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penicillin epilepsy (FGPE) are very similar to the spike-and-wave discharges of a human absence seizure. The use of rats has also been a common method for studying the spike-and-wave phenomenon. The
Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and the inbred Wistar Albino Glaxo rats from Rijswijk (WAG/Rij) are the two main strains of rats that have been used in studies. The rats from these two strains show spontaneously occurring absence seizures that consist of typical spike-and-wave activity seen on an EEG. Rat genetic models have given data showing that the expression of absence seizures involves both the thalamic and cortical networks. In both models, electrophysiological data showed that spike-and-waves are initiated in the somatosensory cortex and then spread rapidly to the motor cortex and thalamic nuclei. Using in vivo intracellular recordings, it was found in the GAERS that spike-and-wave are initiated in layer 5/6 neurons of the somatosensory cortex. These neurons, show a distinctive hyperactivity associated with a membrane depolarization. They are suggested to lead the firing of distant cortical cells during the epileptic discharge.
78:, recorded the first EEG of an absence seizure in the 1920s, which led the way for the general notion of spike-and-wave electrophysiology. His first recording of a human EEG was made in 1924 using a galvanometer, but his results were very crude and showed small, undefined oscillations. He continued to refine his technique and increase the sensitivity to the galvanometer, in which he accumulated many EEGs of individuals with and without a brain malfunction or disorder. Among those tested were patients with epilepsy, dementia, and brain tumors. Hans Berger published his findings in 1933, however his results did not give a definitive characterization of the general EEG pattern seen during an epileptic seizure. In 1935, F.A. Gibbs, H. Davis, and W.G. Lennox provided a clear description of EEG spike-and-wave patterns during a petit mal epileptic seizure. An intracellular recording performed by DA Pollen in 1964 revealed that the "spike" aspect of the phenomenon was associated with neuronal firing and the "wave" aspect was associated with hyperpolarization.
263:. Absence seizures are generalized epileptic seizures that can be divided into two types, typical and atypical. Typical and atypical absence seizures display two different kinds of spike-and-wave patterns. Typical absence seizures are described by generalized spike-and-wave patterns on an EEG with a discharge of 2.5 Hz or greater. They can be characterized by an increase in synchronization of discharges in the thalamocortical circuitry. They can also be characterized by the acute onset and termination of the seizure. Atypical absence seizures have a higher frequency in children with severe epilepsy that suffer from multiple types of seizures. The spike-and-wave pattern seen here is more irregular than the generalized pattern and also seems to be slower. This irregular pattern is due to non-synchronous discharges of the thalamocortical circuitry. The onset and termination in these atypical absence seizures seem to be less acute than the typical absence seizures.
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and juxtacellularly labeled. Medium oscillations (5–9 Hz) in both types of rats were noted to occur randomly in an unsynchronized pattern in relay and reticular neurons. However, spontaneous spike-and-wave discharges were observed in epileptic rats when the medium oscillations became synchronized, suggesting a dependence of the two. However, since medium ranged oscillations only developed into spike-and-wave discharges spontaneously, genetic factors also seem to contribute to the initiation of synchronized oscillations. These genetic factors may contribute to spike-and-wave oscillations by decreasing the action potential threshold in reticular cells, making them more excitable and potentially easier to initiate synchronized firing. Another study has shown that these medium oscillations have led to spike-and-wave discharges. The activity of the primary and secondary cortical regions, as well as the adjacent
275:(LGS) is a childhood epileptic encephalopathy characterized with generalized seizures and slow spike-wave activity while awake. LGS is a combination of atonic absences, tonic seizures, cognitive deterioration, and slow spike-wave activity in the EEG. This syndrome usually results from focal, multifocal, or diffuse brain damage and can be divided into symptomatic and cryptogenic types. Cognitive deterioration with high-frequency spike-wave activity affects most patients 2–9 years old with generalized seizures. The age of onset for LGS is between 1 and 10 years, between 2 and 6 years for symptomatic cases and 5 and 8 years for cryptogenic cases. Episodes can be triggered by modifications of treatment, which usually involves benzodiazepines, or changes in the conditions of life.
