Development of GABA_A Receptor-Mediated Inhibitory Postsynaptic Currents in Hippocampus

Abstract

Development of GABA A receptor-mediated inhibitory postsynaptic currents in hippocampus. J Neurophysiol 88: 3097-3107, 2002; 10.1152/jn.00026.2002. Hippocampal CA1 pyramidal cells receive two kinetic classes of GABA A receptor-mediated inhibition: slow dendritic inhibitory postsynaptic currents (GABA A,slow IPSCs) and fast perisomatic (GABA A,fast ) IPSCs. These two classes of IPSCs are likely generated by two distinct groups of interneurons, and we have previously shown that the kinetics of the IPSCs have important functional consequences for generating synchronous firing patterns. Here, we studied developmental changes in the properties of GABA A,fast and GABA A,slow spontaneous, miniature, and evoked IPSCs (sIPSCs, mIPSCs, and eIPSCs, respectively) using whole cell voltage-clamp recordings in brain slices from animals aged P10 -P35. We found that the rate of GABA A,slow sIPSCs increased by over 70-fold between P11 and P35 (from 0.0017 to 0.12 s Ϫ1 ). Over this same age range, we observed a Ͼ3.5-fold increase in the maximal amplitude of GABA A,slow eIPSCs evoked by stratum lacunosummoleculare (SL-M) stimuli. However, the rate and amplitude of GABA A,slow mIPSCs remained unchanged between P10 and P30, suggesting that the properties of GABA A,slow synapses remained stable over this age range, and that the increase in sIPSC rate and in eIPSC amplitude was due to increased excitability or excitation of GABA A,slow interneurons. This hypothesis was tested using bath application of norepinephrine (NE), which we found at low concentrations (1 M) selectively increased the rate of GABA A,slow sIPSCs while leaving GABA A,fast sIPSCs unchanged. This effect was observed in animals as young as P13 and was blocked by coapplication of tetrodotoxin, suggesting that NE was acting to increase the spontaneous firing rate of GABA A,slow interneurons and consistent with our hypothesis that developmental changes in GABA A,slow IPSCs are due to changes in presynaptic excitability. In contrast to the changes we observed in GABA A,slow IPSCs, the properties of GABA A,fast sIPSCs remained largely constant between P11 and P35, whereas the rate, amplitude, and kinetics of GABA A,fast mIPSCs showed significant changes between P10 and P30, suggesting counterbalancing changes in action potential-dependent GABA A,fast sIPSCs. These observations suggest differential developmental regulation of the firing properties of GABA A,fast and GABA A,slow interneurons in CA1 between P10 and P35.

Early Enriched Environment Promotes Neonatal GABAergic Neurotransmission and Accelerates Synapse Maturation

“…General characteristics of the maturation of GABAergic synapses (Hollrigel and Soltesz, 1997;Dunning et al, 1999;Huntsman and Huguenard, 2000;Banks et al, 2002), including developmental increases in mGPSC frequency, reduction in mGPSC amplitude, and faster kinetics ( Fig. 1G,H; Table 1) were observed in both groups.…”

Noradrenergic Modulation of Electrical Coupling in GABAergic Networks of the Hippocampus

“…First, noradrenergic modulation of intrinsic conductances in interneurons has been repeatedly shown (Bergles et al, 1996;Maccaferri and McBain, 1996, Parra et al, 1998, Banks et al, 2002. Therefore, we wanted to avoid the assumption that modulation of coupling indexes must reflect modulation of the junctional conductance across the pair.…”

“…Indeed, the rate of spontaneous IPSCs mediated by "slow" GABA A receptors (GABA A, slow ) (Pearce, 1993), which may originate from neurogliaform interneurons (Price et al, 2005;Szabadics et al, 2007), has been reported to be selectively increased by low doses of NA (Banks et al, 2002). However, without a parallel effect on coupling, it would be difficult to explain how this powerful excitation of a GABAergic network would not translate into phasic synchronized epileptiform activity.…”

Neuronal Differentiation in the Adult Hippocampus Recapitulates Embryonic Development

“…S2 A, available at www.jneurosci.org as supplemental material), consistent with the slow kinetics exhibited by evoked PSCs. The slow kinetics of GABAergic PSCs suggests a dendritic localization of the early GABAergic connections (see Discussion) (Miles et al, 1996;Banks et al, 1998Banks et al, , 2002). These findings demonstrate that GABAergic interneurons are the primary source of synaptic inputs onto immature neurons in the adult hippocampus, similar to what occurs to CA1 pyramidal neurons and DGCs during development (Tyzio et al, 1999;Khazipov et al, 2001;Gozlan and Ben Ari, 2003).…”

“…In contrast, the order of appearance of fast and slow GABAergic afferents in the developing hippocampus has not been clearly established. Although the existence of principal neurons displaying exclusively slow GABAergic PSCs has not yet been confirmed by electrophysiological recordings in the developing hippocampus (Hollrigel and Soltesz, 1997;Banks et al, 2002), anatomical studies indicate that dendritic GABAergic synapses are formed before somatic ones. In a previous study, Lüb-bers and Frotscher (1988) showed that immature DGCs in P5 rats received mostly GABAergic afferents impinging onto dendritic shafts.…”