Cortical Interneurons Join the Mix in Absence Seizures
|
|
- Bruce Scott
- 6 years ago
- Views:
Transcription
1 Current Literature In Basic Science Cortical Interneurons Join the Mix in Absence Seizures CaV 2.1 Ablation in Cortical Interneurons Selectively Impairs Fast-Spiking Basket Cells and Causes Generalized Seizures. Rossignol E, Kruglikov I, van den Maagdenberg AM, Rudy B, Fishell G. Ann Neurol 2013;74: OBJECTIVE: Both the neuronal populations and mechanisms responsible for generalized spike-wave absence seizures are poorly understood. In mutant mice carrying loss-of-function (LOF) mutations in Cacna1a, which encodes the α1 pore-forming subunit of Ca V 2.1 (P/Q-type) voltage-gated Ca 2+ channels, generalized spike-wave seizures have been suggested to result from excessive bursting of thalamocortical cells. However, other cellular populations including cortical inhibitory interneurons may contribute to this phenotype. We investigated how different cortical interneuron subtypes are affected by the loss of Ca V 2.1 channel function and how this contributes to the onset of generalized epilepsy. METHODS: We designed genetic strategies to induce a selective Cacna1a LOF mutation in different cortical γ-aminobutyric acidergic (GABAergic) and/or glutamatergic neuronal populations in mice. We assessed the cellular and network consequences of these mutations by combining immunohistochemical assays, in vitro physiology, optogenetics, and in vivo video electroencephalographic recordings. RESULTS: We demonstrate that selective Cacna1a LOF from a subset of cortical interneurons, including parvalbumin (PV) + and somatostatin (SST) + interneurons, results in severe generalized epilepsy. Loss of Ca V 2.1 channel function compromises GABA release from PV + but not SST + interneurons. Moreover, thalamocortical projection neurons do not show enhanced bursting in these mutants, suggesting that this feature is not essential for the development of generalized spike-wave seizures. Notably, the concurrent removal of Ca V 2.1 channels in cortical pyramidal cells and interneurons considerably lessens seizure severity by decreasing cortical excitability. INTERPRETATION: Our findings demonstrate that conditional ablation of Ca V 2.1 channel function from cortical PV + interneurons alters GABA release from these cells, impairs their ability to constrain cortical pyramidal cell excitability, and is sufficient to cause generalized seizures. Epilepsy Currents, Vol. 14, No. 4 (July/August) 2014 pp American Epilepsy Society Commentary Absence seizures and other types of generalized seizures are characteristic of a number of classic epilepsy syndromes, such as childhood absence epilepsy and juvenile myoclonic epilepsy. Major advances in understanding the underlying neuroanatomy, pathophysiology, and molecular genetics of absence epilepsies have been made through decades of extensive clinical and basic research. However, significant unknowns and controversies about the pathogenesis of generalized seizures still exist, especially regarding the mechanisms of initiation of the seizures. A variety of rational candidates and hypotheses have been advanced in identifying the primary anatomic site, cell populations, and molecular mediators responsible for generating these seizures, but a unifying mechanism has not been established. The principal neuroanatomical networks mediating absence seizures are thought to involve reciprocal circuits between the thalamus and cortex. However, where within these circuits absence seizures are initially generated has been extensively debated, with different theories vacillating over time between cortex and thalamus (1). Early ideas, dating back to Penfield and Jasper in the mid-1900s, promoted the centrencephalic hypothesis that the thalamus could drive widespread cortical spike and wave discharges. The primary role of the thalamus was later supported by a variety of experimental studies implicating specific thalamic nuclei in generating both normal physiological rhythms, such as sleep spindles, and pathological oscillations of absence seizures (2). In contrast, other experimental evidence suggested that the cortex can be the primary initiator of generalized spikes and absence seizures. Combined cortical and subcortical depth electrode recordings indicated an earlier onset of spikes within the cortex in primate models of generalized epilepsy (1). More detailed quantitative analysis of cortical and thalamic recordings in a rodent genetic model of absence seizures has identified a focal region of somatosensory cortex as being the apparent trigger of generalized spike and wave activity (3). Finally, the corticoreticular concept of absence seizures incorporated aspects of both cortical and thalamic mechanisms with recurrent oscillations between these two regions, collectively forming the basis of absence seizures but with possible initiation in cortex. In dissecting the critical thalamocortical networks in more detail, the role of specific cell types, neurotransmitter 215
2 Cortical Interneurons and Absence Seizures systems, and ion channels in generating oscillatory physiological activity and generalized spike and wave discharges have been investigated. Long-range reciprocal connections between excitatory thalamocortical relay neurons in thalamic nuclei and widespread cortical pyramidal neurons projecting back to the thalamus constitute the primary circuit (2). Within the thalamus, additional local reciprocal connections between inhibitory GABAergic interneurons in the reticular nucleus and thalamocortical relay neurons may form a core unit capable of generating oscillations. In particular, cyclical bursting behavior in thalamocortical relay neurons may be triggered by low-voltage-activated T-type calcium channels in response to a rebound of the membrane potential following GABA interneuron-induced hyperpolarization. While intrinsic thalamic networks are firmly established as causing oscillatory, bursting patterns that promote normal sleep spindle activity, whether similar mechanisms also cause generalized spike and wave activity of absence seizures is hypothesized but not definitely proven. An increase in T- type calcium currents and tonic GABA inhibition in thalamic neurons associated with abnormal bursting in the thalamus has been detected in animal models as a potential cause of absence seizures (4, 5). However, even if thalamic-mediated bursting and oscillations promote absence seizures, it is still possible that a cortical source provides the initial stimulus triggering these oscillations. Compared with the thalamus, local circuits and mechanisms in the cortex that may generate corticothalamic oscillations are not as well defined. In addition to electrophysiological evidence for an earlier onset of generalized spike-and-wave activity in focal areas of the cortex, some mouse models of absence epilepsy exhibit reduced cortical inhibition, suggesting a defect in GABAergic interneurons (6). Furthermore, the identification of mutations in GABA receptors in human genetic absence epilepsies emphasizes the clinical relevance of GABAergic systems for generalized seizures (7, 8). With this background, the recent study by Rossignol and colleagues directly addresses the hypothesis that impairment of GABAergic interneurons in the cortex can lead to absence and other types of generalized seizures. They use targeted genetic techniques to inactivate the Ca v 2.1 P/Q-type calcium channel from specific populations of cortical GABAergic interneurons in transgenic mice. In comparison with the T-type calcium channel involved in generating oscillations, the P/Q-type channels are high-voltage gated calcium channels that primarily mediate presynaptic vesicular neurotransmitter release. In addition to localization within cortical neurons, Ca v 2.1 P/Q-type channels are abundantly found in cerebellar Purkinje neurons. As a result, patients and mouse models with Ca v 2.1 mutations exhibit ataxia, as well as absence seizures (9, 10). The study by Rossignol and colleagues bypasses the cerebellar