Engagement of Rat Striatal Neurons by Cortical Epileptiform Activity Investigated With Paired Recordings

2004 ◽  
Vol 92 (5) ◽  
pp. 2725-2737 ◽  
Author(s):  
Enrico Bracci ◽  
Diego Centonze ◽  
Giorgio Bernardi ◽  
Paolo Calabresi
Keyword(s):  
Cortical Neurons ◽  
Epileptiform Activity ◽  
Brain Slices ◽  
Brain Structures ◽  
Extracellular Potassium ◽  
Striatal Neurons ◽  
Cholinergic Interneurons ◽  
Medial Agranular Cortex ◽  
The Impact ◽  
Oblique Slices

The striatum is thought to play an important role in the spreading of epilepsy from cortical areas to deeper brain structures, but this issue has not been addressed with intracellular techniques. Paired recordings were used to assess the impact of cortical epileptiform activity on striatal neurons in brain slices. Bath-application of 4-amynopyridine (100 μM) and bicuculline (20 μM) induced synchronized bursts in all pairs of cortical neurons (≤5 mm apart) in coronal, sagittal, and oblique slices (which preserve connections from the medial agranular cortex to the striatum). Under these conditions, striatal medium spiny neurons (MSs) displayed a strong increased spontaneous glutamatergic activity. This activity was not correlated to the cortical bursts and was asynchronous in pairs of MSs. Sporadic, large-amplitude synchronous depolarizations also occurred in MSs. These events were simultaneously detected in glial cells, suggesting that they were accompanied by considerable increases in extracellular potassium. In oblique slices, cortically driven bursts were also observed in MSs. These events were synchronized to cortical epileptiform bursts, depended on non– N-methyl-d-aspartate (NMDA) glutamate receptors, and persisted in the cortex, but not in the striatum, after disconnection of the two structures. During these bursts, MS membrane potential shifted to a depolarized value (59 ± 4 mV) on which an irregular waveform, occasionally eliciting spikes, was superimposed. Thus synchronous activation of a limited set of corticostriatal afferents can powerfully control MSs. Cholinergic interneurons located <120 μm from simultaneously recorded MSs, did not display cortically driven bursts, suggesting that these cells are much less easily engaged by cortical epileptiform activity.

Synaptic and Nonsynaptic Ictogenesis Occurs at Different Temperatures in Submerged and Interface Rat Brain Slices

2002 ◽  
Vol 87 (6) ◽  
pp. 2929-2935 ◽  
Author(s):  
S. Schuchmann ◽  
H. Meierkord ◽  
K. Stenkamp ◽  
J. Breustedt ◽  
O. Windmüller ◽  
...  
Keyword(s):  
Intracellular Ph ◽  
Extracellular Space ◽  
Room Temperature ◽  
Epileptiform Activity ◽  
Brain Slices ◽  
Extracellular Potassium ◽  
Interface Conditions ◽  
Epileptiform Discharges ◽  
Submerged Conditions ◽  
Space Volume

To investigate the temperature sensitivity of low-Ca2+-induced nonsynaptic and low-Mg2+-induced synaptic ictogenesis under submerged and interface conditions, we compared changes of extracellular field potential and extracellular potassium concentration at room temperature (23 ± 1°C; mean ± SD) and at 35 ± 1°C in hippocampal-entorhinal cortex slices. The induction of spontaneous epileptiform activity under interface conditions occurred at 35 ± 1°C in both models. In contrast, under submerged conditions, spontaneous epileptiform activity in low-Mg2+ artificial cerebrospinal fluid (ACSF) was observed at 35 ± 1°C, whereas epileptiform discharges induced by low-Ca2+ ACSF occurred only at room temperature. To investigate the different temperature effects under submerged and interface conditions, measurements of extra- and intracellular pH and extracellular space volume were performed. Lowering the temperature from 35 ± 1°C to room temperature effected a reduction in extracellular pH under submerged and interface conditions. Under submerged conditions, temperature changes had no significant influence on the intracellular pH in presence of either normal or low-Mg2+ ACSF. In contrast, application of low-Ca2+ ACSF effected a significant increase in intracellular pH at room temperature but not at 35 ± 1°C under submerged conditions. Therefore increasing intracellular pH by lowering the temperature in low-Ca2+ ACSF may push slices to spontaneous epileptiform activity by opening gap junctions. Finally, extracellular space volume significantly decreased by switching from submerged to interface conditions. The reduced extracellular space volume under interface conditions may lead to an enlarged ephaptic transmission and therefore promotes low-Mg2+- and low-Ca2+-induced spontaneous epileptiform activity. The results of the study indicate that gas-liquid interface and total-liquid submerged slice states impart distinct physiological parameters on brain tissue.

