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J Neurophysiol 99: 1523-1534, 2008. First published January 23, 2008; doi:10.1152/jn.01074.2007
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GABA Actions in Hippocampal Area CA3 During Postnatal Development: Differential Shift From Depolarizing to Hyperpolarizing in Somatic and Dendritic Compartments

Héctor Romo-Parra1,*, Mario Treviño1,*, Uwe Heinemann2 and Rafael Gutiérrez1

1Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y Estudios Avanzados, Mexico Federal District; and 2Johannes-Müller Center of Physiology, Institute of Neurophysiology, Charité Universitätsmedizin, Berlin, Germany

Submitted 27 September 2007; accepted in final form 21 January 2008

{gamma}-Aminobutyric acid type A receptor (GABAA-R) activation leads to depolarization of pyramidal cells during the first postnatal week and produces hyperpolarization from the second week. However, immunohistochemical evidence has suggested that during the second and third postnatal weeks the NKCC1 cotransporter relocates from the soma to the dendrites of CA3 pyramidal cells. We hypothesized that this leads to depolarizing responses in apical dendrites. Here we show that the activation of GABAA-R in the distal dendrites of CA3 pyramidal cells at P15 by restricted application of muscimol or synaptic activation by stimulation of interneurons in stratum radiatum (SR) causes depolarizing postsynaptic potentials (PSPs), which are blocked by NKCC1 cotransporter antagonists. By contrast, activation of proximal GABAA-R by muscimol application or by stimulation of interneurons in s. oriens (SO) leads to hyperpolarizing PSPs. Activation of the dentate gyrus (DG) in the presence of glutamatergic blockers evokes hyperpolarizing responses during the second postnatal week; however, the reversal potential of the DG-evoked inhibitory (I)PSPs is more depolarized than that of IPSPs evoked by activation of SO interneurons. Despite the shift of GABA action from depolarizing to hyperpolarizing, DG-evoked field potentials (f-PSPs) recorded in s. lucidum/radiatum (SL/R) do not change in polarity until the third week. Current source density analysis yielded results consistent with depolarizing actions of GABA in the dendritic compartment. Our data suggest that GABAergic input to apical dendrites of pyramidal cells of CA3 evokes depolarizing PSPs long after synaptic inhibition has become hyperpolarizing in the somata, in the axon initial segments and in basal dendrites.


Address for reprint requests and other correspondence: R. Gutiérrez, Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Apartado Postal 14-740, 07000 Mexico D.F. (E-mail: grafael{at}fisio.cinvestav.mx)




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B. Lasztoczi, G. Nyitrai, L. Heja, and J. Kardos
Synchronization of GABAergic Inputs to CA3 Pyramidal Cells Precedes Seizure-Like Event Onset in Juvenile Rat Hippocampal Slices
J Neurophysiol, October 1, 2009; 102(4): 2538 - 2553.
[Abstract] [Full Text] [PDF]




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