Development of GABA‐mediated, chloride‐dependent inhibition in CA1 pyramidal neurones of immature rat hippocampal slices.

Abstract

SUMMARY1. y-Aminobutyric acid (GABA)-mediated, Cl--dependent inhibitory postsynaptic potentials (IPSPs) and GABA currents in immature rat hippocampal CAI neurones were studied using the whole-cell recording technique in brain slices.2. IPSPs evoked by electrical stimulation were observed in postnatal 2-to 5-(PN2-5), 8-to 13-(PN8-13) and 15-to 20-(PN15-20)day-old CAI neurones. In the presence of glutamate receptor blockers 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D-2-amino-5-phosphonovaleric acid (APV), the reversal potential for the IPSP (ElPSP) was near the resting membrane potential (RMP) in the PN2-5 neurones, but 13 and 25 mV more negative than the RMP in PN8-13 and PN15-20 neurones respectively. IPSPs and GABA currents were blocked by the GABAAreceptor antagonists bicuculline or picrotoxin.3. The reversal potential for somatic GABA currents (EGABA) was examined in the presence of tetrodotoxin (TTX). There was a strong dependence of the EGABA upon the patch pipette [Cl-] ([CI-]p), indicating that the GABA currents were mediated by a Cl-conductance. In PN2-5 neurones, EGABA agreed with the value predicted by the Goldman-Hodgkin-Katz equation at given concentrations of internal and external anions permeable through GABA-activated Cl-channels, whereas EGABA in older neurones was 8-18 mV more negative.4. Examination of the relations between EGABA, holding potential, [Cl-]p and resting conductance indicated that the membrane of the PN2-5 neurones was readily permeable to Cl-which followed a passive Donnan equilibrium. Passive distribution of Cl-played a decreasing role in PN8-13 neurones and in PN1S-20 neurones.5. To assess the contribution of outward Cl-co-transport, bath applications of high K+ or furosemide were performed. High K+ and furosemide caused a reversible positive shift of EGABA in PN15-20 neurones. Raising the temperature moved EGABA to a more negative potential, with a Qlo of 5 mV. A similar change of EGABA in response to high K+, but not to furosemide, was found in PN8-13 neurones.6. The present data indicate the existence of GABAA-mediated inhibitory synaptic connections in CAI neurones at the earliest stages of postnatal life. During the first postnatal week, Cl-ions are passively distributed and the EIPSP and EGABA NS 9102 L. ZHANG, I. SPIGELMAN AND P. L. CARLEN are near the RMP. After the first postnatal week, EIPSP and EGABA move to potentials more negative than the RMP, partly due to the gradual development of Cl-extrusion system(s), thereby maintaining a driving force for hyperpolarizing IPSPs at the resting potential in the more mature neurones.

Mice deficient for prion protein exhibit normal neuronal excitability and synaptic transmission in the hippocampus.

“…The voltage-current relation of the monosynaptic fast IPSP was established by shifting the membrane potential from around -110 to -50 mV (Fig. 2) (19,20); therefore, one possibility that could explain the discrepancy between our results and those from others (12, 13) is the age of the animals. The age of the mice used in the latter study was not specified, and so we also carried out a study with older animals.…”

Exercise Modulates Chloride Homeostasis after Spinal Cord Injury

“…Before CNS maturation, high [Cl Ϫ ] i results in Cl Ϫ efflux at resting membrane potential, which depolarizes the neurons and can even evoke action potentials ( Fig. 9, left; Zhang et al, 1991;Ehrlich et al, 1999;Kakazu et al, 1999). After maturation, low [Cl Ϫ ] i causes a chloride influx during channel opening that results in hyperpolarization (Fig.…”

Oligomerization of KCC2 Correlates with Development of Inhibitory Neurotransmission

“…In the vast majority of mature neurons, a low intracellular chloride concentration ([Cl Ϫ ] i ) causes Cl Ϫ influx during channel opening, resulting in hyperpolarization (Eccles, 1966;Kaila, 1994). In contrast, a high [Cl Ϫ ] i in immature neurons results in Cl Ϫ efflux at the resting membrane potential (Zhang et al, 1991;Wang et al, 1994;Obrietan and van den Pol, 1995;Ehrlich et al, 1999;Kakazu et al, 1999). This efflux depolarizes the neurons and can even elicit action potentials.…”