involvement and focuses on cortical networks by utilizing advanced genetic inactivation strategies that specifically target cortical interneurons. The primary finding of this study that mice with loss of Ca v 2.1 channel function in cortical interneurons develop absence and other generalized seizures convincingly establishes that cortical interneuron dysfunction is sufficient to cause generalized seizures. In fact, one specific population of cortical GABAergic interneurons parvalbumin-positive fast-spiking neurons was implicated in causing generalized seizures. These fast-spiking interneurons exhibited impaired GABA release leading to disinhibition of cortical pyramidal neurons in these mice, whereas another major subtype of cortical interneuron was unaffected. In addition, there was no evidence of abnormal bursting of thalamocortical neurons, further emphasizing the primary importance of cortex over thalamus in this model. Although this study provides compelling evidence implicating cortical interneurons in generalized seizures, there are some caveats: Interestingly, the mouse model exhibited not only absence seizures but also a variety of other generalized seizure types, including myoclonic, tonic, and tonic clonic seizures. Thus, this is not a pure model of absence epilepsy and may not involve the same thalamocortical mechanisms that have been implicated in many other models primarily involving absence seizures, as indicated by the lack of abnormal bursting of thalamocortical neurons in the present model. In fact, this study should prompt deeper investigation of the role of cortical interneurons in contributing to absence seizures in other animal models that have focused more on thalamocortical oscillations. Ultimately, patients with absence seizures represent a heterogeneous group, with a variety of underlying genetic etiologies and associated epilepsy syndromes. Attempting to find unifying mechanisms for generalized seizures is a worthwhile but perhaps unrealistic goal. Between different patients and even within the same patient, it is likely that multiple mechanisms are differentially involved in various situations in generating generalized spike-and-wave discharges and generalized seizures. Multiple hubs within a diffuse, distributed network including both the cortex, thalamus, and other subcortical structures may be capable of triggering seizures within the network at any given time. The work by Rossignol and colleagues highlights the importance of the cortical interneuron and suggests potential therapeutic strategies for targeting this focal point. by Michael Wong, MD, PhD References 1. Avoli M. A brief history on the oscillating roles of thalamus and cortex in absence seizures. Epilepsia 2012;53: Beenhakker MP, Huguenard JR. Neurons that fire together also conspire together: Is normal sleep circuitry hijacked to generate epilepsy. Neuron 2012;62: Meeren HK, Pijn JP, Van Luijtelaar EL, Coenen AM, Lopes da Silva FH. Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. J Neurosci 2002;22: Tsakiridou E, Bertollini L, de Curtis M, Avanzini G, Pape HC. Selective increase in T-type calcium conductance of reticular thalamic neurons in a rat model of absence epilepsy. J Neurosci 1995;15: Cope DW, Di Giovanni G, Fyson SJ, Orban G, Errington AC, Lorincz ML, Gould TM, Carter DA, Crunelli V. Enhanced tonic GABAA inhibition in typical absence epilepsy. Nat Med 2009;15: Tan HO, Reid CA, Single FN, Davies PJ, Chiu C, Murphy S, Clarke AL, Dibbens L, Krestel H, Mulley JC, Jones MV, Seeburg PH, Sakmann B, 216
3 Cortical Interneurons and Absence Seizures Berkovic SF, Sprengel R, Petrou S. Reduced cortical inhibition in a mouse model of familial childhood absence epilepsy. Proc Natl Acad Sci USA 2007;104: Wallace RH, Marini C, Petrou S, Harkin LA, Bowser DN, Panchal RG, Williams DA, Sutherland GR, Mulley JC, Scheffer IE, Berokovic SF. Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures. Nat Genet 2001;28: Maljevic S, Krampfl K, Cobilanschi J, Tilgen N, Bever S, Weber YG, Schlesinger F, Ursu D, Melzer W, Cossette P, Bufler J, Lerche H, Heils A. A mutation in the GABA(A) receptor alpha(1)-subunit is associated with absence epilepsy. Ann Neurol 2006;59: Fletcher CF, Lutz CM, O Sullivan TN, Shaughnessy JD Jr, Hawkes R, Frankel WN, Copeland NG, Jenkins NA. Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell 1996;87: Imbrici P, Jaffe SL, Eunson LH, Davies NP, Herd C, Robertson R, Kullman DM, Hanna MG. Dysfunction of the brain calcium channel CaV2.1 in absence epilepsy and episodic ataxia. Brain 2004;127:
4 American Epilepsy Society Epilepsy Currents Journal Disclosure of Potential Conflicts of Interest Instructions The purpose of this form is to provide readers of your manuscript with information about your other interests that could influence how they receive and understand your work. Each author should submit a separate form and is responsible for the accuracy and completeness of the submitted information. The form is in four parts. 1. Identifying information. Enter your full name. If you are NOT the main contributing author, please check the box no and enter the name of the main contributing author in the space that appears. Provide the requested manuscript information. 2. The work under consideration for publication. This section asks for information about the work that you have submitted for publication. The time frame for this reporting is that of the work itself, from the initial conception and planning to the present. The requested information is about resources that you received, either directly or indirectly (via your institution), to enable you to complete the work. Checking No means that you did the work without receiving any financial support from any third party that is, the work was supported by funds from the same institution that pays your salary and that institution did not receive third-party funds with which to pay you. If you or your institution received funds from a third party to support the work, such as a government granting agency, charitable foundation or commercial sponsor, check Yes. Then complete the appropriate boxes to indicate the type of support and whether the payment went to you, or to your institution, or both. 3. Relevant financial activities outside the submitted work. This section asks about your financial relationships with entities in the bio-medical arena that could be perceived to influence, or that give the appearance of potentially influencing, what you wrote in the submitted work. For example, if your article is about testing an epidermal growth factor receptor (DGFR) antagonist in lung cancer, you should report all associations with entities pursuing diagnostic or therapeutic strategies in cancer in general, not just in the area of EGFR or lung cancer. Report all sources of revenue paid (or promised to be paid) directly to you or your institution on your behalf over the 36 months prior to submission of the work. This should include all monies from sources with relevance to the submitted work, not just monies from the entity that sponsored the research. Please note that your interactions with the work s sponsor that are outside the submitted work should also be listed here. If there is any question, it is usually better to disclose a relationship than not to do so. For grants you have received for work outside the submitted work, you should disclose support ONLY from entities that could be perceived to be affected financially by the published work, such as drug companies, or foundations supported by entities that could be perceived to have a financial stake in the outcome. Public funding sources, such as government agencies, charitable foundations or academic institutions, need not be disclosed. For example, if a government agency sponsored a study in which you have been involved and drugs were provided by a pharmaceutical company, you need only list the pharmaceutical company. 4. Other relationships Use this section to report other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing, what you wrote in the submitted work.
