scholarly journals Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1)-mediated plasticity in the paraventricular thalamic nucleus promotes a fundamental adaptation to stress

2021 ◽  
Author(s):  
Brian F Corbett ◽  
Sandra Luz ◽  
Jay Arner ◽  
Abigail Vigderman ◽  
Kimberly Urban ◽  
...  
Keyword(s):  
Neural Activity ◽  
Molecular Mechanisms ◽  
Thalamic Nucleus ◽  
Field Potential ◽  
Brain Regions ◽  
Repeated Exposure ◽  
Designer Drugs ◽  
Sprague Dawley ◽  
Post Traumatic Stress ◽  
Neural Connections

BACKGROUND: Habituation is defined as a progressive decline in response to repeated exposure to a familiar and predictable stimulus and is highly conserved across species. Disrupted habituation is a signature of post-traumatic stress disorder (PTSD). In rodents, habituation is observed in neural, neuroendocrine and behavioral responses to repeated exposure to the predictable and moderately intense stress or restraint. We previously demonstrated that lesions to the posterior division of the paraventricular thalamic nucleus (pPVT) impairs habituation. However, the underlying molecular mechanisms and specific neural connections among the pPVT and other brain regions that underlie habituation are unknown. METHODS: Behavioral and neuroendocrine habituation was assessed in adult male Sprague-Dawley restraints using the repeated restraint paradigm. Pan neuronal and Cre-dependent Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were used to chemogenetically inhibit the pPVT and the subpopulation of pPVT neurons that project to the medial prefrontal cortex (mPFC), respectively. Activity-regulated cytoskeleton-associated protein (Arc) expression was knocked down in the pPVT using siRNA directed towards Arc. Golgi staining was used to assess structural plasticity of pPVT neurons. Local field potential recordings were used to assess coherent neural activity between the pPVT and mPFC. The attentional set-shifting task was used to assess mPFC-dependent behavior. RESULTS: Here, we show that Arc promotes habituation by increasing stress-induced spinogenesis in the pPVT, increasing coherent neural activity with the mPFC, and improving mPFC-mediated cognitive flexibility. CONCLUSION: Our results demonstrate that Arc induction in the pPVT regulates habituation to repeated restraint and mPFC function.

scholarly journals miR-142 downregulation alleviates rat PTSD-like behaviors, reduces the level of inflammatory cytokine expression and apoptosis in hippocampus, and upregulates the expression of fragile X mental retardation protein

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Peng-Yin Nie ◽  
Lei Tong ◽  
Ming-Da Li ◽  
Chang-Hai Fu ◽  
Jun-Bo Peng ◽  
...  
Keyword(s):  
Fragile X ◽  
Brain Regions ◽  
Synaptic Proteins ◽  
Sprague Dawley ◽  
Post Traumatic Stress ◽  
Proinflammatory Mediators ◽  
Upstream Regulator ◽  
Trace Fear ◽  
Factor Α

Abstract Background FMRP is a selective mRNA-binding protein that regulates protein synthesis at synapses, and its loss may lead to the impairment of trace fear memory. Previously, we found that FMRP levels in the hippocampus of rats with post-traumatic stress disorder (PTSD) were decreased. However, the mechanism underlying these changes remains unclear. Methods Forty-eight male Sprague-Dawley rats were randomly divided into four groups. The experimental groups were treated with the single-prolonged stress (SPS) procedure and injected with a lentivirus-mediated inhibitor of miR-142-5p. Behavior test as well as morphology and molecular biology experiments were performed to detect the effect of miR-142 downregulation on PTSD, which was further verified by in vitro experiments. Results We found that silence of miRNA-142 (miR-142), an upstream regulator of FMRP, could alleviate PTSD-like behaviors of rats exposed to the SPS paradigm. MiR-142 silence not only decreased the levels of proinflammatory mediators, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, but also increased the expressive levels of synaptic proteins including PSD95 and synapsin I in the hippocampus, which was one of the key brain regions associated with PTSD. We further detected that miR-142 silence also downregulated the transportation of nuclear factor kappa-B (NF-κB) into the nuclei of neurons and might further affect the morphology of neurons. Conclusions The results revealed miR-142 downregulation could alleviate PTSD-like behaviors through attenuating neuroinflammation in the hippocampus of SPS rats by binding to FMRP.

scholarly journals Variable Response of Norepinephrine Transporter to Traumatic Stress and Relationship to Hyperarousal

