190723131511 ◽

2020 ◽

Vol 10 (5) ◽

pp. 578-586

Author(s):

Areeg M. Abdelrazek ◽

Shimaa A. Haredy

Keyword(s):

Oxidative Stress ◽

Coenzyme Q10 ◽

Protective Role ◽

Albino Rats ◽

Distilled Water ◽

Negative Effects ◽

Adult Rats ◽

Stress Damage ◽

The Impact ◽

Liver Tissues

Background: Busulfan (Bu) is an anticancer drug with a variety of adverse effects for cancer patients. Oxidative stress has been considered as a common pathological mechanism and it has a key role in the initiation and progression of liver injury by Bu. Aim: The study aimed to evaluate the antioxidant impact of L-Carnitine and Coenzyme Q10 and their protective role against oxidative stress damage in liver tissues. Methods and Material: Thirty-six albino rats were divided equally into six groups. G1 (con), received I.P. injection of DMSO plus 1 ml of distilled water daily by oral gavages; G2 (Bu), received I.P. injection of Bu plus 1 ml of the distilled water daily; G3 (L-Car), received 1 ml of L-Car orally; G4 (Bu + L-Car) received I.P. injection of Bu plus 1 ml of L-Car, G5 (CoQ10) 1 ml of CoQ10 daily; and G6 (Bu + CoQ10) received I.P. injection of Bu plus 1 ml of CoQ10 daily. Results: The recent data showed that Bu induced significant (P<0.05) elevation in serum ALT, AST, liver GSSG, NO, MDA and 8-OHDG, while showing significant (P<0.05) decrease in liver GSH and ATP. On the other hand, L-Carnitine and Coenzyme Q10 ameliorated the negative effects prompted by Bu. Immunohistochemical expression of caspase-3 in liver tissues reported pathological alterations in Bu group while also showed significant recovery in L-Car more than CoQ10. Conclusion: L-Car, as well as CoQ10, can enhance the hepatotoxic effects of Bu by promoting energy production in oxidative phosphorylation process and by scavenging the free radicals.

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