5 American Epilepsy Society Epilepsy Currents Journal Disclosure of Potential Conflicts of Interest Section #1 Identifying Information 1. Today s Date: 1/2/ First Name Michael Last Name Wong Degree MD, PhD 3. Are you the Main Assigned Author? Yes No If no, enter your name as co-author: 4. Manuscript/Article Title: Cortical Interneurons Join the Mix in Absence Seizures 5. Journal Issue you are submitting for: 14.4 Section #2 The Work Under Consideration for Publication Did you or your institution at any time receive payment or services from a third party for any aspect of the submitted work (including but not limited to grants, data monitoring board, study design, manuscript preparation, statistical analysis, etc.)? Complete each row by checking No or providing the requested information. If you have more than one relationship just add rows to this table. Type No Money Paid to You Money to Your Institution* Name of Entity Comments** 1. Grant 2. Consulting fee or honorarium 3. Support for travel to meetings for the study or other purposes 4. Fees for participating in review activities such as data monitoring boards, statistical analysis, end point committees, and the like 5. Payment for writing or reviewing the manuscript 6. Provision of writing assistance, medicines, equipment, or administrative support. 7. Other * This means money that your institution received for your efforts on this study. ** Use this section to provide any needed explanation. Page 2 8/11/2014
6 Section #3 Relevant financial activities outside the submitted work. Place a check in the appropriate boxes in the table to indicate whether you have financial relationships (regardless of amount of compensation) with entities as described in the instructions. Use one line for each entity; add as many lines as you need by clicking the Add box. You should report relationships that were present during the 36 months prior to submission. Complete each row by checking No or providing the requested information. If you have more than one relationship just add rows to this table. Type of relationship (in alphabetical order) No Name of Entity Comments** 1. Board membership 2. Consultancy 3. Employment 4. Expert testimony Money Paid to You Money to Your Institution* 5. Grants/grants pending National Institutes of Health 6. Payment for lectures including service on speakers bureaus 7. Payment for manuscript preparation. 8. Patents (planned, pending or issued) 9. Royalties 10. Payment for development of educational presentations 11. Stock/stock options 12. Travel/accommodations/meeti ng expenses unrelated to activities listed.** 13. Other (err on the side of full disclosure) Department of Defense * This means money that your institution received for your efforts. ** For example, if you report a consultancy above there is no need to report travel related to that consultancy on this line. Section #4 Other relationships Are there other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing, what you wrote in the submitted work? No other relationships/conditions/circumstances that present a potential conflict of interest. Yes, the following relationships/conditions/circumstances are present: Page 3 8/11/2014
7 Thank you for your assistance. Epilepsy Currents Editorial Board Page 4 8/11/2014
Treatment of Super-Refractory Status Epilepticus: The Sooner the Better with Less Adverse Effects
Treatment of Super-Refractory Status Epilepticus: The Sooner the Better with Less Adverse Effects Current Literature In Clinical Science Efficacy and Safety of Ketamine in Refractory Status Epilepticus.
More informationEEG Wave of the Future: The Video-EEG and fmri Suite?
Current Literature In Clinical Science EEG Wave of the Future: The Video-EEG and fmri Suite? Mapping Preictal and Ictal Haemodynamic Networks Using Video-Electroencephalography and Functional Imaging.
More informationHow Deactivating an Inhibitor Causes Absence Epilepsy: Validation of a Noble Lie
Current Literature In Basic Science How Deactivating an Inhibitor Causes Absence Epilepsy: Validation of a Noble Lie A New Mode of Corticothalamic Transmission Revealed in the Gria4 / Model of Absence
More informationB(I)RD Watching: A Way to Stratify Seizure Risk?