2021 ◽  
Vol 15 ◽  
Author(s):  
Chiso Nwokafor ◽  
Lidia I. Serova ◽  
Arax Tanelian ◽  
Roxanna J. Nahvi ◽  
Esther L. Sabban
Keyword(s):  
Traumatic Stress ◽  
Neuropsychiatric Symptoms ◽  
Acoustic Startle ◽  
Norepinephrine Transporter ◽  
Brain Regions ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Post Traumatic Stress ◽  
Variable Response ◽  
Western Blots

The noradrenergic systems play a key role in stress triggered disorders such as post-traumatic stress disorder (PTSD). We hypothesized that traumatic stress will alter expression of norepinephrine transporter (NET) in locus coeruleus (LC) and its target brain regions which could be related to hyperarousal. Male Sprague-Dawley rats were subjected to single prolonged stress (SPS) and several weeks later the LC was isolated. NET mRNA levels in LC, determined by RT-PCR, displayed variable response with high and low responsive subgroups. In different cohort, acoustic startle response (ASR) was measured 2 weeks after SPS and levels of NET mRNA and protein in LC determined. The high NET responsive subgroup had greater hyperarousal. Nevertheless, NET protein levels, as determined by western blots, were lower than unstressed controls in LC, ventral hippocampus and medial prefrontal cortex and displayed considerable variability. Hypermethylation of specific CpG region in promoter of SLC6A2 gene, encoding NET, was present in the low, but not high, NET mRNA responsive subgroup. Taken together, the results demonstrate variability in stress elicited changes in NET gene expression and involvement of epigenetic changes. This may underlie mechanisms of susceptibility and resilience to traumatic stress triggered neuropsychiatric symptoms, especially hyperarousal.

scholarly journals Induced cortical oscillations in turtle cortex are coherent at the mesoscale of population activity, but not at the microscale of the membrane potential of neurons

2017 ◽  
Vol 118 (5) ◽  
pp. 2579-2591 ◽  
Author(s):  
Mahmood S. Hoseini ◽  
Jeff Pobst ◽  
Nathaniel Wright ◽  
Wesley Clawson ◽  
Woodrow Shew ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Membrane Potential ◽  
Neural Activity ◽  
Visual Stimulation ◽  
Field Potential ◽  
Brain Regions ◽  
Large Trial ◽  
Population Activity ◽  
Potential Oscillations ◽  
Time Frequency

Bursts of oscillatory neural activity have been hypothesized to be a core mechanism by which remote brain regions can communicate. Such a hypothesis raises the question to what extent oscillations are coherent across spatially distant neural populations. To address this question, we obtained local field potential (LFP) and membrane potential recordings from the visual cortex of turtle in response to visual stimulation of the retina. The time-frequency analysis of these recordings revealed pronounced bursts of oscillatory neural activity and a large trial-to-trial variability in the spectral and temporal properties of the observed oscillations. First, local bursts of oscillations varied from trial to trial in both burst duration and peak frequency. Second, oscillations of a given recording site were not autocoherent; i.e., the phase did not progress linearly in time. Third, LFP oscillations at spatially separate locations within the visual cortex were more phase coherent in the presence of visual stimulation than during ongoing activity. In contrast, the membrane potential oscillations from pairs of simultaneously recorded pyramidal neurons showed smaller phase coherence, which did not change when switching from black screen to visual stimulation. In conclusion, neuronal oscillations at distant locations in visual cortex are coherent at the mesoscale of population activity, but coherence is largely absent at the microscale of the membrane potential of neurons. NEW & NOTEWORTHY Coherent oscillatory neural activity has long been hypothesized as a potential mechanism for communication across locations in the brain. In this study we confirm the existence of coherent oscillations at the mesoscale of integrated cortical population activity. However, at the microscopic level of neurons, we find no evidence for coherence among oscillatory membrane potential fluctuations. These results raise questions about the applicability of the communication through coherence hypothesis to the level of the membrane potential.

scholarly journals The Relationship between BOLD and Neural Activity Arises from Temporally Sparse Events

2019 ◽  
Author(s):  
Xiaodi Zhang ◽  
Wen-Ju Pan ◽  
Shella Dawn Keilholz
Keyword(s):  
Neural Activity ◽  
Field Potential ◽  
High Amplitude ◽  
Brain Regions ◽  
Functional Networks ◽  
Time Varying ◽  
Bold Signal ◽  
Activation Patterns ◽  
Amplitude Data ◽  
Co Activation

