Neuronal excitability and sensory responsiveness in the thalamo‐cortical network in a novel rat model of isoelectric brain state

The gastrointestinal system may be involved in the etiopathogenesis of the insulin-resistant brain state (IRBS) and Alzheimer’s disease (AD). Gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is being explored as a potential therapy as activation of brain GLP-1 receptors (GLP-1R) exerts neuroprotection and controls peripheral metabolism. Intracerebroventricular administration of streptozotocin (STZ-icv) is used to model IRBS and GLP-1 dyshomeostasis seems to be involved in the development of neuropathological changes. The aim was to explore (i) gastrointestinal homeostasis in the STZ-icv model (ii) assess whether the brain GLP-1 is involved in the regulation of gastrointestinal redox homeostasis and (iii) analyze whether brain-gut GLP-1 axis is functional in the STZ-icv animals. Acute intracerebroventricular treatment with exendin-3(9-39)amide was used for pharmacological inhibition of brain GLP-1R in the control and STZ-icv rats, and oxidative stress was assessed in plasma, duodenum and ileum. Acute inhibition of brain GLP-1R increased plasma oxidative stress. TBARS were increased, and low molecular weight thiols (LMWT), protein sulfhydryls (SH), and superoxide dismutase (SOD) were decreased in the duodenum, but not in the ileum of the controls. In the STZ-icv, TBARS and CAT were increased, LMWT and SH were decreased at baseline, and no further increment of oxidative stress was observed upon central GLP-1R inhibition. The presented results indicate that (i) oxidative stress is increased in the duodenum of the STZ-icv rat model of AD, (ii) brain GLP-1R signaling is involved in systemic redox regulation, (iii) brain-gut GLP-1 axis regulates duodenal, but not ileal redox homeostasis, and iv) brain-gut GLP-1 axis is dysfunctional in the STZ-icv model.

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Induction of an Isoelectric Brain State to Investigate the Impact of Endogenous Synaptic Activity on Neuronal Excitability In Vivo

Journal of Visualized Experiments ◽

10.3791/53576 ◽

2016 ◽

Author(s):

Tristan Altwegg-Boussac ◽

Séverine Mahon ◽

Mario Chavez ◽

Stéphane Charpier ◽

Adrien E. Schramm

Keyword(s):

Neuronal Excitability ◽

Synaptic Activity ◽

Brain State ◽

The Impact

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All-optical electrophysiology reveals brain-state dependent changes in hippocampal subthreshold dynamics and excitability

10.1101/281618 ◽

2018 ◽

Cited By ~ 16

Author(s):

Yoav Adam ◽

Jeong J. Kim ◽

Shan Lou ◽

Yongxin Zhao ◽

Daan Brinks ◽

...

Keyword(s):

High Speed ◽

Near Infrared ◽

Neuronal Excitability ◽

Signal To Noise Ratio ◽

Brain State ◽

Promising Tool ◽

State Dependent ◽

Subthreshold Voltage ◽

Targeted Gene Expression

AbstractA technology to record membrane potential from multiple neurons, simultaneously, in behaving animals will have a transformative impact on neuroscience research1. Parallel recordings could reveal the subthreshold potentials and intercellular correlations that underlie network behavior2. Paired stimulation and recording can further reveal the input-output properties of individual cells or networks in the context of different brain states3. Genetically encoded voltage indicators are a promising tool for these purposes, but were so far limited to single-cell recordings with marginal signal to noise ratio (SNR) in vivo4-6. We developed improved near infrared voltage indicators, high speed microscopes and targeted gene expression schemes which enabled recordings of supra- and subthreshold voltage dynamics from multiple neurons simultaneously in mouse hippocampus, in vivo. The reporters revealed sub-cellular details of back-propagating action potentials, correlations in sub-threshold voltage between multiple cells, and changes in dynamics associated with transitions from resting to locomotion. In combination with optogenetic stimulation, the reporters revealed brain state-dependent changes in neuronal excitability, reflecting the interplay of excitatory and inhibitory synaptic inputs. These tools open the possibility for detailed explorations of network dynamics in the context of behavior.