171:) in the thalamocortical network have also shown to display some role in the generation of spike-and-wave discharges (SWDs) associated with absence epilepsy. The different subtypes of mGlu receptors have a modulatory role on either excitatory or inhibitory synaptic transmission. There are conflicting hypotheses for the function of the many mGlu receptors with regards to epileptic seizures, however the role of the mGlu4 receptor is undisputed in the generation of SWDs, shown in animal models. In one study, knockout mice lacking mGlu4 receptors showed a disruption of glutamate and GABA release in the thalamocortical network and were resistant to absence seizures induced by low doses of
286:(OS), also known as early infantile epileptic encephalopathy (EIEE) with suppression-burst (S-B), is the most severe and the earliest-developing epileptic encephalopathy in children. This syndrome is characterized on an EEG by high voltage bursts and slow waves mixed with multifocal spikes alternating with almost flat suppression phases. The S-B will gradually begin to taper away at 3 months and disappear by 6 months. OS will transition to West syndrome or LGS with age. Tonic spasms are the main seizures observed in OS. Unlike LGS, the spike-and-wave pattern is consistent during both waking and sleeping states. Symptoms of OS include:
390:, and the new anti-epileptic drugs. Over the past 20 years, 15 new anti-epileptic drugs with positive outcomes have been introduced to the public. These new AEDs are aimed at improving the cost-benefit balance in AED therapy, improving tolerability profiles and reducing potential for drug interaction. Despite these major advances, there is always room for improvement, especially regarding the tailored treatment of individuals who have suffered adverse effects from older AEDs.
66:(AEDs) are commonly prescribed to treat epileptic seizures, and new ones are being discovered with fewer adverse effects. Today, most of the research is focused on the origin of the generalized bilateral spike-and-wave discharge. One proposal suggests that a thalamocortical (TC) loop is involved in the initiation spike-and-wave oscillations. Although there are several theories, the use of animal models has provided new insight on spike-and-wave discharge in humans.
179:) of normal mice protected against pentylenetetrazole induced seizures. Also, WAG/Rij rats show an increased expression of mGlu4 receptors in the nRT when compared to a control group of normal rats. These studies show that an increase in the expression and/or activity of mGlu4 receptors is associated with spike-and-wave discharges seen in absence seizures. This link between mGlur4 receptors and SWDs has led to the search for a selective mGlu4 receptor
87:
367:(AEDs) is very prevalent. AEDs aim to slow down the excess firing, associated with spike-and-wave discharges, at the beginning of seizures. They can bring about serious adverse drug reactions so physicians need to be aware of the safety and admissibility for each drug. These adverse effects are a major source of disability, morbidity, and mortality. Some of the adverse effects, such as serious cutaneous,
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135:, contribute to the repolarization and hyperpolarization of the membrane. In an epileptic seizure, there are periods of a sustained depolarization, which cause a train of action potentials followed by a repolarization and hyperpolarization phase. The train of action potentials constitutes the “spike” phase, and the repolarization and hyperpolarization constitute the “wave” phase.
355:. This continuous pattern during sleep, like other aspects of spike-and-wave activity, are not completely understood either. However, what is hypothesized is that corticothalamic neuronal network that is involved in oscillating sleep patterns may begin to function as a pathologic discharging source.
