Laminar properties of 4-aminopyridine-induced synchronous network activities in rat neocortex.
We examined the effects of 4-aminopyridine (4-AP) on isolated horizontal (superficial, middle and deep) rat neocortical slices in order to study laminar synchronous network behavior directly. Application of 4-AP induced spontaneous synchronized activity in all of these types of slices. In middle and deep layer slices the activities were similar to those of coronal slices, consisting of periodic short- and long-duration discharges. In superficial slices distinct spontaneous rhythmic multiphasic burst discharges were induced. Ionotropic glutamate receptor antagonists blocked the 4-AP-induced synchronous activities in middle and deep layer slices, but those in superficial slices persisted. The GABA(A) receptor antagonist picrotoxin suppressed this spontaneous synchronous activity resistant to 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (a NMDA receptor antagonist) and 6-cyano-7-nitroquinoxaline-2,3-dione (a non-NMDA receptor antagonist), in superficial slices, leaving small, slow spontaneous events. In superficial slices with intact excitatory amino acid transmission, picrotoxin attenuated the 4-AP-induced spontaneous synchronous discharges, even in this highly convulsant environment. By contrast, conventional coronal slices showed robust spontaneous epileptiform discharges under these circumstances. In intact coronal slices focal 4-AP application in superficial layers induced spontaneous inhibitory GABAergic events, while delivery into deep layers led to epileptiform discharges. From these results we conclude that: (1) 4-AP-induced population discharges are driven by glutamatergic transmission in middle and deep layer horizontal slices, and by GABAergic transmission in superficial layers; (2) only superficial layers are capable of supporting synchronized GABAergic activity independent of excitatory amino acid transmission; (3) superficial layers do not sustain epileptiform activity in the absence of deep layer neurons; and (4) synchronized superficial networks can inhibit deep layer neuronal activity.
Yang
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Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Box 29, Brooklyn 11203, USA.
Benardo
L S
LS
D015761:4-Aminopyridine / Q000494:pharmacology*; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000502:physiology; D019579:Neocortex / Q000187:drug effects* / Q000502:physiology*; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D015761:4-Aminopyridine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010852:Picrotoxin; D010879:Piperazines; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid