Research interests:
GABA and glutamate are the most prevalent neurotransmitters in central nervous system (CNS), which mediate inhibitory and excitatory transmissions, respectively. Imbalance between inhibitory and excitatory transmissions has been implicated in the pathogenesis of various CNS diseases, including neuronal developmental disease (e.g. sexual differentiation), epilepsy, and schizophrenia. On the other hand, the CNS neurons are often surrounded by astrocyte processes, in which transporters located on astrocyte membrane, play a pivotal role in the inactivation of GABAergic and glutamatergic neuronal transmissions. The astrocytic glutamine-glutamate cycle (see Figure 1 cartoon below) is a typical example of amino acids metabolic interaction between neurons and astrocytes that could modulate GABAergic and glutamatergic synaptic strengths during brain development and under brain diseases.

Figure 1. Vesicular neurotransmitter(s) originating from the glutamine - glutamate cycle may depend on astrocytic synthesis and transport. Illustrated are the three cellular components of a glutamatergic synapse: the pre- and post-synaptic elements, which are often surrounded by astrocytic processes. The primary transporters regulating presynaptic uptake of glutamate (Glu, n ; EAAC-1) is shown on the face of the synapse. The Glu-glutamine (Gln) cycle pathway is indicated by the thick arrows, starting with astrocytes uptake Glu through GLT-1, and convert Glu into Gln via glutamine synthetase (Gln, l). Gln can then be transported out through System-N transporters (SN-1) and into the neuron through System-A transporters (SA-1). Neurons use Gln to synthesize Glu via glutaminase. The Glu can then be packaged into the vesicle via vesicular Glu transporters (vGluT).
Use a variety of electrophysiology techniques in conjunction with pharmacological interventions, qualitative and quantitative mRNA and protein analysis as well as behavioral tests, three research topics are currently on going in my lab:
- Cellular mechanisms of the GGC on the regulation of glutamatergic and GABAergic synaptic transmissions during brain sex differentiation in rats.
- Cellular mechanism of CART peptides on firing rates and synaptic inputs of DMV neurons innervating stomach and cecum in rats.
- Cellular mechanisms of the GGC in the regulation of GABAergic synaptic transmissions in temporal lobe epilepsy in rats.
Research approach:
- Adapting visualized whole-cell voltage and current clamp recordings techniques, inhibitory and excitatory postsynaptic currents (IPSCs; EPSCs), firing activity used cell-attached technique are routinely used to examine the changes of synaptic functions, in which several parameters are used and listed below:
- Miniature IPSCs (mIPSCs), miniature EPSCs (mEPSCs) for testing changes in synaptic efficacy under basal condition of synaptic activities.
- Strontium evoked IPSCs and EPSCs; miniature evoked IPSCs (meIPSCs) and miniature evoked EPSCs (meEPSCs) for testing changes in potency and release probability under active synapses.
- Recording spontaneous IPSCs (sIPSCs), spontaneous EPSCs (sEPSCs), evoked IPSCs (eIPSCs), evoked EPSCs (eEPSCs) and field excitatory postsynaptic potential (fEPSP) to assess synaptic efficacy.
- Paired-pulse stimulation recordings to determine changes in synaptic vesicle’s release probability.
- Puffed GABA or glutamate for testing changes in postsynaptic receptors’ numbers or sensitivity.
- Pair-recordings to directly assess synaptic interaction between pre- and post-synaptic neurons.
- Astrocytic GABA and glutamate transporter currents recordings to reflex extracellular GABA and glutamate concentration.
- Western blotting analysis for semi-quantification protein levels of interested proteins.
- Quantitative RT-PCR for evaluation RNA levels.
- Immunocytochemistry for post hoc analysis of recorded neuron.
- Animal behavior observation and identification, including reproductive behavioral tests
List of Publications (2012-present):
Journal Articles (peer-reviewed):
- Liang SL*, Tong YS, Hwang LL, Huang YZ, Chen CY, (2021) CART peptides differently regulate firing rates and GABAergic synaptic inputs of DMV neurons innervating the stomach and cecum of adult male rats. Neuroendocrinology (Revised)
- Liang SL (2018) The glutamate-glutamine cycle regulates synaptic glutamate release in ventrolateral ventromedial nucleus of the hypothalamus of perinatal female rats. J. Neuroendocrinol. 30: e12642.
- Liang SL*, Alger BE, McCarthy MM (2014) Developmental increase in hippocampal endocannabinoid mobilization: roles of metabotropic glutamate receptor subtype 5 and phospholipase C. J. Neurophysiol. 112:2605-2615. (*, corresponding author).
- Liang SL*, Hsu SC, Pan JT (2014) Involvement of dopamine D2 receptor in the diurnal changes of tuberoinfundibular dopaminergic neuron activity and prolactin secretion in female rats. J. BioMed. Sci. 21:37 (*, corresponding author).