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to lower blood glucose levels by 40%. This reduction in blood glucose led to double the occurrence of spike-and-wave activity. Similar to the insulin effect, overnight fasting, where blood glucose levels were reduced by 35% also showed this double in occurrence. This model concludes that low glucose
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Another possible initiation pattern tested in rats suggested the thalamocortical (TC) loop is involved in the initiation of spike-and-wave oscillations under certain conditions. In this study, relay and reticular thalamic neurons of epileptic and non-epileptic rats were dual extracellularly recorded
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The use of animal models, such as cats, for studying spike-and-wave discharges, has provided useful data for studying epilepsy in humans. One method of inducing a seizure in a cat is to inject penicillin into the cortical region of the brain. The spike-and-wave discharges seen in feline generalized
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Another study revealed that glucose may also be relevant to spike-and-wave occurrence in mice that contained a knock-in of the human GABA(A) γ2(R43Q) mutation, which has been known to be a genetic factor involved in the causation of absence epilepsy. These absence seizure prone mice were injected
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Although there is evidence for the generation of a large EPSP, many studies have shown that synaptic inhibition remains functional during the generation of these types of paroxysmal depolarizing shifts. Also, it has been shown that a decrease in the inhibitory activity does not affect neocortical
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was introduced as the first anti-epileptic drug 150 years ago. Because of the adverse effects mentioned above, bromide is not currently in use as an AED. Early treatment discontinuation was occurring far too frequently and eventually resulted in negative effects on several patients. Current
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Ngomba, R.T; Ferraguti, F; Badura, A; Citraro, R; Santolini, I; Battaglia, G; Bruno, V; De Sarro, G; Simonyi, A; Van
Luijtelaar, G; Nicoletti, F (2008). "Positive allosteric modulation of metabotropic glutamate 4 (mGlu4) receptors enhances spontaneous and evoked absence seizures".
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gene may interfere with elongo-mediated gene interaction, specifically during the developmental stages of the cortical region. This mutation may be responsible for a predisposition to spike-and-wave discharges, as well as other neurodevelopmental disorders.
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Pinault, D; Vergnes, M; Marescaux, C (2001). "Medium-voltage 5–9-Hz oscillations give rise to spike-and-wave discharges in a genetic model of absence epilepsy: In vivo dual extracellular recording of thalamic relay and reticular neurons".
351:(ESES) and found in 0.2–0.5% of all child epilepsy cases. Discharges rarely result in absence seizures, but motor impairment and neurophysiological regression have been found in CSWS. Spike-and-wave activity occupies about 85% of the
54:. Many aspects of the pattern are still being researched and discovered, and still many aspects are uncertain. The spike-and-wave pattern is most commonly researched in absence epilepsy, but is common in several epilepsies such as
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leads to an increase in the intracellular chloride concentration, which in non-epileptic situations would lead to an IPSP. However, in seizure-related depolarizing shifts, there is a substantial activation of postsynaptic
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were recorded using an EEG and where applied with electrical stimulation. The findings here showed that the onset of spike-and-wave discharged were followed by 5–9 Hz oscillations in these cortical regions as well.
143:) is not accepted as a general mechanism for epileptic activity. Many studies have shown that the inhibitory postsynaptic signaling is actually increased during these epileptic attacks. The activation of postsynaptic
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also have some effect on the depolarization of the cell, but the effect is minimal compared to the sodium channels. However, the increasing concentration of intracellular calcium leads to greater activation of
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Velazquez, Jose L. Perez; Huo, Jeanne Zhen; Dominguez, L. Garcia; Leshchenko, Yevgen; Snead Iii, O. Carter (2007). "Typical versus
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347:(CSWS), a rare form of age-related epilepsy, children between the ages of three and seven exhibit continuous spike-and-wave discharges during slow-sleep. This rare disorder is also called
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Veggiotti, P; Pera, M. C; Teutonico, F; Brazzo, D; Balottin, U; Tassinari, C. A (2012). "Therapy of encephalopathy with status epilepticus during sleep (ESES/CSWS syndrome): An update".
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Timofeev, I; Grenier, F; Steriade, M (2002). "The role of chloride-dependent inhibition and the activity of fast-spiking neurons during cortical spike–wave electrographic seizures".
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Zheng, Thomas W; o'Brien, Terence J; Morris, Margaret J; Reid, Christopher A; Jovanovska, Valentina; o'Brien, Patrick; Van Raay, Leena; Gandrathi, Arun K; Pinault, Didier (2012).
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106:, along the thalamocortical network. The EEG “spike” of the spike-and-wave complex corresponds to the depolarization of the neuronal membrane potential, also called a
271:
Epileptic encephalopathies are a group of conditions that result in deterioration of sensory, cognitive, and motor functions due to consistent epileptic activity.