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Disbalance of the intestinal epithelial cell turnover and apoptosis in a rat model of sporadic Alzheimer’s disease

10.1101/2021.04.22.440947 ◽

2021 ◽

Author(s):

Jan Homolak ◽

Ana Babic Perhoc ◽

Ana Knezovic ◽

Jelena Osmanovic Barilar ◽

Fatma Koc ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cell ◽

Rat Model ◽

Redox Regulation ◽

Caspase 3 ◽

Morphological Changes ◽

Brain State ◽

Cell Turnover ◽

Functional Changes ◽

The Brain

AbstractBackgroundDyshomeostasis of the gastrointestinal (GI) system is investigated as a potential contributor to metabolic dysfunction, systemic and neuro-inflammation recognized as important pathophysiological drivers of neurodegeneration. Gastrointestinal redox dyshomeostasis and dysfunctional brain-gut incretin axis have been reported in the rat model of insulin-resistant brain state (IRBS)-driven neurodegeneration induced by intracerebroventricular administration of streptozotocin (STZ-icv). The aim was to assess i) whether GI oxidative stress is accompanied by structural and functional changes of the epithelial barrier; ii) whether the brain glucose-dependent insulinotropic polypeptide receptor (GIP-R) is also involved in redox regulation of the gut; and iii) whether the STZ-icv brain-gut axis is resistant to pharmacological inhibition of the brain GIP-R.MethodsForty three-month-old male Wistar rats were treated with 3mg/kg STZ-icv or vehicle. One month later the animals were randomized to receive either saline or 85 μg/kg GIP-R inhibitor [Pro3]-GIP intracerebroventricularly and sacrificed 30 minutes later. Thiobarbituric acid reactive substances (TBARS) were measured in plasma and duodenum. Duodenal sections were subjected to morphometric analysis. Caspase-3 expression and activation were analyzed by western blot and spatial signal analysis was done by multiplex fluorescent signal amplification (MFSA). Data were analyzed by linear and linear mixed modeling, and exploration was done by principal component analysis.ResultsInhibition of the brain GIP-R decreased plasma TBARS in the controls and the STZ-icv animals and increased duodenal TBARS only in the controls. Acute inhibition of brain GIP-R affects duodenal epithelial cell, but not villus structure, while all morphometric parameters were altered in the STZ-icv-treated animals. Morphometric changes in the STZ-icv animals were accompanied by reduced levels of activated and total regulator of apoptosis – caspase-3. Acute inhibition of brain GIP-R inactivated duodenal apoptosis at the level of caspase-3 activation.ConclusionsBrain GIP-R is involved in the regulation of the systemic and duodenal redox homeostasis and epithelial function. Duodenal oxidative stress in the STZ-icv rats is accompanied by the resistance of the brain-gut GIP axis and morphological changes indicative of abnormal epithelial cell turnover and dysfunctional GI barrier. Dysfunction of the brain-gut incretin axis might be an important etiopathogenetic factor in neurodegeneration and a potential pharmacological target.

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Quantifying epileptogenesis in rats with spontaneous and responsive brain state dynamics

Brain Communications ◽

10.1093/braincomms/fcaa048 ◽

2020 ◽

Vol 2 (1) ◽

Cited By ~ 3

Author(s):

Dakota N Crisp ◽

Warwick Cheung ◽

Stephen V Gliske ◽

Alan Lai ◽

Dean R Freestone ◽

...

