Development of hyperpolarizing inhibitory postsynaptic potentials and hyperpolarizing response to gamma-aminobutyric acid in rabbit hippocampus studied in vitro

Abstract

The postnatal development of IPSPs and response to locally applied GABA were examined using intracellular recording techniques in region CA1 of rabbit hippocampal slices maintained in vitro. Pyramidal neurons in slices from mature rabbits demonstrated an EPSP-IPSP sequence following stimulation of stratum radiatum. In these same slices, pressure application of GABA into stratum pyramidale and stratum radiatum produced membrane hyperpolarization and depolarization, respectively. Pyramidal neurons in slices from immature rabbits (age 6 to 10 days) responded differently. Stimulation of stratum radiatum produced a prolonged depolarizing postsynaptic potential; few IPSPs were observed. Ejection of GABA into either stratum pyramidale or stratum radiatum evoked a depolarizing response. The GABA agonist, 4,5,6,7-tetrahydroisoxazolo [5,4-c] pyridine-3-ol (THIP), which has been reported to activate "hyperpolarizing" GABA receptors selectively, primarily produced membrane hyperpolarization when applied to the somata of mature neurons, but it evoked a depolarization when applied to immature neurons. Bicuculline, a GABA antagonist which may have a preferential selectivity for "depolarizing" GABA receptors, was somewhat more efficacious (at 50 microM concentration) at antagonizing GABA-evoked depolarization in immature cells than GABA-evoked hyperpolarization in mature cells. This same concentration of bicuculline partially antagonized IPSPs in mature cells, and it markedly potentiated depolarizing PSPs in immature cells. Taken together, these results suggest that the late development of synaptic inhibition in rabbit hippocampus is due, at least in part, to an immaturity in the GABAergic system.

Enhanced activation of NMDA receptor responses at the immature retinogeniculate synapse

“…Late developmental changes in the efficacy of inhibition is not unique to the developing LGNd, but has also been reported in neocortex (Luhmann and Prince, 1990;Agmon and O'Dowd, 1993;Burgard and Hablitz, 1993) hippocampus (Harris and Teyler, 1983;Mueller et al, 1984;Swann et al, 1989), and piriform cortex (Schwab et al, 1984). Thus, late functional maturation of inhibitory connectivity may represent a general mech- Figure 6.…”

Ion Channel Development, Spontaneous Activity, and Activity-Dependent Development in Nerve and Muscle Cells

“…34, 469,470). Some of the early reports of this phenomenon were of experiments done in hippocampus (430,431). That spontaneous activity in hippocampus depends on excitatory GABA transmission is apparent from both the effects of GABA A blockers on activity (see above) and from the fact that the developmental disappearance of spontaneous GDPs parallels closely the switchover to inhibitory GABA A action (283).…”

“…34, 469, 470). It has been known for some time that GABA action was depolarizing and functionally excitatory in many developing neurons (35,44,307,353,355,359,430,431,446). Experiments using the gramicidin perforated patch method of whole cell recording, which does not disrupt intracellular chloride levels, subsequently showed that the excitatory action of GABA was not caused by a unique GABA receptor, but by elevated intracellular Cl Ϫ concentrations early in development (468,505).…”

Slow Kinetics of Miniature IPSCs during Early Postnatal Development in Granule Cells of the Dentate Gyrus

“…Previous studies have shown that GABAergic neurons are born prenatally (Schlessinger et al, 1978;Amaral and Kurz, 1985;Lubbers et al, 1985), and by the end of the first postnatal week, they make synaptic contacts on granule cell dendrites as well as somata (Lubbers and Frotscher, 1988;Ribak, 1988, 1990). Although GABAergic responses have been shown to occur in developing hippocampal and cortical pyramidal cells (Mueller et al, 1984;Kriegstein et al, 1987;Janigro and Schwartzkroin, 1988;Ben-Ari et al, 1989;Gaiarsa et al, 1990;Blanton and Kriegstein, 1991;Luhmann and Prince, 1991;Zhang et al, 1991;Hosokawa et al, 1994;Fleidervish and Gutnick, 1995), the functional properties of the early GABA A receptormediated synaptic transmission in the late-developing dentate granule cells are not well understood. The data presented here demonstrate that the overwhelming majority of dentate granule cells of the early postnatal rat possess functionally active GABAergic synaptic inputs [interestingly, no glutamatergic synaptic events can be observed at this time in granule cells (our unpublished observations)], similar to CA1 and CA3 pyramidal cells (Ben-Ari et al, 1989;Hosokawa et al, 1994;Gaiarsa et al, 1995).…”