B(I)RD Watching: A Way to Stratify Seizure Risk? Current Literature In Clinical Science Brief Potentially Ictal Rhythmic Discharges in Critically Ill Adults. Yoo JY, Rampal N, Petroff OA, Hirsch LJ, Gaspard
More informationThe Heat is On: L-type Calcium Channels and Febrile Seizures
The Heat is On: L-type Calcium Channels and Febrile Seizures Current Literature In Basic Science Temperature-Sensitive Cav1.2 Calcium Channels Support Intrinsic Firing of Pyramidal Neurons and Provide
More informationTurning Up the Heat on the Impact of Febrile Status Epilepticus
Current Literature In Clinical Science Turning Up the Heat on the Impact of Febrile Status Epilepticus MRI Abnormalities Following Febrile Status Epilepticus in Children: The FEBSTAT Study. Shinnar S,
More informationGhee Whiz! The Growing Evidence for the Benefits of the Modified Atkins Diet
Current Literature In Clinical Science Ghee Whiz! The Growing Evidence for the Benefits of the Modified Atkins Diet Use of the Modified Atkins Diet for Treatment of Refractory Childhood Epilepsy: A Randomized
More informationEarly Influences: Seizures During Infancy Influence Behavior in Young Adult Mice
Early Influences: Seizures During Infancy Influence Behavior in Young Adult Mice Current Literature In Basic Science Early-Life Seizures Result in Deficits in Social Behavior and Learning. Lugo JN, Swann
More informationDravet in the Dish: Mechanisms of Hyperexcitability
Current Literature In Basic Science Dravet in the Dish: Mechanisms of Hyperexcitability Purinergic Control of Hippocampal Circuit Hyperexcitability in Dravet Syndrome. Gu F, Hazra A, Aulakh A, Ziburkus
More informationStay, Hit, or Fold? What Do You Do If the Treatment May Be as Bad as the Problem Results of a Q-PULSE Survey
It s Current Epilepsy Resources and Updates Stay, Hit, or Fold? What Do You Do If the Treatment May Be as Bad as the Problem Results of a Q-PULSE Survey Chad Carlson, MD Associate Professor of Neurology,
More informationSUDEP: Sudden Unexpected Death in Epilepsy on Placebo?
Current Literature In Clinical Science SUDEP: Sudden Unexpected Death in Epilepsy on Placebo? Risk of Sudden Unexpected Death in Epilepsy in Patients Given Adjunctive Antiepileptic Treatment for Refractory
More informationCan Status Epilepticus Sometimes Just Be a Long Seizure?
Current Literature In Clinical Science Can Status Epilepticus Sometimes Just Be a Long Seizure? Unprovoked Status Epilepticus: The Prognosis for Otherwise Normal Children With Focal Epilepsy. Camfield
More informationChanging Name of Epilepsy in Korea; Cerebroelectric Disorder (noi-jeon-jeung,,): My Epilepsy Story.
Current Literature In Clinical Science Sticks and Stones Changing Name of Epilepsy in Korea; Cerebroelectric Disorder (noi-jeon-jeung,,): My Epilepsy Story. Kim HD, Kang HC, Lee SA, Huh K, Lee BI. Epilepsia
More informationNeurostimulation for Epilepsy: Do We Know the Best Stimulation Parameters?
Neurostimulation for Epilepsy: Do We Know the Best Stimulation Parameters? Current Literature In Basic Science Effect of Stimulus Parameters in the Treatment of Seizures by Electrical Stimulation in the
More informationPerampanel: Getting AMPed for AMPA Targets
Perampanel: Getting AMPed for AMPA Targets Current Literature In Clinical Science Randomized Phase III Study 306: Adjunctive Perampanel for Refractory Partial-Onset Seizures. Krauss GL, Serratosa JM, Villanueva
More informationFemale Hormones Prevent a Catastrophic Epilepsy in Male Mice
Current Literature In Basic Science Female Hormones Prevent a Catastrophic Epilepsy in Male Mice Neonatal Estradiol Stimulation Prevents Epilepsy in Arx Model of X-linked Infantile Spasms Syndrome. Olivetti
More informationSudden Unexpected Death in Dravet Syndrome
Current Literature In Basic Science Sudden Unexpected Death in Dravet Syndrome Sudden Unexpected Death in a Mouse Model of Dravet Syndrome. Kalume F, Westenbroeck RE, Cheah CS, Yu FH, Oakley JC, Scheuer
More informationZonisamide Should Be Considered a First-Line Antiepileptic Drug for Patients with Newly Diagnosed Partial Epilepsy
Current Literature In Clinical Science Zonisamide Should Be Considered a First-Line Antiepileptic Drug for Patients with Newly Diagnosed Partial Epilepsy Efficacy and Tolerability of Zonisamide Versus
More informationVoltage-Gated Ion Channel Accessory Subunits: Sodium, Potassium, or Both?
Current Literature In Basic Science Voltage-Gated Ion Channel Accessory Subunits: Sodium, Potassium, or Both? The Sodium Channel Accessory Subunit Navβ1 Regulates Neuronal Excitability through Modulation
More informationA Shot in the Arm for Prehospital Status Epilepticus: The RAMPART Study
Current Literature In Clinical Science A Shot in the Arm for Prehospital Status Epilepticus: The RAMPART Study Intramuscular Versus Intravenous Therapy for Prehospital Status Epilepticus. Silbergleit R,
More informationRapamycin Attenuates the Development of Posttraumatic Epilepsy in a Mouse Model of Traumatic Brain Injury.
Current Literature In Basic Science Prophylaxis for Post-Traumatic Epilepsy: Can Your Kinase Do That? Rapamycin Attenuates the Development of Posttraumatic Epilepsy in a Mouse Model of Traumatic Brain
More informationNeuronal Firing in Human Epileptic Cortex: The Ins and Outs of Synchrony During Seizures
Current Literature In Basic Science Neuronal Firing in Human Epileptic Cortex: The Ins and Outs of Synchrony During Seizures Evidence of an inhibitory restraint of seizure activity in humans. Schevon CA,
More informationMechanisms of Seizure-Induced Inflammation of the Brain: Many Possible Roles for Neuronal COX-2
Current Literature In Basic Science Mechanisms of Seizure-Induced Inflammation of the Brain: Many Possible Roles for Neuronal COX-2 Ablation of Cyclooxygenase-2 in Forebrain Neurons is Neuroprotective
More informationChloride s Exciting Role in Neonatal Seizures Suggests Novel Therapeutic Approach
Current Literature In Basic Science Chloride s Exciting Role in Neonatal Seizures Suggests Novel Therapeutic Approach Progressive NKCC1-Dependent Neuronal Chloride Accumulation During Neonatal Seizures.