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receptors, which leads to an even larger concentration of intracellular chloride concentration. This change in ion concentration gradient causes the GABA
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114:) in the absence of synaptic inhibition, which relayed the action potentials in the neurons by triggering activation of voltage-gated channels. The
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History of generalized epilepsy with absence seizures are dated to the eighteenth century, however the inventor of the electroencephalogram (EEG),
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Cohen, I; Navarro, V; Clemenceau, S; Baulac, M; Miles, R (2002). "On the Origin of
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1165:"Rhythmic neuronal activity in S2 somatosensory and insular cortices contribute to the initiation of absence-related spike-and-wave discharges"
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Szaflarski, Jerzy P; Difrancesco, Mark; Hirschauer, Thomas; Banks, Christi; Privitera, Michael D; Gotman, Jean; Holland, Scott K (2010).
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The spike-and-wave pattern seen during an absence seizure is the result of a bilateral synchronous firing of neurons ranging from the
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kindling. Therefore, the theory that spike-and-wave activity is caused by a giant EPSP due to the decrease or the absence of IPSPs (
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Meeren, Hanneke K. M; Pijn, Jan Pieter M; Van
Luijtelaar, Egidius L. J. M; Coenen, Anton M. L; Lopes Da Silva, Fernando H (2002).
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872:"Metabotropic glutamate receptors in the thalamocortical network: Strategic targets for the treatment of absence epilepsy"
164:, leading to an efflux of the chloride ions. This leads to a decreased amplitude or even reversed polarity of the IPSPs.
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39:, also known as ‘petit mal’ epilepsy. The basic mechanisms underlying these patterns are complex and involve part of the
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1111:"Deep Layer Somatosensory Cortical Neurons Initiate Spike-and-Wave Discharges in a Genetic Model of Absence Seizures"
919:"Modulation of Absence Seizures by the GABAAReceptor: A Critical Role for Metabotropic Glutamate Receptor 4 (mGluR4)"
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and hepatic events, usually require withdrawal in children and place a heavy burden on the costs of healthcare.
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levels could be a potential trigger for absence seizures, and could be an environmental risk factor for humans.
110:(PDS). The initial understanding behind the mechanism of the PDS was that it was caused by a very large EPSP (
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Pollen, D. A (1964). "Intracellular
Studies of Cortical Neurons During Thalamic Induced Wave and Spike".
35:. A spike-and-wave discharge is a regular, symmetrical, generalized EEG pattern seen particularly during
1057:"Cortical Focus Drives Widespread Corticothalamic Networks during Spontaneous Absence Seizures in Rats"
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EEG recording of generalized 3 Hz spike-and-wave discharges seen in a child during an absence seizure
828:"Disruption of Inhibition in Area CA1 of the Hippocampus in a Rat Model of Temporal Lobe Epilepsy"
183:(which will block these receptors) as a potential new drug for the treatment of absence epilepsy.
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Denslow, Maria J; Eid, Tore; Du, Fu; Schwarcz, Robert; Lothman, Eric W; Steward, Oswald (2001).
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Bursts of generalized spike-and-wave discharges lasting two seconds or longer is considered an
175:. Another study showed that bilateral injection of a mGlu4 receptor antagonist into the nRT (
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213:) has been identified as a key component in the transcription of genes known to regulate the
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A drawing of the human brain showing the thalamus and cortex relative to other structures.