Changes in [K+]o evoked by baclofen in guinea pig hippocampus

1998 ◽  
Vol 76 (2) ◽  
pp. 148-154 ◽  
Author(s):  
G V Obrocea ◽  
Mary E Morris
Keyword(s):  
Guinea Pig ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Brain Slices ◽  
Field Potential ◽  
Stratum Radiatum ◽  
Extracellular Potassium ◽  
Receptor Subtype ◽  
Field Potentials ◽  
Stratum Pyramidale

K+-sensitive microelectrodes were used to record changes evoked by baclofen in extracellular potassium concentration ([K+]o) and field potentials in the stratum pyramidale (SP) and stratum radiatum (SR) in the CA1b region of guinea pig hippocampal slices in vitro. Bath applications of ( ±)-baclofen (1 µM - 3 mM for approx 5 min) evoked changes in [K+]o, which were in most cases sustained throughout agonist application and reversed during washout. The maximal (Rmax) values for curves fitted to the concentration-response data were for SP and SR, respectively, 0.59 ± 0.03 and 0.65 ± 0.03 mM, and EC50 values were 39.7 and 39.4 µM, respectively. The evoked K+ and field potential changes were significantly correlated and could be blocked by 2-OH-saclofen (50 µM) and CGP 35348 (50 µM). In <= 10% of experiments baclofen (10-50 µM) induced either a decrease or a transient increase ( <= 1 min duration) in [K+]o; in some slices with concentrations >=20 µM an initial decrease preceded a progressive increase. Pressure ejection of baclofen (100 µM for 100-900 ms) evoked increases in [K+]o and field potentials, which were larger in SR than in SP. In <= 10% of slices brief and (or) sustained application of baclofen (by either bath perfusion or pressure ejection) also evoked synchronous, repetitive interictal and ictal discharges at frequencies approx 1/s and 1/12 s, respectively, an observation that affirms a proconvulsant capacity. It is concluded that (i) although increases in [K+]o evoked by baclofen in SR compared with SP are slightly larger, they are not significantly different, (ii) GABAB receptor subtype(s) in SR and SP appear similar, as they have identical affinities, and (iii) [K+]o accumulations evoked by GABA likely include a contribution from a GABAB receptor activated K+ conductance, especially in dendritic regions.Key words: brain slices, stratum pyramidale, stratum radiatum, GABAB receptors, ion-selective microelectrodes, epileptiform activity.

Impact of Spontaneous Synaptic Activity on the Resting Properties of Cat Neocortical Pyramidal Neurons In Vivo

1998 ◽  
Vol 79 (3) ◽  
pp. 1450-1460 ◽  
Author(s):  
Denis Paré ◽  
Eric Shink ◽  
Hélène Gaudreau ◽  
Alain Destexhe ◽  
Eric J. Lang
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Synaptic Activity ◽  
Intact Brain ◽  
Lower Temperature ◽  
The Impact ◽  
Neocortical Pyramidal Neurons

Paré, Denis, Eric Shink, Hélène Gaudreau, Alain Destexhe, and Eric J. Lang. Impact of spontaneous synaptic activity on the resting properties of cat neocortical pyramidal neurons in vivo. J. Neurophysiol. 79: 1450–1460, 1998. The frequency of spontaneous synaptic events in vitro is probably lower than in vivo because of the reduced synaptic connectivity present in cortical slices and the lower temperature used during in vitro experiments. Because this reduction in background synaptic activity could modify the integrative properties of cortical neurons, we compared the impact of spontaneous synaptic events on the resting properties of intracellularly recorded pyramidal neurons in vivo and in vitro by blocking synaptic transmission with tetrodotoxin (TTX). The amount of synaptic activity was much lower in brain slices (at 34°C), as the standard deviation of the intracellular signal was 10–17 times lower in vitro than in vivo. Input resistances ( R ins) measured in vivo during relatively quiescent epochs (“control R ins”) could be reduced by up to 70% during periods of intense spontaneous activity. Further, the control R ins were increased by ∼30–70% after TTX application in vivo, approaching in vitro values. In contrast, TTX produced negligible R in changes in vitro (∼4%). These results indicate that, compared with the in vitro situation, the background synaptic activity present in intact networks dramatically reduces the electrical compactness of cortical neurons and modifies their integrative properties. The impact of the spontaneous synaptic bombardment should be taken into account when extrapolating in vitro findings to the intact brain.

