Lithium Enhances the GABAergic Synaptic Activities on the Hypothalamic Preoptic Area (hPOA) Neurons.

Santosh Rijal,Seong Kyu Han,Soo Joung Park,Seon Hui Jang

doi:10.3390/ijms22083908

Abstract

Lithium (Li+) salt is widely used as a therapeutic agent for treating neurological and psychiatric disorders. Despite its therapeutic effects on neurological and psychiatric disorders, it can also disturb the neuroendocrine axis in patients under lithium therapy. The hypothalamic area contains GABAergic and glutamatergic neurons and their receptors, which regulate various hypothalamic functions such as the release of neurohormones, control circadian activities. At the neuronal level, several neurotransmitter systems are modulated by lithium exposure. However, the effect of Li+ on hypothalamic neuron excitability and the precise action mechanism involved in such an effect have not been fully understood yet. Therefore, Li+ action on hypothalamic neurons was investigated using a whole-cell patch-clamp technique. In hypothalamic neurons, Li+ increased the GABAergic synaptic activities via action potential independent presynaptic mechanisms. Next, concentration-dependent replacement of Na+ by Li+ in artificial cerebrospinal fluid increased frequencies of GABAergic miniature inhibitory postsynaptic currents without altering their amplitudes. Li+ perfusion induced inward currents in the majority of hypothalamic neurons independent of amino-acids receptor activation. These results suggests that Li+ treatment can directly affect the hypothalamic region of the brain and regulate the release of various neurohormones involved in synchronizing the neuroendocrine axis.

Highlights

Gamma-aminobutyric acid (GABA) is well known to be a major inhibitory neurotransmitter in the central nervous system (CNS) [1]
In the hypothalamic preoptic area, GABA and glutamate mediate most of the fast postsynaptic potentials/events, indicating that neuronal communications in the hypothalamic area are due to amino acid neurotransmitters [9]
Li+ Enhances the Frequency of Spontaneous Inhibitory Postsynaptic Currents spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded from hypothalamic preoptic area (hPOA) neurons in the presence of ionotropic glutamate receptor blockers CNQX and AP5

Summary

Introduction

Gamma-aminobutyric acid (GABA) is well known to be a major inhibitory neurotransmitter in the central nervous system (CNS) [1]. Various physiological and pathological conditions continuously modulate the strength and polarity of GABAergic transmission in the CNS [4]. The hypothalamic area of the CNS contains GABAergic and glutamatergic neurons and their receptors that regulate various hypothalamic functions such as the release of neurohormones, control circadian activities [5]. In the hypothalamic preoptic area (hPOA), GABA and glutamate mediate most of the fast postsynaptic potentials/events, indicating that neuronal communications in the hypothalamic area are due to amino acid neurotransmitters [9]. GABA in the hypothalamic area exerts multiple effects on the hypothalamic-pituitary system. It is involved in the physiological control of anterior pituitary hormones [10], and regulation of the neuroendocrine system [6]. The hPOA is critically involved in several homeostatic processes such as sleep, reproduction, osmolality, body temperature, and behavior process as most brain regions have interconnections to the hPOA [11]

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