GABA Actions in Hippocampal Area CA3 During Postnatal Development: Differential Shift From Depolarizing to Hyperpolarizing in Somatic and Dendritic Compartments
Abstract
γ-Aminobutyric acid type A receptor (GABA A-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 GABA A-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 GABA A-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.
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Around the second postnatal week in rodents (~first postnatal week in human), the depolarizing effect of GABA slowly transitions into an inhibitory net effect depending on place and time.
“Around the second postnatal week in rodents (~first postnatal week in human), the depolarizing effect slowly transitions into an inhibitory net effect depending on place and time [189, 190].”
From Development of prefrontal cortex (2022) · cites this paper as [190]
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“Around the second postnatal week in rodents (~first postnatal week in human), the depolarizing effect slowly transitions into an inhibitory net effect depending on place and time [189, 190].”
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- Authors
- Romo-Parra, H., Treviño, M., Heinemann, U., & Gutiérrez, R.
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 2008-03
- Volume
- 99
- Issue
- 3
- Pages
- 1523-1534
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- OpenAlex
- W2090412624
- Cited by
- 52
- References
- 46
- Citations by year
- 2025: 2 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 5 · 2012: 3
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Keywords
- GABAA receptor, hippocampal CA3, postnatal development, dendritic compartments, pyramidal neurons, dentate gyrus, reversal potential, current source density, inhibitory postsynaptic potentials
- MeSH terms
- Age Factors, Animals, Animals, Newborn, Dendrites, Dose-Response Relationship, Radiation, Electric Stimulation, gamma-Aminobutyric Acid, Hippocampus, Membrane Potentials, Muscimol, Neural Inhibition, Neurons, Pyridazines, Quinoxalines, Valine, Rats, Wistar, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists, GABA Agonists, GABA Antagonists, Rats
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