More informationThe Fat Is in the Fire: Ketogenic Diet for Refractory Status Epilepticus
Current Literature In Clinical Science The Fat Is in the Fire: Ketogenic Diet for Refractory Status Epilepticus Efficacy of Ketogenic Diet in Severe Refractory Status Epilepticus Initiating Fever Induced
More informationPretreatment EEG in Childhood Absence Epilepsy: Associations With Attention and Treatment Outcome.
Current Literature In Clinical Science Childhood Absence Epilepsy: What Is All the Distraction About? Pretreatment EEG in Childhood Absence Epilepsy: Associations With Attention and Treatment Outcome.
More informationThe Role of EEG After Cardiac Arrest and Hypothermia
Current Literature In Clinical Science The Role of EEG After Cardiac Arrest and Hypothermia Continuous EEG in Therapeutic Hypothermia After Cardiac Arrest: Prognostic and Clinical Value. Crepeau AZ, Rabinstein
More informationStEPing EP2 to Prevent Status Epilepticus Induced Mortality and Inflammation
Current Literature In Basic Science StEPing EP2 to Prevent Status Epilepticus Induced Mortality and Inflammation Inhibition of the Prostaglandin Receptor EP2 Following Status Epilepticus Reduces Delayed
More informationParadox Lost: Exploring the Clinical-Radiologic Dissociation Seen in Anti-NMDA Receptor Encephalitis
Current Literature In Clinical Science Paradox Lost: Exploring the Clinical-Radiologic Dissociation Seen in Anti-NMDA Receptor Encephalitis Functional and Structural Brain Changes in Anti N-Methyl-D-Aspartate
More informationLevetiracetam: More Evidence of Safety in Pregnancy
Current Literature In Clinical Science Levetiracetam: More Evidence of Safety in Pregnancy Levetiracetam in Pregnancy: Results From the UK and Ireland Epilepsy and Pregnancy Registers. Mawhinney E, Craig
More informationGlowing Feet Control the Blood of Seizures
Current Literature In Basic Science Glowing Feet Control the Blood of Seizures Ictal but Not Interictal Epileptic Discharges Activate Astrocyte Endfeet and Elicit Cerebral Arteriole Responses. Gómez-Gonzalo
More informationImproving Patient-Centered Care Coordination for Children With Epilepsy: Version 2.0 Upgrade Required
Current Literature In Clinical Science Improving Patient-Centered Care Coordination for Children With Epilepsy: Version 2.0 Upgrade Required Assessing Systems of Care for US Children With Epilepsy/Seizure
More informationDifficult-to-Localize Intractable Focal Epilepsy: An In-Depth Look
Current Literature In Clinical Science Difficult-to-Localize Intractable Focal Epilepsy: An In-Depth Look Stereoelectroencephalography in the Difficult to Localize Refractory Focal Epilepsy: Early Experience
More informationNeuropathology of the Blood-Brain Barrier in Epilepsy: Support to the Transport Hypothesis of Pharmacoresistance
Neuropathology of the Blood-Brain Barrier in Epilepsy: Support to the Transport Hypothesis of Pharmacoresistance Current Literature In Clinical Science Neuropathology of the Blood-Brain Barrier and Pharmaco-Resistance
More informationCurrent Literature In Clinical Science. Seizures and Strokes for Certain Folks. Incidence and Predictors of Acute Symptomatic Seizures After Stroke.
Current Literature In Clinical Science Seizures and Strokes for Certain Folks Incidence and Predictors of Acute Symptomatic Seizures After Stroke. Beghi E, D Alessandro R, Beretta S, Consoli D, Crespi
More informationHow Do Clinicians Adjust Lamotrigine Doses and Use Lamotrigine Blood Levels? A Q-PULSE Survey
It s Current Epilepsy Resources and Updates How Do Clinicians Adjust Lamotrigine Doses and Use Lamotrigine Blood Levels? A Q-PULSE Survey Michael Privitera, MD, 1 Timothy Welty, PharmD, 2 Barry Gidal,
More informationCurrent Literature In Clinical Science. Temporal Lobectomies in Children: More Than Just for Seizure Control?
Current Literature In Clinical Science Temporal Lobectomies in Children: More Than Just for Seizure Control? Long-Term Intellectual Outcome After Temporal Lobe Surgery in Childhood. Skirrow C, Cross JH,
More informationOptical Control of Focal Epilepsy in vivo with Caged Gamma-Aminobutyric Acid.
Current Literature In Basic Science Shining Light on Epilepsy: Optical Approaches for Treating Seizures Optical Control of Focal Epilepsy in vivo with Caged Gamma-Aminobutyric Acid. Yang X, Rode DL, Peterka
More informationGalanin Receptor 1 Deletion Exacerbates Hippocampal Neuronal Loss After Systemic Kainate Administration in Mice.
Current Literature In Basic Science Galanin Receptors Modulate Seizures Galanin Receptor 1 Deletion Exacerbates Hippocampal Neuronal Loss After Systemic Kainate Administration in Mice. Schauwecker PE.
More informationLicense to Ill: Playing the Odds After Withdrawing and Restarting Antiepileptic Drugs
License to Ill: Playing the Odds After Withdrawing and Restarting Antiepileptic Drugs Current Literature In Clinical Science Seizure Recurrence After Antiepileptic Drug Withdrawal and the Implications
More informationThis Is Your Brain on Drugs: Predicting Anticonvulsant Effect Using Transcranial Stimulation
Current Literature In Clinical Science This Is Your Brain on Drugs: Predicting Anticonvulsant Effect Using Transcranial Stimulation Predicting Seizure Control: Cortical Excitability and Antiepileptic Medication.
More informationRecipes for Making Human Interneurons from Stem Cells Require Multiple Factors, Careful Timing, and Long Maturation Periods
Current Literature In Basic Science Recipes for Making Human Interneurons from Stem Cells Require Multiple Factors, Careful Timing, and Long Maturation Periods Directed Differentiation and Functional Maturation
More informationCognitive and Behavioral Comorbidities in Epilepsy: The Treacherous Nature of Animal Models
Current Literature In Basic Science Cognitive and Behavioral Comorbidities in Epilepsy: The Treacherous Nature of Animal Models Different Emotional Disturbances in Two Experimental Models of Temporal Lobe
More informationStrain- and Age-Dependent Hippocampal Neuron Sodium Currents Correlate With Epilepsy Severity in Dravet Syndrome Mice.
