Abstract
The intraneuronal chloride concentration ([Cl-]i) is paramount for determining the polarity of signaling at GABAA synapses in the central nervous system. Sectioning hippocampal brain slices increases [Cl-]i in the superficial layers. It is not known whether cutting trauma also increases [Cl-]i in the neocortex and thalamus, and whether the effects of trauma change during development. We used Cl- imaging to study the [Cl-]i vs. the distance from the cut surface in acute thalamocortical slices from mice at developmental ages ranging from post-natal day 5 (P5) to P20. We demonstrate: 1) [Cl-]i is higher in the most superficial areas in both neocortical and thalamic brain slices at all ages tested and, 2) there is a developmental decrease in [Cl-]i that is independent of acute trauma caused by brain slicing. We conclude that [Cl-]i has a developmental progression during P5-20 in both the neocortex and thalamus. However, in both brain regions and during development the neurons closest to the slicing trauma have an elevated [Cl-]i.
Highlights
The action of GABA through GABAA receptors is primarily mediated by the flow of Cl- and to a lesser extent, bicarbonate (HCO3-) [1]
If EGABA is more negative than resting membrane potential (RMP), GABAA receptor activation will inhibit the neuron by membrane hyperpolarization. [Cl-]i decreases in a rostral-caudal sequence during development and the neocortex is one of the last regions to develop low [Cl-]i [4,5]
We conclude that neuronal [Cl-]i decreases with development throughout the P5-20 interval in both neocortex and thalamus, and that this progressive decrease is independent of slicing trauma
Summary
The action of GABA through GABAA receptors is primarily mediated by the flow of Cl- and to a lesser extent, bicarbonate (HCO3-) [1]. If ECl is significantly more positive than the RMP of a neuron, GABAA receptor activation will depolarize the membrane and lead to excitation or shunting inhibition [2,3]. If EGABA is more negative than RMP, GABAA receptor activation will inhibit the neuron by membrane hyperpolarization. Recent data in the hippocampus illustrated that traumatic sectioning of brain slices increases the [Cl-]i in the most superficial neuronal layer [6]. This data raised the possibility that slicing artifacts might have contributed to the observed elevated [Cl-]i during early development [7,8].
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