Resting state functional magnetic resonance (rs-fMRI) imaging offers insights into how different brain regions are connected into functional networks. It was recently shown that networks that are almost identical to the ones created from conventional correlation analysis can be obtained from a subset of high-amplitude data, suggesting that the functional networks may be driven by instantaneous co-activations of multiple brain regions rather than ongoing oscillatory processes. The rs-fMRI studies, however, rely on the blood oxygen level dependent (BOLD) signal, which is only indirectly sensitive to neural activity through neurovascular coupling. To provide more direct evidence that the neuronal co-activation events produce the time-varying network patterns seen in rs-fMRI studies, we examined the simultaneous rs-fMRI and local field potential (LFP) recordings in rats performed in our lab over the past several years. We developed complementary analysis methods that focus on either the temporal or spatial domain, and found evidence that the interaction between LFP and BOLD may be driven by instantaneous co-activation events as well. BOLD maps triggered on high-amplitude LFP events resemble co-activation patterns created from rs-fMRI data alone, though the co-activation time points are defined differently in the two cases. Moreover, only LFP events that fall into the highest or lowest thirds of the amplitude distribution result in a BOLD signal that can be distinguished from noise. These findings provide evidence of an electrophysiological basis for the time-varying co-activation patterns observed in previous studies.

scholarly journals A Role for Gαz in regulating seizure susceptibility

2019 ◽  
Author(s):  
Rainbo Hultman ◽  
Okechi Boms ◽  
Stephen Mague ◽  
Dalton Hughes ◽  
Victor Nadler ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Seizure Activity ◽  
Dorsal Hippocampus ◽  
Field Potential ◽  
Brain Regions ◽  
Seizure Susceptibility ◽  
Electrographic Seizure ◽  
Pilocarpine Model ◽  
Local Field Potential Lfp

AbstractMuch about the molecular mechanisms underlying seizure susceptibility remains unknown. A number of studies have indicated that the neurotrophic factor BDNF plays an important role in mediating seizure susceptibility. Recently, we found that the heterotrimeric G – protein, Gz, which is known to endogenously couple to monoaminergic receptors, such as serotonin, norepinephrine and dopamine receptors, regulates BDNF-induced signaling and development in cortical neurons. Interestingly, several of the receptors that Gz endogenously couples to have also been shown to be associated with seizure phenotypes (5HT1A-serotonin and D2 dopamine). Here we characterized seizure susceptibility in Gz-null mice, behaviorally and electrographically, finding that Gz-null mice have increased seizure susceptibility using a modified version of the pilocarpine model of status epilepticus. Local field potential (LFP) data recorded from six brain regions-amygdala, dorsal hippocampus, ventral hippocampus, motor cortex, somatosensory cortex, and thalamus-showed robust electrographic seizure activity for Gz-null mice compared with low or no seizure activity in wild-type controls.

scholarly journals Large- and multi-scale networks in the rodent brain during novelty exploration

2020 ◽  
Author(s):  
Michael X Cohen ◽  
Bernhard Englitz ◽  
Arthur S C França
Keyword(s):  
Prefrontal Cortex ◽  
Parietal Cortex ◽  
Local Field ◽  
Neural Activity ◽  
Large Scale ◽  
Field Potential ◽  
Brain Regions ◽  
Data Availability ◽  
Data Matrix ◽  
Temporal Scales

AbstractNeural activity is coordinated across multiple spatial and temporal scales, and these patterns of coordination are implicated in both healthy and impaired cognitive operations. However, empirical cross-scale investigations are relatively infrequent, due to limited data availability and to the difficulty of analyzing rich multivariate datasets. Here we applied frequency-resolved multivariate source-separation analyses to characterize a large-scale dataset comprising spiking and local field potential activity recorded simultaneously in three brain regions (prefrontal cortex, parietal cortex, hippocampus) in freely-moving mice. We identified a constellation of multidimensional, inter-regional networks across a range of frequencies (2-200 Hz). These networks were reproducible within animals across different recording sessions, but varied across different animals, suggesting individual variability in network architecture. The theta band (~4-10 Hz) networks had several prominent features, including roughly equal contribution from all regions and strong inter-network synchronization. Overall, these findings demonstrate a multidimensional landscape of large-scale functional activations of cortical networks operating across multiple spatial, spectral, and temporal scales during open-field exploration.Significance statementNeural activity is synchronized over space, time, and frequency. To characterize the dynamics of large-scale networks spanning multiple brain regions, we recorded data from the prefrontal cortex, parietal cortex, and hippocampus in awake behaving mice, and pooled data from spiking activity and local field potentials into one data matrix. Frequency-specific multivariate decomposition methods revealed a cornucopia of neural networks defined by coherent spatiotemporal patterns over time. These findings reveal a rich, dynamic, and multivariate landscape of large-scale neural activity patterns during foraging behavior.

