The Spatiotemporal Dynamics of Phase Synchronization during Epileptogenesis in Amygdala-Kindling Mice

The synchronization among the activities of neural populations in functional regions is one of the most important electrophysiological phenomena in epileptic brains. The spatiotemporal dynamics of phase synchronization was investigated to reveal the reciprocal interaction between different functional regions during epileptogenesis. Local field potentials (LFPs) were recorded simultaneously from the basolateral amygdala (BLA), the cornu ammonis 1 of hippocampus (CA1) and the mediodorsal nucleus of thalamus (MDT) in the mouse amygdala-kindling models during the development of epileptic seizures. The synchronization of LFPs was quantified between BLA, CA1 and MDT using phase-locking value (PLV). During amygdala kindling, behavioral changes (from stage 0 to stage 5) of mice were accompanied by after-discharges (ADs) of similar waveforms appearing almost simultaneously in CA1, MDT, as well as BLA. AD durations were positively related to the intensity of seizures. During seizures at stages 1~2, PLVs remained relatively low and increased dramatically shortly after the termination of the seizures; by contrast, for stages 3~5, PLVs remained a relatively low level during the initial period but increased dramatically before the seizure termination. And in the theta band, the degree of PLV enhancement was positively associated with seizure intensity. The results suggested that during epileptogenesis, the functional regions were kept desynchronized rather than hyper-synchronized during either the initial or the entire period of the seizures; so different dynamic patterns of phase synchronization may be involved in different periods of the epileptogenesis, and this might also reflect that during seizures at different stages, the mechanisms underlying the dynamics of phase synchronization were different.

[1]  R. Racine,et al.  Modification of seizure activity by electrical stimulation. 3. Mechanisms. , 1972, Electroencephalography and clinical neurophysiology.

[2]  J. Burchfiel,et al.  Stepwise progression of kindling: Perspectives from the kindling antagonism model , 1989, Neuroscience & Biobehavioral Reviews.

[3]  Hai-Qing Gong,et al.  Involvement of Thalamus in Initiation of Epileptic Seizures Induced by Pilocarpine in Mice , 2014, Neural plasticity.

[4]  E. Bertram,et al.  The Relevance of Kindling for Human Epilepsy , 2007, Epilepsia.

[5]  M M Mesulam,et al.  Large‐scale neurocognitive networks and distributed processing for attention, language, and memory , 1990, Annals of neurology.

[6]  J. Régis,et al.  The role of corticothalamic coupling in human temporal lobe epilepsy. , 2006, Brain : a journal of neurology.

[7]  Kaspar Anton Schindler,et al.  Assessing seizure dynamics by analysing the correlation structure of multichannel intracranial EEG. , 2006, Brain : a journal of neurology.

[8]  P. Mangan,et al.  The Midline Thalamus: Alterations and a Potential Role in Limbic Epilepsy , 2001, Epilepsia.

[9]  F. Varela,et al.  Measuring phase synchrony in brain signals , 1999, Human brain mapping.

[10]  Guifen Chen,et al.  Large-scale neural ensemble recording in the brains of freely behaving mice , 2006, Journal of Neuroscience Methods.

[11]  Yitzhak Schiller,et al.  Network Dynamics during Development of Pharmacologically Induced Epileptic Seizures in Rats In Vivo , 2010, The Journal of Neuroscience.

[12]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[13]  Kaspar Anton Schindler,et al.  Synchronization and desynchronization in epilepsy: controversies and hypotheses , 2012, The Journal of physiology.

[14]  Janet Wiles,et al.  Action Potential Waveform Variability Limits Multi-Unit Separation in Freely Behaving Rats , 2012, PloS one.

[15]  Xin-Wei Gong,et al.  Effective Connectivity of Hippocampal Neural Network and Its Alteration in Mg2+-Free Epilepsy Model , 2014, PloS one.

[16]  Wolfgang Löscher,et al.  Animal Models of Limbic Epilepsies: What Can They Tell Us? , 2002, Brain pathology.

[17]  E. Halgren,et al.  Single-neuron dynamics in human focal epilepsy , 2011, Nature Neuroscience.

[18]  R. Racine,et al.  Kindling: basic mechanisms and clinical validity. , 1990, Electroencephalography and clinical neurophysiology.

[19]  J. Gotman,et al.  Patterns of altered functional connectivity in mesial temporal lobe epilepsy , 2012, Epilepsia.

[20]  E. Bertram,et al.  Midline Thalamic Region: Widespread Excitatory Input to the Entorhinal Cortex and Amygdala , 2002, The Journal of Neuroscience.

[21]  J. Palva,et al.  Phase Synchrony among Neuronal Oscillations in the Human Cortex , 2005, The Journal of Neuroscience.