Keyword(s):

Electrical Stimulation ◽

Rat Model ◽

Tetanus Toxin ◽

Brain State ◽

Induced Responses ◽

Spontaneous Seizure ◽

Seizure Onset ◽

Theoretical Predictions ◽

Over Time

Abstract There is a crucial need to identify biomarkers of epileptogenesis that will help predict later development of seizures. This work identifies two novel electrophysiological biomarkers that quantify epilepsy progression in a rat model of epileptogenesis. The long-term tetanus toxin rat model was used to show the development and remission of epilepsy over several weeks. We measured the response to periodic electrical stimulation and features of spontaneous seizure dynamics over several weeks. Both biomarkers showed dramatic changes during epileptogenesis. Electrically induced responses began to change several days before seizures began and continued to change until seizures resolved. These changes were consistent across animals and allowed development of an algorithm that could differentiate which animals would later develop epilepsy. Once seizures began, there was a progression of seizure dynamics that closely follows recent theoretical predictions, suggesting that the underlying brain state was changing over time. This research demonstrates that induced electrical responses and seizure onset dynamics are useful biomarkers to quantify dynamical changes in epileptogenesis. These tools hold promise for robust quantification of the underlying epileptogenicity and prediction of later development of seizures.

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Controlling Brain State Prior to Stimulation of Parietal Cortex Prevents Deterioration of Sustained Attention

Cerebral Cortex Communications ◽

10.1093/texcom/tgaa069 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Grace Edwards ◽

Federica Contò ◽

Loryn K Bucci ◽

Lorella Battelli

Keyword(s):

Sustained Attention ◽

Neuronal Excitability ◽

Right Hemisphere ◽

Repetitive Transcranial Magnetic Stimulation ◽

Random Noise ◽

Impact Behavior ◽

Brain State ◽

Functional Compensation ◽

Transcranial Random Noise Stimulation ◽

The Impact

Abstract Sustained attention is a limited resource which declines during daily tasks. Such decay is exacerbated in clinical and aging populations. Inhibition of the intraparietal sulcus (IPS), using low-frequency repetitive transcranial magnetic stimulation (LF-rTMS), can lead to an upregulation of functional communication within the attention network. Attributed to functional compensation for the inhibited node, this boost lasts for tens of minutes poststimulation. Despite the neural change, no behavioral correlate has been found in healthy subjects, a necessary direct evidence of functional compensation. To understand the functional significance of neuromodulatory induced fluctuations on attention, we sought to boost the impact of LF-rTMS to impact behavior. We controlled brain state prior to LF-rTMS using high-frequency transcranial random noise stimulation (HF-tRNS), shown to increase and stabilize neuronal excitability. Using fMRI-guided stimulation protocols combining HF-tRNS and LF-rTMS, we tested the poststimulation impact on sustained attention with multiple object tracking (MOT). While attention deteriorated across time in control conditions, HF-tRNS followed by LF-rTMS doubled sustained attention capacity to 94 min. Multimethod stimulation was more effective when targeting right IPS, supporting specialized attention processing in the right hemisphere. Used in cognitive domains dependent on network-wide neural activity, this tool may cause lasting neural compensation useful for clinical rehabilitation.

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Dehydrocrenatidine Inhibits Voltage-Gated Sodium Channels and Ameliorates Mechanic Allodia in a Rat Model of Neuropathic Pain

Toxins ◽

10.3390/toxins11040229 ◽

2019 ◽

Vol 11 (4) ◽

pp. 229 ◽

Cited By ~ 4

Author(s):

Fang Zhao ◽

Qinglian Tang ◽

Jian Xu ◽

Shuangyan Wang ◽

Shaoheng Li ◽

...

Keyword(s):