scholarly journals Fly seizure EEG: field potential activity in the Drosophila brain

2021 ◽  
Author(s):  
Atulya Iyengar ◽  
Chun-Fang Wu
Keyword(s):  
Neural Activity ◽  
Activity Patterns ◽  
Field Potential ◽  
Temporal Correlation ◽  
Brain Regions ◽  
High Frequency Stimulation ◽  
Straightforward Method ◽  
Drosophila Brain ◽  
Frequency Stimulation ◽  
Potential Activity

Hypersynchronous neural activity is a characteristic feature of seizures. Although many Drosophila mutants of epilepsy-related genes display clear behavioral spasms and motor unit hyperexcitability, field potential measurements of aberrant hypersynchronous activity across brain regions during seizures have yet to be described. Here, we report a straightforward method to observe local field potentials (LFPs) from the Drosophila brain to monitor ensemble neural activity during seizures in behaving tethered flies. High frequency stimulation across the brain reliably triggers a stereotypic sequence of electroconvulsive seizure (ECS) spike discharges readily detectable in the dorsal longitudinal muscle (DLM) and coupled with behavioral spasms. During seizure episodes, the LFP signal displayed characteristic large-amplitude oscillations with a stereotypic temporal correlation to DLM flight muscle spiking. ECS-related LFP events were clearly distinct from rest- and flight-associated LFP patterns. We further characterized the LFP activity during different types of seizures originating from genetic and pharmacological manipulations. In the 'bang-sensitive' sodium channel mutant bangsenseless (bss), the LFP pattern was prolonged, and the temporal correlation between LFP oscillations and DLM discharges was altered. Following administration of the pro-convulsant GABAA blocker picrotoxin, we uncovered a qualitatively different LFP activity pattern, which consisted of a slow (1-Hz), repetitive, waveform, closely coupled with DLM bursting and behavioral spasms. Our approach to record brain LFPs presents an initial framework for electrophysiological analysis of the complex brain-wide activity patterns in the large collection of Drosophila excitability mutants.

scholarly journals Exposure to 2.45 GHz Radiation Triggers Changes in HSP-70, Glucocorticoid Receptors and GFAP Biomarkers in Rat Brain

2021 ◽  
Vol 22 (10) ◽  
pp. 5103
Author(s):  
Haifa Othman ◽  
Alberto López-Furelos ◽  
José Manuel Leiro-Vidal ◽  
Mohamed Ammari ◽  
Mohsen Sakly ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Glucocorticoid Receptors ◽  
Brain Regions ◽  
Repeated Exposure ◽  
Limbic Cortex ◽  
Sprague Dawley ◽  
Hsp 70 ◽  
Tissue Heating ◽  
Radiation Regime ◽  
Set Up

Brain tissue may be especially sensitive to electromagnetic phenomena provoking signs of neural stress in cerebral activity. Fifty-four adult female Sprague-Dawley rats underwent ELISA and immunohistochemistry testing of four relevant anatomical areas of the cerebrum to measure biomarkers indicating induction of heat shock protein 70 (HSP-70), glucocorticoid receptors (GCR) or glial fibrillary acidic protein (GFAP) after single or repeated exposure to 2.45 GHz radiation in the experimental set-up. Neither radiation regime caused tissue heating, so thermal effects can be ruled out. A progressive decrease in GCR and HSP-70 was observed after acute or repeated irradiation in the somatosensory cortex, hypothalamus and hippocampus. In the limbic cortex; however, values for both biomarkers were significantly higher after repeated exposure to irradiation when compared to control animals. GFAP values in brain tissue after irradiation were not significantly different or were even lower than those of nonirradiated animals in all brain regions studied. Our results suggest that repeated exposure to 2.45 GHz elicited GCR/HSP-70 dysregulation in the brain, triggering a state of stress that could decrease tissue anti-inflammatory action without favoring glial proliferation and make the nervous system more vulnerable.