- Liang SL*, Pan JT (2012) An endogenous dopaminergic tone acting on dopamine D3 receptors may be involved in diurnal changes of tuberoinfundibular dopaminergic neuron activity and prolactin secretion in estrogen-primed ovariectomized rats. Brain Res. Bull. 87:334-339. (*, corresponding author).
Published Abstracts
- Liang SL, Chen RS: Perinatal interruption of glutamine-glutamate cycle (GGC) permanently compromises GGC-dependent basal excitatory and inhibitory synaptic transmissions in the hypothalamic neurons of estrous female rats. The 35th Joint Annual Conference of Biomedical Science, Taiwan, Taipei. (Accepted)
- Lin YS, Liang SL: Blockade of neuronal glutamine uptake during brain development differently changes fertility of female rats. The 34th Joint Annual Conference of Biomedical Science, Taipei, Taiwan, Mar 23-24, 2019. (P061, enter the final poster contest held by The Chinese Physiological Society).
- Lin YS, Liang SL: Neonatal disruptions of the glutamate-glutamine cycle reduce the expression of sexual behavior and fertility of female rats. The 33th Joint Annual Conference of Biomedical Science, Taipei, Taiwan, Mar 24-25, 2018. (PY073).
- Tong YS, Hwang LL, Chen CY, Liang SL: Different regulations of CART peptides on firing rates and synaptic inputs of DMV neurons innervating stomach and cecum in rats. The 32th Joint Annual Conference of Biomedical Science, Taipei, Taiwan, Mar 25-26, 2017. (PY060).
- Tong YS, Hwang LL, Chen CY, Liang SL: Retrograde Labeling in vivo of vagal preganglionic neurons innervating stomach and cecum in rats by the carbocyanine dye DiO. The 31th Joint Annual Conference of Biomedical Science, Taipei, Taiwan, Mar 26-27, 2016. (P138).
- Yeh CY, Liang SL: Sex differential effects of neonatal pretreatments of fluoroacetate or MSO to disrupt glutamate-glutamine cycle on adult reproductive behaviors in rats. EMBO Conference on neural development- function and dysregulation. Taipei, Taiwan, Dec 4-8, 2015. (p32)
- Liang SL, Hsu SC: Diurnal changes of dopamine D2 and D3 receptor mRNA expression in medial basal hypothalamus of estrogen-primed ovariectomized rats. The 28th Joint Annual Conference of Biomedical Science, Taipei, Taiwan, Mar 23-24, 2013. (P564)
- Liang SL, Lim SC: Blockade of neuronal glutamine uptake reduces quantal GABA content under active synapse in the mediobasal hypothalamus of neonatal rats. The 27th Joint Annual Conference of Biomedical Science, Taipei, Taiwan, Mar 17-18, 2012. (P415)
Patents
1. Liang, S.L. (2019) Use of glutamine in improving sexual dysfunction. Taiwan, ROC. Patent No. I652059.
Chinese Articles
- 梁淑鈴 (2011, 十月):簡介腦神經疾病與星狀膠細胞麩胺酸—麩胺醯胺循環異常的關連。長庚醫訊,32卷10期,增刊第54-57頁。
Honors and Awards
- Lin YS, Liang SL: Neonatal disruptions of the glutamate-glutamine cycle reduce the expression of sexual behavior and fertility of female rats. Second place in the Master thesis contest held by Graduate Institute of Biomedical Sciences of Chang Gung University, Taiwan, Tauyuan, Jul 2-6, 2018. (2C09).
- Lin YS, Liang SL: Neonatal disruptions of the glutamate-glutamine cycle reduce the expression of sexual behavior and fertility of female rats. Third place in the poster contest held by The Chinese Physiological Society in the 33th Joint Annual Conference of Biomedical Science, Taiwan, Taipei, Mar 24-25, 2018. (PY073).
- Tong YS, Hwang LL, Chen CY, Liang SL: Different regulations of CART peptides on firing rates and synaptic inputs of DMV neurons innervating stomach and cecum in rats. Third place in the poster contest held by The Chinese Physiological Society in the 32th Joint Annual Conference of Biomedical Science, Taiwan, Taipei, Mar 25-26, 2017. (PY060).
- The Marsden Fund Referee, The Marsden Fund is affiliated by New Zealand Government and is administered by the Royal Society of New Zealand. 2014.
- Editorial Board Member in Journal “Animal Cells and Systems”, The Official Journal of the Korean Society for Integrative Biology. 2010~2013.
- National Science Council Outstanding Researcher Award, 2011.
International Affairs
1. Collaboration with lab of Coulter, D.A., Ph.D. (Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Division of Neurology and the Pediatric Regional Epilepsy Program, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA) in the epilepsy research project.
|