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Excitatory actions of GABA in developing rat hypothalamic neurones
G Chen1, P Q Trombley, A N van den Pol
1Section of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA.
The Journal of Physiology
|July 15, 1996
Summary
Gamma-aminobutyric acid (GABA) neurotransmission shifts from excitatory to inhibitory in developing rat hypothalamic neurons. This change is due to a negative shift in the chloride reversal potential, impacting neuronal activity during development.
Area of Science:
- Neuroscience
- Developmental Biology
- Neurophysiology
Background:
- Gamma-aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the mature central nervous system.
- However, GABAergic signaling can be excitatory during early neuronal development.
- The developmental trajectory of GABAergic function in hypothalamic neurons is not fully understood.
Purpose of the Study:
- To investigate the developmental changes in GABA-mediated responses in rat hypothalamic neurons.
- To determine the underlying mechanisms for shifts in GABAergic signaling from potentially excitatory to inhibitory.
- To elucidate the role of chloride ion (Cl-) concentration and reversal potential in GABAergic function during development.
Main Methods:
- Gramicidin-perforated patch clamp recordings were used to assess GABA-mediated responses in rat hypothalamic neurons at different developmental stages (1-7 days in vitro and 20-33 days in vitro).
- Intracellular Cl- concentration was maintained at physiological levels using the gramicidin-perforated patch configuration.
- Dose-response curves, reversal potential measurements, and bicuculline blockade were employed to characterize GABAergic receptor function.
Main Results:
- In young neurons (1-7 DIV), GABA induced depolarizing membrane potentials and increased neuronal activity, with an EC50 of 2.8 microM.
- In older neurons (20-33 DIV), GABA induced hyperpolarizing membrane potentials and decreased neuronal activity.
- The reversal potential for GABA-evoked currents shifted from -40 to -50 mV in young cultures to below -70 mV in older cultures, indicating a developmental shift in Cl- gradient.
- Synaptically released GABA also mediated excitatory transmission in young cultures, as evidenced by bicuculline-sensitive depolarizing postsynaptic potentials.
- GABA-evoked depolarization could trigger action potentials in young neurons, with its net effect (excitatory or inhibitory) depending on the reversal potential and temporal integration.
Conclusions:
- The reversal potential of GABA-evoked currents becomes more negative during the development of rat hypothalamic neurons.
- This developmental shift in Cl- reversal potential underlies the transition of GABAergic signaling from excitatory to inhibitory.
- GABA neurotransmission plays dual roles, both excitatory and inhibitory, during early hypothalamic development.