title: Synaptic and non-synaptic mechanisms of amygdala recruitment into temporolimbic epileptiform activities.
abstract: Lateral amygdala (LA) activity during synchronized-epileptiform discharges in temporolimbic circuits was investigated in rat horizontal slices containing the amygdala, hippocampus (Hip), perirhinal (Prh) and lateral entorhinal (LEnt) cortex, through multiple-site extra- and intracellular recording techniques and measurement of the extracellular K+ concentration. Application of 4-aminopyridine (50 microm) induced epileptiform discharges in all regions under study. Slow interictal-like burst discharges persisted in the Prh/LEnt/LA after disconnection of the Hip, seemed to originate in the Prh as shown from time delay analyses, and often preceded the onset of ictal-like activity. Disconnection of the amygdala resulted in de-synchronization of epileptiform discharges in the LA from those in the Prh/LEnt. Interictal-like activity was intracellularly reflected in LA projection neurons as gamma-aminobutyric acid (GABA)A/B receptor-mediated synaptic responses, and depolarizing electrogenic events (spikelets) residing on the initial phase of the GABA response. Spikelets were considered antidromically conducted ectopic action potentials generated at axon terminals, as they were graded in amplitude, were not abolished through hyperpolarizing membrane responses (which effectively blocked evoked orthodromic action potentials), lacked a clear prepotential or synaptic potential, were not affected through blockers of gap junctions, and were blocked through remote application of tetrodotoxin at putative target areas of LA projection neurons. Remote application of a GABAB receptor antagonist facilitated spikelet generation. A transient elevation in the extracellular K+ level averaging 3 mm above baseline occurred in conjunction with interictal-like activity in all areas under study. We conclude that interictal-like discharges in the LA/LEnt/Prh spread in a predictable manner through the synaptic network with the Prh playing a leading role. The rise in extracellular K+ may provide a depolarizing mechanism for recruitment of interneurons and generation of ectopic action potentials at axon terminals of LA projection neurons. Antidromically conducted ectopic action potentials may provide a spreading mechanism of seizure activity mediated by diffuse axonal projections of LA neurons.
authors.affiliation: Institut für Physiologie, Medizinische Fakultät, Otto-von-Guericke-Universität Magdeburg, D-39120 Magdeburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Klueva
authors.forename: Thomas
authors.initials: T
authors.lastname: Munsch
authors.forename: Doris
authors.initials: D
authors.lastname: Albrecht
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
mesh_terms: D015761:4-Aminopyridine; D000200:Action Potentials; D000679:Amygdala / Q000166:cytology / Q000502:physiology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002229:Carbenoxolone / Q000494:pharmacology; D004210:Dissection; D004558:Electric Stimulation; D018728:Entorhinal Cortex / Q000502:physiology; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects; D005110:Extracellular Space; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010721:Phosphinic Acids / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D000897:Anti-Ulcer Agents; D018756:GABA Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; C085075:CGP 55845A; D013779:Tetrodotoxin; D015761:4-Aminopyridine; D002229:Carbenoxolone; D011188:Potassium; D001640:Bicuculline