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Reoccurrence after a solitary unprovoked seizure in children is about 50%, so the use of
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1298:"Cortical and subcortical contributions to absence seizure onset examined with EEG/fMRI"
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The first spike-and-wave pattern was recorded in the early twentieth century by
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232:. Hypotheses have been made that a mutation in the non-coding region of the
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224:and migration of neurons. Research on
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686:Drug Discovery Today: Disease Models
552:Perspectives in Biology and Medicine
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129:calcium-activated potassium channels
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339:Spike-and-wave pattern during sleep
328:Frequent minor generalized seizures
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345:continuous spike-and-wave syndrome
167:Metabotropic glutamate receptors (
160:inhibitory current to surpass the
141:inhibitory postsynaptic potentials
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133:voltage-gated potassium channels
31:(EEG) typically observed during
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521:10.1016/S0306-4522(01)00182-8
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209:Elongator Protein Complex 4 (
205:Genetic/developmental factors
116:voltage-gated sodium channels
108:paroxysmal depolarizing shift
1221:10.1097/WNP.0b013e31821213eb
1026:10.1016/0006-8993(87)90990-5
656:10.1016/0013-4694(64)90163-4
353:non-rapid eye movement sleep
334:Severe psychomotor prognosis
301:Inborn errors of metabolism
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1061:The Journal of Neuroscience
923:The Journal of Neuroscience
698:10.1016/j.ddmod.2008.07.005
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832:Journal of Neurophysiology
378:treatment options include
250:Spike-and-wave in epilepsy
177:thalamic reticular nucleus
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845:10.1152/jn.2001.86.5.2231
317:Posterior fossa anomalies
1302:Epilepsy & Behavior
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751:10.1126/science.1076510
593:Avoli, Massimo (2012).
309:Cortical malformations
273:Lennox-Gastaut syndrome
267:Lennox-Gastaut syndrome
56:Lennox-Gastaut syndrome
45:thalamocortical network
1690:Electroencephalography
304:Glycine encephalopathy
293:Mitochondrial disease
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1469:Brain and Development
564:10.1353/pbm.2001.0070
472:10.1002/ana.410370204
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915:Snead III, O. Carter
456:Snead III, O. Carter
365:anti-epileptic drugs
323:of mammillary bodies
29:electroencephalogram
27:is a pattern of the
1512:Epileptic Disorders
743:2002Sci...298.1418C
460:Annals of Neurology
64:Antiepileptic drugs
359:Clinical relevance
313:Cerebral asymmetry
187:Initiation factors
173:pentylenetetrazole
162:reversal potential
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33:epileptic seizures
22:
1670:978-0-12-088554-1
1426:Epilepsy Research
971:Neuropharmacology
737:(5597): 1418–21.
411:Epilepsy Research
284:Ohtahara syndrome
279:Ohtahara syndrome
60:Ohtahara syndrome
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541:
540:
503:
492:
491:
452:
443:
442:
406:
255:Absence epilepsy
120:action potential
37:absence epilepsy
1705:
1704:
1700:
1699:
1698:
1696:
1695:
1694:
1680:
1679:
1678:
1671:
1657:
1653:
1603:
1597:
1593:
1554:
1547:
1508:
1504:
1465:
1461:
1422:
1418:
1379:
1375:
1343:
1339:
1294:
1290:
1251:
1244:
1205:
1198:
1175:(11): 1948–58.
1161:
1154:
1107:
1100:
1053:
1049:
1010:
1006:
966:
962:
929:(16): 6218–24.
912:
905:
868:
861:
824:
820:
781:
774:
727:
723:
678:
671:
640:
636:
591:
587:
548:
544:
504:
495:
453:
446:
417:(2–3): 185–93.
407:
400:
396:
361:
341:
290:Genetic defects
281:
269:
261:absence seizure
257:
252:
207:
189:
159:
155:
148:
100:cerebral cortex
84:
82:Pathophysiology
72:
41:cerebral cortex
12:
11:
5:
1703:
1693:
1692:
1677:
1676:
1669:
1651:
1591:
1564:(9): 792–802.
1545:
1502:
1459:
1416:
1373:
1354:(8): 1585–93.
1337:
1288:
1242:
1196:
1152:
1121:(24): 6590–9.
1098:
1067:(4): 1480–95.
1047:
1014:Brain Research
1004:
960:
903:
882:(7): 1211–22.
859:
838:(5): 2231–45.
818:
791:(4): 1115–32.
772:
721:
669:
650:(4): 398–404.
634:
585:
542:
515:(1): 181–201.