Current Literature In Basic Science It Was the Interneuron With the Parvalbumin in the Hippocampus! No, It Was the Pyramidal Cell With the Glutamate in the Cortex! Searching for Clues to the Mechanism
More informationAre HFOs Still UFOs? The Known and Unknown About High Frequency Oscillations in Epilepsy Surgery
Current Literature In Clinical Science Are HFOs Still UFOs? The Known and Unknown About High Frequency Oscillations in Epilepsy Surgery High-Frequency Oscillations, Extent of Surgical Resection, and Surgical
More informationHope for New Treatments for Acute Repetitive Seizures
Current Literature In Clinical Science Hope for New Treatments for Acute Repetitive Seizures A Double-Blind, Randomized, Placebo-Controlled Trial of a Diazepam Auto-Injector Administered by Caregivers
More informationPharmacoresistance and Cognitive Delays in Children: A Bidirectional Relationship
Current Literature In Clinical Science Pharmacoresistance and Cognitive Delays in Children: A Bidirectional Relationship Age at Onset of Epilepsy, Pharmacoresistance, and Cognitive Outcomes: A Prospective
More informationEmbryological origin of thalamus
diencephalon Embryological origin of thalamus The diencephalon gives rise to the: Thalamus Epithalamus (pineal gland, habenula, paraventricular n.) Hypothalamus Subthalamus (Subthalamic nuclei) The Thalamus:
More informationA Lesson from The Brodie Ultimatum : The Locus of Control for Epilepsy is Outside the Therapeutic Alliance
Current Literature In Clinical Science A Lesson from The Brodie Ultimatum : The Locus of Control for Epilepsy is Outside the Therapeutic Alliance Patterns of treatment response in newly diagnosed epilepsy.
More informationNormal brain rhythms and the transition to epileptic activity
School on Modelling, Automation and Control of Physiological variables at the Faculty of Science, University of Porto 2-3 May, 2007 Topics on Biomedical Systems Modelling: transition to epileptic activity
More informationChopping Out CHOP Chops the Fate of Neurons
Chopping Out CHOP Chops the Fate of Neurons Current Literature In Basic Science CHOP Regulates the P53 MDM2 Axis and is Required for Neuronal Survival After Seizures. Engel T, Sanz-Rodgriguez A, Jimenez-Mateos
More informationPyramidal Neuron Axon Initial Segment Dysregulation in Nav β1 Subunit Epilepsy: A Tip of the Iceberg?
Current Literature In Basic Science Pyramidal Neuron Axon Initial Segment Dysregulation in Nav β1 Subunit Epilepsy: A Tip of the Iceberg? Axon Initial Segment Dysfunction in a Mouse Model of Genetic Epilepsy
More informationTolner EA, Hochman DW, Hassinen P, Otáhal J, Gaily E, Haglund MM, Kubová H, Schuchmann S, Vanhatalo S, Kaila K. Epilepsia 2011;52(1):
Current Literature In Clinical Science Stopping Seizures With Carbon Dioide Five Percent CO 2 Is a Potent, Fast-Acting Inhalation Anticonvulsant. Tolner EA, Hochman DW, Hassinen P, Otáhal J, Gaily E, Haglund
More informationMonotherapy in Newly Diagnosed Epilepsy: Levetiracetam Versus Standard Anticonvulsants
Monotherapy in Newly Diagnosed Epilepsy: Levetiracetam Versus Standard Anticonvulsants Current Literature In Clinical Science KOMET: An Unblinded, Randomised, Two Parallel-Group, Stratified Trial Comparing
More informationCortico-Thalamic Connections and Temporal Lobe Epilepsy: An Evolving Story
Current Literature In Clinical Science Cortico-Thalamic Connections and Temporal Lobe Epilepsy: An Evolving Story Mapping Thalamocortical Network Pathology in Temporal Lobe Epilepsy. Bernhardt BC, Bernasconi
More informationConfirmed! Durable Benefits of Epilepsy Surgery
Current Literature In Clinical Science Confirmed! Durable Benefits of Epilepsy Surgery Long-Term Outcomes of Epilepsy Surgery in Sweden: A National Prospective and Longitudinal Study. Edelvik A, Rydenhag
More informationCognitive Activation of Hyperexcitable Cortex in JME: Can It Trigger Seizures?
Current Literature In Clinical Science Cognitive Activation of Hyperexcitable Cortex in JME: Can It Trigger Seizures? Motor System Hyperconnectivity in Juvenile Myoclonic Epilepsy: A Cognitive Functional
More informationAntiepileptic agents
Antiepileptic agents Excessive excitability of neurons in the CNS Abnormal function of ion channels Spread through neural networks Abnormal neural activity leads to abnormal motor activity Suppression
More informationCurrent Literature In Clinical Science. Predicting Seizures: Are We There Yet?
Current Literature In Clinical Science Predicting Seizures: Are We There Yet? Prediction of Seizure Likelihood with a Long-Term, Implanted Seizure Advisory System in Patients with Drug- Resistant Epilepsy:
More informationSudden Unexpected Death in the Epilepsy Monitoring Unit
Current Literature In Clinical Science Sudden Unexpected Death in the Epilepsy Monitoring Unit Incidence and Mechanisms of Cardiorespiratory Arrests in Epilepsy Monitoring Units (MORTEMUS): A Retrospective
More informationLess is More: Reducing Tau Ameliorates Seizures in Epilepsy Models
Current Literature In Basic Science Less is More: Reducing Tau Ameliorates Seizures in Epilepsy Models Tau Loss Attenuates Neuronal Network Hyperexcitability in Mouse and Drosophila Genetic Models of Epilepsy.
