GABA-mediated synchronization in the human neocortex: elevations in extracellular potassium and presynaptic mechanisms.
Field potential and extracellular [K(+)] ([K(+)](o)) recordings were made in the human neocortex in an in vitro slice preparation to study the synchronous activity that occurs in the presence of 4-aminopyridine (50 microM) and ionotropic excitatory amino acid receptor antagonists. Under these experimental conditions, negative or negative-positive field potentials accompanied by rises in [K(+)](o) (up to 4.1 mM from a baseline of 3.25 mM) occurred spontaneously at intervals of 3-27 s. Both field potentials and [K(+)](o) elevations were largest at approximately 1000 microm from the pia. Similar events were induced by neocortical electrical stimuli. Application of medium containing low [Ca(2+)]/high [Mg(2+)] (n=3 slices), antagonism of the GABA(A) receptor (n=7) or mu-opioid receptor activation (n=4) abolished these events. Hence, they represented network, GABA-mediated potentials mainly reflecting the activation of type A receptors following GABA release from interneurons. The GABA(B) receptor agonist baclofen (10-100 microM, n=11) reduced and abolished the GABA-mediated potentials (ID(50)=18 microM). Baclofen effects were antagonized by the GABA(B) receptor antagonist CGP 35348 (0.1-1 mM, n=6; ID(50)=0.19 mM). CGP 38345 application to control medium increased the amplitude of the GABA-mediated potentials and the concomitant [K(+)](o) rises without modifying their rate of occurrence. The GABA-mediated potentials were not influenced by the broad-spectrum metabotropic glutamate agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (100 microM, n=10), but decreased in rate with the group I receptor agonist (S)-3,5-dihydroxyphenylglycine (10-100 microM, n=9). Our data indicate that human neocortical networks challenged with 4-aminopyridine generate glutamatergic-independent, GABA-mediated potentials that are modulated by mu-opioid and GABA(B) receptors presumably located on interneuron terminals. These events are associated with [K(+)](o) elevations that may contribute to interneuron synchronization in the absence of ionotropic excitatory synaptic transmission.
Louvel
J
J
Montreal Neurological Institute and Department of Neurology, McGill University, Montreal, QC, Canada.
Papatheodoropoulos
C
C
Siniscalchi
A
A
Kurcewicz
I
I
Pumain
R
R
Devaux
B
B
Turak
B
B
Esposito
V
V
Villemeure
J G
JG
Avoli
M
M
D015761:4-Aminopyridine / Q000494:pharmacology; D000328:Adult; D003344:Cortical Synchronization; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D019579:Neocortex / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D017729:Presynaptic Terminals / Q000502:physiology; D018079:Receptors, GABA / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018079:Receptors, GABA; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; D005680:gamma-Aminobutyric Acid; D015761:4-Aminopyridine; D011188:Potassium