Endogenous bursts underlie seizurelike activity in solitary excitatory hippocampal neurons in microcultures

1994 ◽  
Vol 72 (4) ◽  
pp. 1874-1884 ◽  
Author(s):  
M. M. Segal
Keyword(s):  
Action Potentials ◽  
Hippocampal Neurons ◽  
Epileptiform Activity ◽  
Brain Slices ◽  
Model System ◽  
Physiological Solution ◽  
Repetitive Firing ◽  
Extracellular Potassium ◽  
Glutamate Antagonists ◽  
Characteristic Type

1. I compared the relative contributions of synaptic potentials and endogenous bursting to seizurelike activity in a simple model system. The system consisted of a solitary excitatory hippocampal rat neuron in a microculture. Each solitary excitatory neuron was grown in kynurenate and elevated magnesium and had excitatory autapses. 2. In normal physiological solution most neurons displayed the characteristic type of interictal epileptiform activity, the paroxysmal depolarizing shift (PDS). A minority of neurons displayed ictuslike epileptiform activity consisting of runs of PDSs with a sustained neuronal depolarization. 3. I analyzed the synaptic and nonsynaptic components underlying these forms of epileptiform activity. The synaptic and calcium current components of the epileptiform activity were removed by using a “synapse blocking solution” in which calcium was replaced with magnesium, and glutamate receptor activity was blocked using the glutamate antagonists 2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione. Neurons that had only PDSs in normal physiological solution typically displayed only one or two action potentials in this synapse blocking solution. In contrast, neurons that had sustained depolarizations in normal physiological solution generally displayed bursts of action potentials in the synapse blocking solution, and some of the bursts had plateau depolarizations that lasted as long as several seconds. 4. The seconds-long endogenous plateau depolarizations were suppressed by tetrodotoxin, indicating involvement of persistent sodium currents. 5. The plateau depolarizations were shortened or abolished by 8 microM phenytoin, but there was only a small effect of phenytoin on nonplateau sustained repetitive firing of action potentials. 6. Elevation of extracellular potassium to 8 mM typically intensified the endogenous activity, usually converting action potential bursts to bursts with plateaus. 7. This study demonstrates that a sodium-dependent endogenous bursting underlies ictuslike epileptiform activity in this model system of seizurelike activity. The ability of phenytoin to attenuate this endogenous bursting suggests that a similar mechanism might underlie epileptiform bursting in less reduced systems such as brain slices or intact animals.

scholarly journals Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1625
Author(s):  
Theresa C. Sutherland ◽  
Arthur Sefiani ◽  
Darijana Horvat ◽  
Taylor E. Huntington ◽  
Yuanjiu Lei ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Traumatic Injury ◽  
Axon Growth ◽  
Neurite Growth ◽  
Growth Potential ◽  
Mitochondrial Functions ◽  
Cord Injury ◽  
Age Dependent ◽  
Mitochondria Functions ◽  
The Impact

The age of incidence of spinal cord injury (SCI) and the average age of people living with SCI is continuously increasing. However, SCI is extensively modeled in young adult animals, hampering translation of research to clinical applications. While there has been significant progress in manipulating axon growth after injury, the impact of aging is still unknown. Mitochondria are essential to successful neurite and axon growth, while aging is associated with a decline in mitochondrial functions. Using isolation and culture of adult cortical neurons, we analyzed mitochondrial changes in 2-, 6-, 12- and 18-month-old mice. We observed reduced neurite growth in older neurons. Older neurons also showed dysfunctional respiration, reduced membrane potential, and altered mitochondrial membrane transport proteins; however, mitochondrial DNA (mtDNA) abundance and cellular ATP were increased. Taken together, these data suggest that dysfunctional mitochondria in older neurons may be associated with the age-dependent reduction in neurite growth. Both normal aging and traumatic injury are associated with mitochondrial dysfunction, posing a challenge for an aging SCI population as the two elements can combine to worsen injury outcomes. The results of this study highlight this as an area of great interest in CNS trauma.

scholarly journals Moderately Inducing Autophagy Reduces Tertiary Brain Injury after Perinatal Hypoxia-Ischemia

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 898
Author(s):  
Brian H. Kim ◽  
Maciej Jeziorek ◽  
Hur Dolunay Kanal ◽  
Viorica Raluca Contu ◽  
Radek Dobrowolski ◽  
...  
Keyword(s):  
Cell Death ◽  
Structural Integrity ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Brain Slices ◽  
Brain Structures ◽  
Improved Outcomes ◽  
Hypoxia Ischemia ◽  
Tgfβ Receptor ◽  
Progressive Neurodegeneration

Recent studies of cerebral hypoxia-ischemia (HI) have highlighted slowly progressive neurodegeneration whose mechanisms remain elusive, but if blocked, could considerably improve long-term neurological function. We previously established that the cytokine transforming growth factor (TGF)β1 is highly elevated following HI and that delivering an antagonist for TGFβ receptor activin-like kinase 5 (ALK5)—SB505124—three days after injury in a rat model of moderate pre-term HI significantly preserved the structural integrity of the thalamus and hippocampus as well as neurological functions associated with those brain structures. To elucidate the mechanism whereby ALK5 inhibition reduces cell death, we assessed levels of autophagy markers in neurons and found that SB505124 increased numbers of autophagosomes and levels of lipidated light chain 3 (LC3), a key protein known to mediate autophagy. However, those studies did not determine whether (1) SB was acting directly on the CNS and (2) whether directly inducing autophagy could decrease cell death and improve outcome. Here we show that administering an ALK5 antagonist three days after HI reduced actively apoptotic cells by ~90% when assessed one week after injury. Ex vivo studies using the lysosomal inhibitor chloroquine confirmed that SB505124 enhanced autophagy flux in the injured hemisphere, with a significant accumulation of the autophagic proteins LC3 and p62 in SB505124 + chloroquine treated brain slices. We independently activated autophagy using the stimulatory peptide Tat-Beclin1 to determine if enhanced autophagy is directly responsible for improved outcomes. Administering Tat-Beclin1 starting three days after injury preserved the structural integrity of the hippocampus and thalamus with improved sensorimotor function. These data support the conclusion that intervening at this phase of injury represents a window of opportunity where stimulating autophagy is beneficial.

scholarly journals Association of epileptiform brain activity and specific language impairment (SLI) in preschool children

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Ahmed Esmael ◽  
Sara Elsherbeny ◽  
Mohammed Abbas
Keyword(s):  
Preschool Children ◽  
Language Impairment ◽  
Significant Relationship ◽  
Specific Language Impairment ◽  
Intelligence Quotient ◽  
Epileptiform Activity ◽  
Control Group ◽  
Specific Language ◽  
Cognitive Age ◽  
The Impact

Abstract Background Epileptiform activities can cause transient or permanent deficits that affect the children during development and may be accompanied by neurodevelopmental disorders like specific language impairment. Objectives The objective of this study was to find if there is a possible association and the impact of epilepsy and epileptiform activity in children with specific language impairment. Patients and methods The study was conducted on 80 children suffering from specific language impairment and 80 age and sex match healthy control children. Computed tomography brain was performed and electroencephalography was recorded for children. Intelligence quotient level, cognitive age, social, and phoniatric assessment were done for all patients. Results Eighty children with specific language impairment (51 males and 29 females) with a mean age of 4.11 ± 1.93. Patients with specific language impairment showed significantly higher rates of abnormal electroencephalography (P = 0.006) and epilepsy (P < 0.001) compared to the control group. Spearman correlation demonstrated a highly negative significant relationship linking the language, intelligence quotient with abnormal electroencephalography and epilepsy (r = − 0.91, P < 0.01 and r = − 0.91, P < 0.01 respectively). Also, there was a moderately inverse significant relationship linking the cognitive age, social with abnormal electroencephalography, and epilepsy (r = − 0.70, P < 0.05 and r = − 0.65, P < 0.05 respectively). Conclusion Epileptiform activities even without epilepsy in preschool children may alter normal language function. Specific language impairment was associated with lower intelligence quotient levels, social, and cognitive age. Trial registration ClinicalTrials.gov ID: NCT04141332

scholarly journals Neuromodulation of Astrocytic K+ Clearance

2021 ◽  
Vol 22 (5) ◽  
pp. 2520
Author(s):  
Alba Bellot-Saez ◽  
Rebecca Stevenson ◽  
Orsolya Kékesi ◽  
Evgeniia Samokhina ◽  
Yuval Ben-Abu ◽  
...  
Keyword(s):  
Oscillatory Behavior ◽  
Network Activity ◽  
Oscillatory Activity ◽  
Extracellular Potassium ◽  
Uptake Mechanism ◽  
Kir Channels ◽  
Neuronal Network Activity ◽  
Clearance Process ◽  
Spatial Buffering ◽  
The Impact