More informationFour main theories on the pathophysiology of generalized absence seizures have been
NEUROLOGICAL REVIEW Evolving Concepts on the Pathophysiology of Absence Seizures The Cortical Focus Theory Hanneke Meeren, PhD; Gilles van Luijtelaar, PhD; Fernando Lopes da Silva, MD; Anton Coenen, PhD
More informationAnxiety Disorders in Epilepsy: The Forgotten Psychiatric Comorbidity
Current Literature In Clinical Science Aniety Disorders in Epilepsy: The Forgotten Psychiatric Comorbidity Prevalence of Aniety Disorders in Patients With Refractory Focal Epilepsy A Prospective Clinic
More informationReciprocal inhibition controls the oscillatory state in thalamic networks
Neurocomputing 44 46 (2002) 653 659 www.elsevier.com/locate/neucom Reciprocal inhibition controls the oscillatory state in thalamic networks Vikaas S. Sohal, John R. Huguenard Department of Neurology and
More informationDeep White Matter Track Record of Functional Integrity in Childhood Absence Epilepsy
Current Literature In Clinical Science Deep White Matter Track Record of Functional Integrity in Childhood Absence Epilepsy White Matter Impairment in the Basal Ganglia-Thalamocortical Circuit of Drug-Naïve
More informationPrimum Non Nocere: Are Seizure Medications Safe in Neonates?
Primum Non Nocere: Are Seizure Medications Safe in Neonates? Current Literature In Basic Science Neonatal Exposure to Antiepileptic Drugs Disrupts Striatal Synaptic Development. Forcelli PA, Janssen MJ,
More informationNeuroscience of Consciousness I
1 C83MAB: Mind and Brain Neuroscience of Consciousness I Tobias Bast, School of Psychology, University of Nottingham 2 What is consciousness? 3 Consciousness State of consciousness - Being awake/alert/attentive/responsive
More informationFebrile Seizures Research Is Really Heating Up!
Current Literature In Basic Science Febrile Seizures Research Is Really Heating Up! Epileptogenesis Provoked by Prolonged Eperimental Febrile Seizures: Mechanisms and Biomarkers. Dubé CM, Ravizza T, Hamamura
More informationHow to Advance the Debate on Nonspecific vs Specific Seizure Type and Comorbidity Profile
Current Literature In Clinical Science How to Advance the Debate on Nonspecific vs Specific Seizure Type and Comorbidity Profile Risk-Taking Behavior in Juvenile Myoclonic Epilepsy. Wandschneider, B, Centeno,
More informationBasic Mechanism for Generation of Brain Rhythms
203 Continuing Medical Education Basic Mechanism for Generation of Brain Rhythms Wei-Hung Chen Abstract- Study of the basic mechanism of brain rhythms adds to our understanding of the underlying processes
More informationFindings from the FEBSTAT Study: Can Observations After a Provoked Seizure Occurrence Have Broad Implications for Epileptogenesis?
Current Literature In Clinical Science Findings from the FEBSTAT Study: Can Observations After a Provoked Seizure Occurrence Have Broad Implications for Epileptogenesis? Human Herpesvirus 6 and 7 in Febrile
More informationDistinct Mechanisms Mediate Interictal and Pre-Ictal Discharges in Human Temporal Lobe Epilepsy
Current Literature In Basic Science Distinct Mechanisms Mediate Interictal and Pre-Ictal Discharges in Human Temporal Lobe Epilepsy Glutamatergic Pre-ictal Discharges Emerge at the Transition to Seizure
More informationAutoimmune Epilepsy: Are We Seeing the Tip of the Iceberg... or the Whole Thing?
Current Literature In Clinical Science Autoimmune Epilepsy: Are We Seeing the Tip of the Iceberg... or the Whole Thing? Autoimmune Epilepsy: Clinical Characteristics and Response to Immunotherapy. Quek
More informationThalamo-Cortical Relationships Ultrastructure of Thalamic Synaptic Glomerulus
Central Visual Pathways V1/2 NEUR 3001 dvanced Visual Neuroscience The Lateral Geniculate Nucleus () is more than a relay station LP SC Professor Tom Salt UCL Institute of Ophthalmology Retina t.salt@ucl.ac.uk
More informationIs Focal Cortical Dysplasia an Infectious Disease?
Current Literature In Basic Science Is Focal Cortical Dysplasia an Infectious Disease? Detection of Human Papillomavirus in Human Focal Cortical Dysplasia Type IIB. Chen J, Tsai V, Parker WE, Aronica E,
More informationThe Hippocampus Participates in a Pharmacological Rat Model of Absence Seizures
Western University Scholarship@Western Electronic Thesis and Dissertation Repository January 2014 The Hippocampus Participates in a Pharmacological Rat Model of Absence Seizures Justin Andrew Arcaro The
More informationNeuregulation: NRG1 Tames Interneurons and Epilepsy
Current Literature In Basic Science Neuregulation: NRG1 Tames Interneurons and Epilepsy Neuregulin 1 Regulates Ecitability of Fast-Spiking Neurons Through Kv1.1 and Acts in Epilepsy. Li KX, Lu YM, Xu ZH,
More informationSLEEP AND AROUSAL: Thalamocortical Mechanisms
Annu. Rev. Neurosci. 1997. 20:185 215 Copyright c 1997 by Annual Reviews Inc. All rights reserved SLEEP AND AROUSAL: Thalamocortical Mechanisms David A. McCormick and Thierry Bal 1 Section of Neurobiology,
More informationEffects of Inhibitory Synaptic Current Parameters on Thalamocortical Oscillations
Effects of Inhibitory Synaptic Current Parameters on Thalamocortical Oscillations 1 2 3 4 5 Scott Cole Richard Gao Neurosciences Graduate Program Department of Cognitive Science University of California,
More informationCombining Ubiquitin Deficiency and GABA-Mediated Inhibition Equals Seizures?
