title: Emergence and propagation of interictal spikes in the subcortically denervated hippocampus.
abstract: Spontaneous and evoked field potentials and cellular discharges of the subcortically denervated dorsal hippocampus were studied by multisite recordings in the freely behaving rat. Characteristic short-duration (< 100 ms), large-amplitude (up to 10 mV) transients, termed interictal spikes (IIS), were seen after fimbria-fornix (FF) lesion. Both pyramidal cells and putative interneurons fired maximally during IIS, with some interneurons sustaining long bursts (up to 400 ms) of high-frequency discharges (400-600 Hz) after the IIS. The speed of propagation of IIS along the longitudinal axis of the hippocampus varied from 0.2 m/s to > 3 m/s. The majority of IIS (type 1) could be accounted for by an enhanced activity of the intrahippocampal associational systems; a second class of IIS (type 2) had positive polarities in the stratum radiatum of CA1 and CA3 and propagated very rapidly (> 1.5 m/s). The authors propose that type 2 IIS reflect somatic depolarization and discharge of pyramidal neurons due to nonsynaptic (probably ephaptic) effects. Ephaptic interactions may also explain the longitudinal propagation of IIS at speeds higher than the conduction velocities (0.5 m/s) of hippocampal fiber systems. IIS emerged during the first 3 weeks after fimbria-fornix lesion, their incidence reaching a plateau of 2/min thereafter. During the same time period, paired-pulse suppression increased in the dentate gyrus. The amplitude of test responses to angular bundle stimulation was potentiated by small-amplitude IIS but suppressed by large-amplitude IIS. The incidence of IIS was significantly suppressed during walking relative to standing still. Tetanic stimulation of the angular bundle or handling-induced stress resulted in a 10- to 20-fold increase in the incidence of IIS that lasted for about 30 minutes. There was a negative correlation between evoked field PSP slope and population spike amplitude in the dentate gyrus of FF-lesioned rats; this correlation was positive in intact rats. The authors attribute the above pathophysiological changes to sprouting of both excitatory and inhibitory GABAergic pathways as a result of denervation of the intrahippocampal circuitry. They hypothesize that the majority of the observed physiological alterations can be traced to a weakening of feedforward inhibition coupled with an enhancement of feedback inhibition and excitation.
authors.affiliation: Department of Neurosciences, University of California at San Diego, La Jolla 92093.
authors.forename: G
authors.initials: G
authors.lastname: Buzsáki
authors.forename: M
authors.initials: M
authors.lastname: Hsu
authors.forename: C
authors.initials: C
authors.lastname: Slamka
authors.forename: F H
authors.initials: FH
authors.lastname: Gage
authors.forename: Z
authors.initials: Z
authors.lastname: Horváth
mesh_terms: D000818:Animals; D003714:Denervation; D004558:Electric Stimulation; D004569:Electroencephalography; D004594:Electrophysiology; D004827:Epilepsy / Q000473:pathology / Q000503:physiopathology*; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D006234:Handling, Psychological; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D006651:Histocytochemistry; D009474:Neurons / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011999:Recruitment, Neurophysiological / Q000502:physiology