Neuropathic Pain ◽

Rat Model ◽

Analgesic Effect ◽

Neuronal Excitability ◽

Active Components ◽

Action Potential Firing ◽

Voltage Gated ◽

Voltage Gated Sodium Channels ◽

Ic50 Values ◽

Medical Plant

Picrasma quassioides (D. Don) Benn, a medical plant, is used in clinic to treat inflammation, pain, sore throat, and eczema. The alkaloids are the main active components in P. quassioides. In this study, we examined the analgesic effect of dehydrocrenatidine (DHCT), a β-carboline alkaloid abundantly found in P. quassioides in a neuropathic pain rat model of a sciatic nerve chronic constriction injury. DHCT dose-dependently attenuated the mechanic allodynia. In acutely isolated dorsal root ganglion, DHCT completely suppressed the action potential firing. Further electrophysiological characterization demonstrated that DHCT suppressed both tetrodotoxin-resistant (TTX-R) and sensitive (TTX-S) voltage-gated sodium channel (VGSC) currents with IC50 values of 12.36 μM and 4.87 µM, respectively. DHCT shifted half-maximal voltage (V1/2) of inactivation to hyperpolarizing direction by ~16.7 mV in TTX-S VGSCs. In TTX-R VGSCs, DHCT shifted V1/2 of inactivation voltage to hyperpolarizing direction and V1/2 of activation voltage to more depolarizing potential by ~23.9 mV and ~12.2 mV, respectively. DHCT preferred to interact with an inactivated state of VGSCs and prolonged the repriming time in both TTX-S and TTX-R VGSCs, transiting the channels into a slow inactivated state from a fast inactivated state. Considered together, these data demonstrated that the analgesic effect of DHCT was likely though the inhibition of neuronal excitability.

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Effect of Neuronal Excitability in Hippocampal CA1 Area on Auditory Pathway in a Rat Model of Tinnitus

Chinese Medical Journal ◽

10.4103/0366-6999.238148 ◽

2018 ◽

Vol 131 (16) ◽

pp. 1969-1974

Author(s):

Yu-Jing Ding ◽

Yu Song ◽

Jun-Xiu Liu ◽

Ya-Li Du ◽

Li Zhu ◽

...

Keyword(s):

Rat Model ◽

Neuronal Excitability ◽

Auditory Pathway ◽

Hippocampal Ca1 ◽

Hippocampal Ca1 Area ◽

Ca1 Area

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Enhancement of intrinsic neuronal excitability‐mediated by a reduction in hyperpolarization‐activated cation current (I h ) in hippocampal CA1 neurons in a rat model of traumatic brain injury

Hippocampus ◽

10.1002/hipo.23270 ◽

2020 ◽

Author(s):

Seyed Asaad Karimi ◽

Narges Hosseinmardi ◽

Mohammad Sayyah ◽

Razieh Hajisoltani ◽

Mahyar Janahmadi

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Rat Model ◽

Neuronal Excitability ◽

Ca1 Neurons ◽

Cation Current ◽

Hippocampal Ca1 Neurons ◽

Hippocampal Ca1

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Retrosplenial Cortex Contributes to Network Changes during Seizures in the GAERS Absence Epilepsy Rat Model

Cerebral Cortex Communications ◽

10.1093/texcom/tgab023 ◽

2021 ◽

Author(s):

Lydia Wachsmuth ◽

Maia Datunashvili ◽

Katharina Kemper ◽

Franziska Albers ◽

Henriette Lambers ◽

...

Keyword(s):

Neuronal Excitability ◽

Pyramidal Neurons ◽

Local Level ◽

Small World ◽

Resting State Fmri ◽

Absence Epilepsy ◽

Retrosplenial Cortex ◽

Synaptic Activity ◽

Brain State ◽

Cortical Regions

Abstract Resting state-fMRI (rs-fMRI) was performed to explore brain networks in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and in non-epileptic controls (NEC) during monitoring of the brain state by simultaneous optical Ca2+-recordings. Graph theoretical analysis allowed for identification of acute and chronic network changes and revealed preserved small world topology before and after seizure onset. The most prominent acute change in network organization during seizures was the segregation of cortical regions from the remaining brain. Stronger connections between thalamic with limbic regions compared to pre-seizure state indicated network regularization during seizures. When comparing between strains, intra-thalamic connections were prominent in NEC, on local level represented by higher thalamic strengths and hub scores. Subtle differences were observed for retrosplenial cortex (RS), forming more connections beyond cortex in epileptic rats, and showing a tendency to lateralization during seizures. A potential role of RS as hub between subcortical and cortical regions in epilepsy was supported by increased numbers of parvalbumin-positive (PV+) interneurons together with enhanced inhibitory synaptic activity and neuronal excitability in pyramidal neurons. By combining multimodal fMRI data, graph theoretical methods, and electrophysiological recordings we identified the RS as promising target for modulation of seizure activity and/or comorbidities.

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