Current Literature In Basic Science Combining Ubiquitin Deficiency and GABA-Mediated Inhibition Equals Seizures? Altered Ultrasonic Vocalization and Impaired Learning and Memory in Angelman Syndrome Mouse
More informationObjectives. brain pacemaker circuits role of inhibition
Brain Rhythms Michael O. Poulter, Ph.D. Professor, Molecular Brain Research Group Robarts Research Institute Depts of Physiology & Pharmacology, Clinical Neurological Sciences Schulich School of Medicine
More informationGenotype & Phenotype of Ohtahara Syndrome What s SCN2A Got to Do With It? A Clinician s Read
Current Literature In Clinical Science Genotype & Phenotype of Ohtahara Syndrome What s SCN2A Got to Do With It? A Clinician s Read Clinical Spectrum of SCN2A Mutations Expanding to Ohtahara Syndrome.
More informationWhen cells are already maximally potentiated LTP is occluded.
When cells are already maximally potentiated LTP is occluded. Stein, V et al., (2003) J Neurosci, 23:5503-6606. Also found in Rat Barrel Cortex Ehrlich & Malinow (2004) J. Neurosci. 24:916-927 Over-expression
More informationThalamocortical Dysrhythmia. Thalamocortical Fibers. Thalamocortical Loops and Information Processing
halamocortical Loops and Information Processing 2427 halamocortical Dysrhythmia Synonyms CD A pathophysiological chain reaction at the origin of neurogenic pain. It consists of: 1) a reduction of excitatory
More informationHHS Public Access Author manuscript Nat Neurosci. Author manuscript; available in PMC 2014 September 19.
Selective optical drive of thalamic reticular nucleus generates thalamic bursts & cortical spindles Michael M. Halassa 1,2,4, Joshua H. Siegle 2,4, Jason T. Ritt 3, Jonathan T. Ting 2, Guoping Feng 2,
More informationAnatomical and physiological considerations in thalamic rhythm generation
J. Sleep Res. (1998) 7, Suppl. 1, 24±29 Anatomical and physiological considerations in thalamic rhythm generation JOHN R. HUGUENARD Department of Neurology and Neurological Sciences, Stanford University
More informationNeuroscience: Exploring the Brain, 3e. Chapter 4: The action potential
Neuroscience: Exploring the Brain, 3e Chapter 4: The action potential Introduction Action Potential in the Nervous System Conveys information over long distances Action potential Initiated in the axon
More informationCurrent Literature In Clinical Science. Epilepsy Is Not Resolved. A Practical Clinical Definition of Epilepsy.
Current Literature In Clinical Science Epilepsy Is Not Resolved A Practical Clinical Definition of Epilepsy. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J Jr, Forsgren L,
More informationWhat Is a Seizure? Insights From Human Single-Neuron Recordings
What Is a Seizure? Insights From Human Single-Neuron Recordings Current Literature In Clinical Science Single-Neuron Dynamics in Human Focal Epilepsy. Truccolo W, Donoghue JA, Hochberg LR, Eskandar EN,
More informationCOGNITIVE SCIENCE 107A. Sensory Physiology and the Thalamus. Jaime A. Pineda, Ph.D.
COGNITIVE SCIENCE 107A Sensory Physiology and the Thalamus Jaime A. Pineda, Ph.D. Sensory Physiology Energies (light, sound, sensation, smell, taste) Pre neural apparatus (collects, filters, amplifies)
More informationP-glycoprotein Expression and Pharmacoresistant Epilepsy: Cause or Consequence?
Current Literature In Clinical Science P-glycoprotein Expression and Pharmacoresistant Epilepsy: Cause or Consequence? P-glycoprotein Expression and Function in Patients With Temporal Lobe Epilepsy: A
More information*Pathophysiology of. Epilepsy
*Pathophysiology of Epilepsy *Objectives * At the end of this lecture the students should be able to:- 1.Define Epilepsy 2.Etio-pathology of Epilepsy 3.Types of Epilepsy 4.Role of Genetic in Epilepsy 5.Clinical
More informationThe Role of Mitral Cells in State Dependent Olfactory Responses. Trygve Bakken & Gunnar Poplawski
The Role of Mitral Cells in State Dependent Olfactory Responses Trygve akken & Gunnar Poplawski GGN 260 Neurodynamics Winter 2008 bstract Many behavioral studies have shown a reduced responsiveness to
More informationWhat do you notice? Edited from
What do you notice? Edited from https://www.youtube.com/watch?v=ffayobzdtc8&t=83s How can a one brain region increase the likelihood of eliciting a spike in another brain region? Communication through
More informationCurrent Literature In Clinical Science. Psychopathology and Seizure Threshold
Current Literature In Clinical Science Psychopathology and Seizure Threshold Epilepsy, Suicidality, and Psychiatric Disorders: A Bidirectional Association Hesdorffer DC, Ishihara L, Mynepalli L, Webb DJ,
More informationResonant synchronization of heterogeneous inhibitory networks
Cerebellar oscillations: Anesthetized rats Transgenic animals Recurrent model Review of literature: γ Network resonance Life simulations Resonance frequency Conclusion Resonant synchronization of heterogeneous
More informationTNS Journal Club: Interneurons of the Hippocampus, Freund and Buzsaki
TNS Journal Club: Interneurons of the Hippocampus, Freund and Buzsaki Rich Turner (turner@gatsby.ucl.ac.uk) Gatsby Unit, 22/04/2005 Rich T. Introduction Interneuron def = GABAergic non-principal cell Usually
More informationSynaptic excitation of principal cells in the cat's lateral geniculate nucleus during focal epileptic seizures in the visual cortex
Synaptic excitation of principal cells in the cat's lateral geniculate nucleus during focal epileptic seizures in the visual cortex Andrzej wr6be11, Anders ~ edstr~m~ and Sivert ~indstrsm~ 'Department
More informationBasic Science of Representative Normal Human EEG Potentials
Basic Science of Representative Normal Human EEG Potentials Seyed M Mirsattari, MD, PhD, FRCPC Departments of Clinical Neurological Sciences, Medical Biophysics, Diagnostic Imaging, Psychology University
More informationSleep-Wake Cycle I Brain Rhythms. Reading: BCP Chapter 19
Sleep-Wake Cycle I Brain Rhythms Reading: BCP Chapter 19 Brain Rhythms and Sleep Earth has a rhythmic environment. For example, day and night cycle back and forth, tides ebb and flow and temperature varies
More information