scholarly journals A Likelihood Method for Computing Selection Times in Spiking and Local Field Potential Activity

2010 ◽  
Vol 104 (6) ◽  
pp. 3705-3720 ◽  
Author(s):  
Arpan Banerjee ◽  
Heather L. Dean ◽  
Bijan Pesaran
Keyword(s):  
Local Field ◽  
Neural Activity ◽  
Local Field Potential ◽  
Posterior Parietal Cortex ◽  
Field Potential ◽  
Brain Regions ◽  
Likelihood Method ◽  
Neural Responses ◽  
Neural Processes ◽  
Alternative Hypotheses

The timing of neural responses to ongoing behavior is an important measure of the underlying neural processes. Neural processes are distributed across many different brain regions and measures of the timing of neural responses are routinely used to test relationships between different brain regions. Testing detailed models of functional neural circuitry underlying behavior depends on extracting information from single trials. Despite their importance, existing methods for analyzing the timing of information in neural signals on single trials remain limited in their scope and application. We develop a novel method for estimating the timing of information in neural activity that we use to measure selection times, when an observer can reliably use observations of neural activity to select between two descriptions of the activity. The method is designed to satisfy three criteria: selection times should be computed from single trials, they should be computed from both spiking and local field potential (LFP) activity, and they should allow us to make comparisons between different recordings. Our approach characterizes the timing of information in terms of an accumulated log-likelihood ratio (AccLLR), which distinguishes between two alternative hypotheses and uses the AccLLR to estimate the selection time. We develop the AccLLR procedure for binary discrimination using example recordings of spiking and LFP activity in the posterior parietal cortex of a monkey performing a memory-guided saccade task. We propose that the AccLLR method is a general and practical framework for the analysis of signal timing in the nervous system.

scholarly journals Dynamics of neural microstates in the VTA-striatal-prefrontal loop during novelty exploration in the rat

2020 ◽  
Author(s):  
A. Mishra ◽  
N. Marzban ◽  
M. X Cohen ◽  
B. Englitz
Keyword(s):  
Spatial Patterns ◽  
Neural Activity ◽  
Large Scale ◽  
Temporal Dynamics ◽  
Activity Patterns ◽  
Field Potential ◽  
Brain Regions ◽  
Brain Areas ◽  
Neural Recordings ◽  
Temporal Correlations

AbstractEEG microstates refer to quasi-stable spatial patterns of scalp potentials, and their dynamics have been linked to cognitive and behavioral states. Neural activity at single and multiunit levels also exhibit spatiotemporal coordination, but this spatial scale is difficult to relate to EEG. Here, we translated EEG microstate analysis to triple-area local field potential (LFP) recordings from up to 192 electrodes in rats to investigate the mesoscopic dynamics of neural microstates within and across brain regions.We performed simultaneous recordings from the prefrontal cortex (PFC), striatum (STR), and ventral tegmental area (VTA) during awake behavior (object novelty and exploration). We found that the LFP data can be accounted for by multiple, recurring, quasi-stable spatial activity patterns with an average period of stability of ~60-100 ms. The top four maps accounted for 60-80% of the total variance, compared to ~25% for shuffled data. Cross-correlation of the microstate time-series across brain regions revealed rhythmic patterns of microstate activations, which we interpret as a novel indicator of inter-regional, mesoscale synchronization. Furthermore, microstate features, and patterns of temporal correlations across microstates, were modulated by behavioural states such as movement and novel object exploration. These results support the existence of a functional mesoscopic organization across multiple brain areas, and open up the opportunity to investigate their relation to EEG microstates, of particular interest to the human research community.Significance StatementThe coordination of neural activity across the entire brain has remained elusive. Here we combine large-scale neural recordings at fine spatial resolution with the analysis of microstates, i.e. short-lived, recurring spatial patterns of neural activity. We demonstrate that the local activity in different brain areas can be accounted for by only a few microstates per region. These microstates exhibited temporal dynamics that were correlated across regions in rhythmic patterns. We demonstrate that these microstates are linked to behavior and exhibit different properties in the frequency domain during different behavioural states. In summary, LFP microstates provide an insightful approach to studying both mesoscopic and large-scale brain activation within and across regions.

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