493:
444:
397:
395:
392:
369:haematological
360:
357:
340:
337:
336:
335:
332:
329:
326:
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318:
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299:
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280:
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268:
265:
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251:
248:
206:
203:
198:insular cortex
188:
185:
157:
153:
146:
83:
80:
71:
68:
25:Spike-and-wave
9:
6:
4:
3:
2:
1702:
1691:
1688:
1687:
1685:
1672:
1666:
1662:
1655:
1647:
1643:
1639:
1635:
1630:
1625:
1621:
1617:
1614:(7): 519–33.
1613:
1609:
1602:
1595:
1587:
1583:
1579:
1575:
1571:
1567:
1563:
1559:
1552:
1550:
1541:
1537:
1533:
1529:
1525:
1521:
1517:
1513:
1506:
1498:
1494:
1490:
1486:
1482:
1478:
1475:(6): 459–68.
1474:
1470:
1463:
1455:
1451:
1447:
1443:
1439:
1435:
1431:
1427:
1420:
1412:
1408:
1404:
1400:
1396:
1392:
1388:
1384:
1377:
1369:
1365:
1361:
1357:
1353:
1349:
1341:
1333:
1329:
1324:
1319:
1315:
1311:
1308:(4): 404–13.
1307:
1303:
1299:
1292:
1284:
1280:
1276:
1272:
1268:
1264:
1261:(1): 115–20.
1260:
1256:
1249:
1247:
1238:
1234:
1230:
1226:
1222:
1218:
1215:(2): 154–64.
1214:
1210:
1203:
1201:
1192:
1188:
1183:
1178:
1174:
1170:
1166:
1159:
1157:
1148:
1144:
1139:
1134:
1129:
1124:
1120:
1116:
1112:
1105:
1103:
1094:
1090:
1085:
1080:
1075:
1070:
1066:
1062:
1058:
1051:
1043:
1039:
1035:
1031:
1027:
1023:
1019:
1015:
1008:
1000:
996:
992:
988:
984:
980:
977:(2): 344–54.
976:
972:
964:
956:
952:
947:
942:
937:
932:
928:
924:
920:
916:
910:
908:
899:
895:
890:
885:
881:
877:
873:
866:
864:
855:
851:
846:
841:
837:
833:
829:
822:
814:
810:
806:
802:
798:
794:
790:
786:
779:
777:
768:
764:
760:
756:
752:
748:
744:
740:
736:
732:
725:
717:
713:
708:
703:
699:
695:
691:
687:
683:
676:
674:
665:
661:
657:
653:
649:
645:
638:
630:
626:
621:
616:
612:
608:
605:(5): 779–89.
604:
600:
596:
589:
581:
577:
573:
569:
565:
561:
558:(4): 522–42.
557:
553:
546:
538:
534:
530:
526:
522:
518:
514:
510:
502:
500:
498:
489:
485:
481:
477:
473:
469:
466:(2): 146–57.
465:
461:
457:
451:
449:
440:
436:
432:
428:
424:
420:
416:
412:
405:
403:
398:
391:
389:
385:
384:valproic acid
381:
376:
372:
370:
366:
356:
354:
350:
346:
333:
330:
327:
322:
319:
316:
314:
311:
310:
308:
303:
302:
300:
295:
294:
292:
289:
288:
287:
285:
276:
274:
264:
262:
247:
244:
238:
235:
231:
227:
223:
219:
216:
212:
202:
199:
193:
184:
182:
178:
174:
170:
165:
163:
150:
142:
136:
134:
130:
125:
121:
117:
113:
109:
105:
101:
98:(part of the
97:
88:
79:
77:
67:
65:
61:
57:
53:
48:
46:
42:
38:
34:
30:
26:
18:
1660:
1654:
1611:
1607:
1594:
1561:
1557:
1515:
1511:
1505:
1472:
1468:
1462:
1429:
1425:
1419:
1386:
1382:
1376:
1351:
1347:
1340:
1305:
1301:
1291:
1258:
1254:
1212:
1208:
1172:
1168:
1118:
1114:
1064:
1060:
1050:
1020:(1): 68–79.
