SYNAPTIC AND MEMBRANE MECHANISMS UNDERLYING SYNCHRONIZED OSCILLATIONSIN THE FERRET LATERAL GENICULATE-NUCLEUS IN-VITRO

1. The cellular basis for generation of spindle waves and a slower syn chronized oscillation resembling absence seizures was investigated wit h extracellular and intracellular recording techniques in slices of fe rret dorsal lateral geniculate nucleus (LGNd) maintained in vitro. 2. Intracellular recording from LGNd relay cells in vitro revealed that s pindle waves occurred once every 3-30 s and were associated with barra ges of inhibitory postsynaptic potentials (IPSPs) occurring at a frequ ency of 6-10 Hz. These IPSPs resulted in the generation of rebound low threshold Ca2+ spikes at 2-4 Hz, owing to the intrinsic propensity of LGNd relay cells to generate oscillatory burst firing in this frequen cy range. These rebound bursts of action potentials were highly synchr onized with local multiunit and single unit activity.3. The spindle wa ve-associated IPSPs in LGNd relay cells exhibited a mean reversal pote ntial of -86 mV. This reversal potential was shifted to more depolariz ed membrane potentials with the intracellular injection of Cl- through the use of KCl-filled microelectrodes. Simultaneous recording from th e perigeniculate nucleus (PGN) and LGNd revealed the IPSPs to be synch ronous with the occurrence of burst firing in the PGN. Excitation of P GN neurons with local electrical stimulation after pharmacological blo ck of excitatory amino acid transmission resulted in bicuculline-sensi tive IPSPs in relay neurons similar in amplitude and time course to th ose occurring during spindle waves. 4. Application of (-)-bicuculline methiodide resulted in the abolition of spindle wave associated IPSPs or in the slowing of the rate of rise, an increase in amplitude and a prolongation of these IPSPs; this resulted in a synchronized 2-4 Hz os cillation, in which each relay cell strongly burst on nearly every cyc le, thus forming a paroxysmal event. Bath application of the GABA(B) r eceptor antagonist 2-OH-saclofen blocked these slowed oscillations, in dicating that they are mediated by the activation of GABA(B) receptors . In contrast, pharmacological antagonism of GABA(B) receptors did not block the generation of normal spindle waves. 5. These and other resu lts indicate that spindle waves are generated in the ferret LGNd in vi tro as a network phenomenon occurring through an interaction between t he relay cells of the LGNd and the GABAergic neurons of the PGN. We pr opose that burst firing in PGN cells hyperpolarizes relay neurons thro ugh activation of GABA(A) receptors. These IPSPs result in rebound bur st firing in LGNd cells, which then excite PGN neurons. Block of GABA( A) receptors results in the transformation of spindle waves into event s resembling those associated with absence (spike-and-wave) seizures t hrough the increased activation of GABA(B) receptors and the subsequen t increase in duration and amplitude of IPSPs occurring during each cy cle of oscillation.