[22]  E. Bertram,et al.  Multiple roles of midline dorsal thalamic nuclei in induction and spread of limbic seizures , 2008, Epilepsia.

[23]  O. Muzik,et al.  Metabolic Changes of Subcortical Structures in Intractable Focal Epilepsy , 2004, Epilepsia.

[24]  D. Mcintyre,et al.  Kindling: some old and some new , 2002, Epilepsy Research.

[25]  Hal Blumenfeld,et al.  Neocortical and Thalamic Spread of Amygdala Kindled Seizures , 2007, Epilepsia.

[26]  D. Margineanu,et al.  Inhibition of neuronal hypersynchrony in vitro differentiates levetiracetam from classical antiepileptic drugs. , 2000, Pharmacological research.

[27]  E. Bertram,et al.  Excitatory amplification through divergent–convergent circuits: The role of the midline thalamus in limbic seizures , 2011, Neurobiology of Disease.

[28]  R. Racine,et al.  Modification of seizure activity by electrical stimulation. II. Motor seizure. , 1972, Electroencephalography and clinical neurophysiology.

[29]  F. Mormann,et al.  Mean phase coherence as a measure for phase synchronization and its application to the EEG of epilepsy patients , 2000 .

[30]  William Gaetz,et al.  Enhanced Synchrony in Epileptiform Activity? Local versus Distant Phase Synchronization in Generalized Seizures , 2005, The Journal of Neuroscience.

[31]  Linda Douw,et al.  Epilepsy is related to theta band brain connectivity and network topology in brain tumor patients , 2010, BMC Neuroscience.

[32]  G. Buzsáki Theta Oscillations in the Hippocampus , 2002, Neuron.

[33]  P. Somogyi,et al.  Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo , 2003, Nature.

[34]  Kaspar Anton Schindler,et al.  Increasing synchronization may promote seizure termination: Evidence from status epilepticus , 2007, Clinical Neurophysiology.

[35]  Nadia Colombo,et al.  Temporal lobe epilepsy: neuropathological and clinical correlations in 243 surgically treated patients. , 2009, Epileptic disorders : international epilepsy journal with videotape.

[36]  J. Martinerie,et al.  The brainweb: Phase synchronization and large-scale integration , 2001, Nature Reviews Neuroscience.

[37]  Mark R. Bower,et al.  Synchrony in normal and focal epileptic brain: the seizure onset zone is functionally disconnected. , 2010, Journal of neurophysiology.

[38]  David Nicholls,et al.  Synchrony Dynamics Across Brain Structures in Limbic Epilepsy Vary Between Initiation and Termination Phases of Seizures , 2013, IEEE Transactions on Biomedical Engineering.

[39]  J. Martinerie,et al.  Comparison of Hilbert transform and wavelet methods for the analysis of neuronal synchrony , 2001, Journal of Neuroscience Methods.

[40]  Tomoki Fukai,et al.  Accurate spike sorting for multi‐unit recordings , 2010, The European journal of neuroscience.

[41]  Margaret Fahnestock,et al.  Kindling and status epilepticus models of epilepsy: rewiring the brain , 2004, Progress in Neurobiology.

[42]  J. Gotman,et al.  Antiepileptic drugs abolish ictal but not interictal epileptiform discharges in vitro , 2010, Epilepsia.

[43]  M. Bentivoglio,et al.  Thalamic midline cell populations projecting to the nucleus accumbens, amygdala, and hippocampus in the rat , 1990, The Journal of comparative neurology.

[44]  Rodrigo Quian Quiroga,et al.  Past, present and future of spike sorting techniques , 2015, Brain Research Bulletin.

[45]  Kaushik Majumdar,et al.  Synchronization Implies Seizure or Seizure Implies Synchronization? , 2013, Brain Topography.

[46]  José Luis Pérez Velazquez,et al.  On the Spatial Organization of epileptiform Activity , 2008, Int. J. Bifurc. Chaos.

[47]  L. Mei,et al.  Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons , 2011, Nature Neuroscience.

[48]  R. Miles,et al.  Contributions of intrinsic and synaptic activities to the generation of neuronal discharges in in vitro hippocampus , 2000, The Journal of physiology.

[49]  M. Avoli,et al.  Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro , 2002, Progress in Neurobiology.

[50]  R. Goodman,et al.  Cortical abnormalities in epilepsy revealed by local EEG synchrony , 2007, NeuroImage.

[51]  Y. Guo,et al.  Low-frequency stimulation inhibits epileptogenesis by modulating the early network of the limbic system as evaluated in amygdala kindling model , 2013, Brain Structure and Function.

[52]  P. L. Parmeggiani,et al.  On the functional significance of the circuit of Papez. , 1971, Brain research.