1017:
1013:
1007:
974:
970:
963:
926:
922:
879:
875:
835:
831:
821:
788:
785:Neuroscience
784:
734:
730:
724:
692:(1): 45–57.
689:
685:
647:
643:
637:
602:
598:
588:
555:
551:
545:
512:
509:Neuroscience
508:
463:
459:
414:
410:
388:ethosuximide
373:
362:
348:
344:
342:
282:
270:
258:
239:
233:
225:
218:cytoskeleton
208:
194:
190:
166:
137:
93:
73:
49:
24:
23:
1629:2158/647763
1608:Drug Safety
1518:(1): 1–11.
76:Hans Berger
52:Hans Berger
1432:: S58–67.
394:References
181:antagonist
58:(LGS) and
1383:Epilepsia
1348:Epilepsia
1255:Epilepsia
1169:Epilepsia
876:Epilepsia
599:Epilepsia
380:phenytoin
230:phenotype
149:receptors
102:) to the
96:neocortex
1684:Category
1646:46638862
1638:22702637
1586:25540685
1578:22832500
1540:31107327
1532:22426353
1489:21967765
1454:38268884
1446:16829045
1403:11520318
1389:: 23–6.
1368:17484751
1332:20580319
1283:23856435
1275:21175610
1237:16679450
1229:21399511
1191:23083325
1147:17567820
1093:11850474
1042:24544393
999:25229534
991:18022649
955:10934271
898:21569017
854:11698514
805:12379264
767:28066491
759:12434059
716:19190736
664:14236822
629:22360294
580:30664678
572:11600799
537:34005173
529:11483311
488:21233781
431:20092980
321:Agenesis
222:motility
104:thalamus
1497:6304812
1411:6494524
1323:2922486
1138:6672429
1084:6757554
1034:3032351
946:6772607
813:4832421
739:Bibcode
731:Science
707:2633479
620:4878899
480:7847856
439:1284961
375:Bromide
243:insulin
220:, cell
122:. The
70:History
1667:
1644:
1636:
1584:
1576:
1538:
1530:
1495:
1487:
1452:
1444:
1409:
1401:
1366:
1330:
1320:
1281:
1273:
1235:
1227:
1189:
1145:
1135:
1091:
1081:
1040:
1032:
997:
989:
953:
943:
896:
852:
811:
803:
765:
757:
714:
704:
662:
627:
617:
578:
570:
535:
527:
486:
478:
437:
429:
169:mGluRs
43:, the
1642:S2CID
1604:(PDF)
1582:S2CID
1536:S2CID
1493:S2CID
1450:S2CID
1407:S2CID
1279:S2CID
1233:S2CID
1038:S2CID
995:S2CID
809:S2CID
763:S2CID
576:S2CID
533:S2CID
484:S2CID
435:S2CID
241:with
215:actin
1665:ISBN
1634:PMID
1574:PMID
1528:PMID
1485:PMID
1442:PMID
1399:PMID
1364:PMID
1328:PMID
1271:PMID
1225:PMID
1187:PMID
1143:PMID
1089:PMID
1030:PMID
987:PMID
951:PMID
894:PMID
850:PMID
801:PMID
755:PMID
712:PMID
660:PMID
625:PMID
568:PMID
525:PMID
476:PMID
427:PMID
234:ELP4
226:ELP4
211:ELP4
152:GABA
145:GABA
1624:hdl
1616:doi
1566:doi
1520:doi
1477:doi
1434:doi
1391:doi
1356:doi
1318:PMC
1310:doi
1263:doi
1217:doi
1177:doi
1133:PMC
1123:doi
1079:PMC
1069:doi
1022:doi
1018:405
979:doi
941:PMC
931:doi
884:doi
840:doi
793:doi
789:114
747:doi
735:298
702:PMC
694:doi
652:doi
615:PMC
607:doi
560:doi
517:doi
513:105
468:doi
419:doi
343:In
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