Potassium homeostasis is fundamental for brain function. Therefore, effective removal of excessive K+ from the synaptic cleft during neuronal activity is paramount. Astrocytes play a key role in K+ clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]o) or impairments of the astrocytic clearance mechanism affect the resonance and oscillatory behavior of both the individual and networks of neurons. These results indicate that astrocytes have the potential to modulate neuronal network activity, however, the cellular effectors that may affect the astrocytic K+ clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behavior, on the astrocytic clearance process. Our results suggest that while some neuromodulators (5-HT; NA) might affect astrocytic spatial buffering via gap-junctions, others (DA; Histamine) primarily affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to maximize the synchronous network activity.

scholarly journals Neuropathology of the Brainstem to Mechanistically Understand and to Treat Alzheimer’s Disease

2021 ◽  
Vol 10 (8) ◽  
pp. 1555
Author(s):  
Ágoston Patthy ◽  
János Murai ◽  
János Hanics ◽  
Anna Pintér ◽  
Péter Zahola ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Brain Structures ◽  
Specific Information ◽  
Cellular Mechanisms ◽  
Monoaminergic System ◽  
Monoaminergic Neurons

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder as yet without effective therapy. Symptoms of this disorder typically reflect cortical malfunction with local neurohistopathology, which biased investigators to search for focal triggers and molecular mechanisms. Cortex, however, receives massive afferents from caudal brain structures, which do not only convey specific information but powerfully tune ensemble activity. Moreover, there is evidence that the start of AD is subcortical. The brainstem harbors monoamine systems, which establish a dense innervation in both allo- and neocortex. Monoaminergic synapses can co-release neuropeptides either by precisely terminating on cortical neurons or, when being “en passant”, can instigate local volume transmission. Especially due to its early damage, malfunction of the ascending monoaminergic system emerges as an early sign and possible trigger of AD. This review summarizes the involvement and cascaded impairment of brainstem monoaminergic neurons in AD and discusses cellular mechanisms that lead to their dysfunction. We highlight the significance and therapeutic challenges of transmitter co-release in ascending activating system, describe the role and changes of local connections and distant afferents of brainstem nuclei in AD, and summon the rapidly increasing diagnostic window during the last few years.

Porphyromonas Gingivalis Infection Induces Synaptic Failure via Increased IL-1β Production in Leptomeningeal Cells

2021 ◽  
pp. 1-17
Author(s):  
Wanyi Huang ◽  
Fan Zeng ◽  
Yebo Gu ◽  
Muzhou Jiang ◽  
Xinwen Zhang ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Nlrp3 Inflammasome ◽  
Cortical Neurons ◽  
Inflammasome Activation ◽  
Memory Decline ◽  
Periodontal Bacteria ◽  
Nlrp3 Inflammasome Activation ◽  
Synaptic Failure ◽  
Pre Treatment ◽  
The Impact

Background: Studies have reported that synaptic failure occurs before the Alzheimer’s disease (AD) onset. The systemic Porphyromonas gingivalis (P. gingivalis) infection is involved in memory decline. We previously showed that leptomeningeal cells, covering the brain, activate glial cells by releasing IL-1β in response to systemic inflammation. Objective: In the present study, we focused on the impact of leptomeningeal cells on neurons during systemic P. gingivalis infection. Methods: The responses of leptomeningeal cells and cortical neurons to systemic P. gingivalis infection were examined in 15-month-old mice. The mechanism of IL-1β production by P. gingivalis infected leptomeningeal cells was examined, and primary cortical neurons were treated with P. gingivalis infected leptomeningeal cells condition medium (Pg LCM). Results: Systemic P. gingivalis infection increased the expression of IL-1β in leptomeninges and reduced the synaptophysin (SYP) expression in leptomeninges proximity cortex in mice. Leptomeningeal cells phagocytosed P. gingivalis resulting in lysosomal rupture and Cathepsin B (CatB) leakage. Leaked CatB mediated NLRP3 inflammasome activation inducing IL-1β secretion in leptomeningeal cells. Pg LCM decreased the expression of synaptic molecules, including SYP, which was inhibited by an IL-1 receptor antagonist pre-treatment. Conclusion: These observations demonstrate that P. gingivalis infection is involved in synaptic failure by inducing CatB/NLRP3 inflammasome-mediated IL-1β production in leptomeningeal cells. The periodontal bacteria-induced synaptic damage may accelerate the onset and cognitive decline of AD.

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