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Ai-Hui Tang Ph.D.

Academic Title: Assistant Professor
Primary Appointment: Physiology
Location: Howard Hall 517
Phone: 410-706-0515

Personal History:

I completed undergraduate work and obtained my Ph.D. in Peking University. My thesis was on intracellular calcium dynamics in single cardiac cells. My postdoctoral training was with Bradley Alger in Department of Physiology at UMAB.

Research Interests:

My long-term goal is to understand the mechanisms of the regulation of neuronal communication and excitability in the central nervous system. Hippocampus is a brain formation that is critical for learning and memory and involved in severe mental illnesses including schizophrenia and depressions. I use hippocampus as a model system to study neurophysiology at levels from the structural architecture of single synapses, to the modulation of synaptic transmission, and ideally to network interactions among neurons. Electrophysiological, optical, and genetic methods have been particularly key in investigating these mechanisms.

Synaptic transmission is maintained by a delicate sub-synaptic architecture, and disease-related functional impairments may result from even mild abnormalities in synapse structure. Key to this architecture is how the distribution of vesicle fusion sites at presynaptic terminals corresponds to the position of receptors on the postsynaptic neurons. Despite long recognition that this distribution modulates synaptic strength, it has not been precisely described, due in part to the limited resolution of light microscopy which does not provide sufficient resolution to examine subsynaptic structure.  To get around this barrier, I adapted the 3-dimensional super-resolution STORM imaging technique and developed extensive new analysis approaches by working with Tom Blanpied; now I can achieve a imaging resolution of < 20 nm in lateral and of ~50 nm in axial. This enables me to deal with the central question by directly measuring the distribution of key proteins involved in organizing presynaptic vesicle fusion and postsynaptic neurotransmitter receptors in cultured hippocampal neurons. I discovered a previously unknown level of subsynaptic organization whereby these two fundamental elements are transsynaptically aligned with ~60 nm precision.  This architectural principle may be common to many or the majority of synapses in the CNS and may be a critical mechanism for regulating their strength and plasticity.

Nervous system function relies on coordinated activity among large populations of neurons. Thus, to me, it will be essential to understand how different types of neurons are connected and how these connections are modulated in the real brain circuitry. As an example of this in my work with Brad Alger, I investigated the connections between two different identified kinds of inhibitory interneurons (PV+ and CCK+) and their synapses onto the principal pyramidal neurons in preparation of hippocampal tissue slice. Using patch-clamping and optogenetic technique, I discovered previously unknown connections between these two interneuron populations and a new mode of nicotinic acetylcholine receptor initiated T-type calcium channel dependent neurotransmitter release at synapses between PV+ interneurons and the principal cells. These connections may affect large scale rhythmic oscillations that associate with certain behaviors.

On the other hand, the endocannabinoid (eCB) dependent plasticity of synaptic transmission has been a major focus of my study. eCB is a group of neuromodulatory lipids and their receptors in the brain are involved in a variety of physiological processes including appetite, mood and memory. In hippocampus, eCB receptors are extensively distributed on the presynaptic terminal of CCK+ interneurons. I studied the metabotropic glutamate receptor mediated eCB mobilization at the inhibitory synapse between these interneurons and the pyramidal cells. Studies in cultured expression systems have found an important role of a scaffold protein (Homer) in coupling mGluR and eCB synthesizing enzyme structurally and functionally at excitatory synapses. While testing this model at inhibitory synapses in intact brain tissue slice, I discovered an opposite modulation of mGluR mediated eCB mobilization by this scaffold protein. This new mechanism enables Homer and eCB to shift the balance between excitation and inhibition under different circumstances and underlies the hyperexcitability in a mouse model of fragile X syndrome.

Such work is critical not only to our understanding of physiological phenomena such as learning and memory, but also the effects of drugs such as marijuana, and pathophysiological processes, such as Alzheimerâ?Ts disease and Fragile X Syndrome.

Lab Techniques and Equipment:

  • Preparations: acute in vitro hippocampal slices; cultured hippocampal neurons.
  • Electrophysiological techniques: intracellular and extracellular recordings; single or dual whole-cell voltage and current clamp.
  • Imaging techniques: Super-resolution STORM imaging, intracellular calcium-imaging, and confocal and two-photon microscopy to study labeled cells in slices; infra-red, differential interference contrast visualization of cells in living slices.


Tang AH and Alger BE (2015) Homer protein-metabotropic glutamate receptor binding regulates endocannabinoid signaling and affects hyperexcitability in a mouse model of Fragile X Syndrome. J Neurosci. 35(9):3938-45.

Alger BE, Nagode DA and Tang AH (2014) Muscarinic cholinergic receptors modulate inhibitory synaptic rhythms in hippocampus and neocortex. Front Synaptic Neurosci. 6:18.

Nagode DA, Tang AH, Yang K and Alger BE (2014) Optogenetic identification of an intrinsic cholinergically driven inhibitory oscillator sensitive to cannabinoids and opioids in hippocampal CA1, J Physiol. 592(Pt 1):103-23.

Alger BE and Tang AH (2012) Do cannabinoids reduce brain power? Nat Neurosci. 15:499-501.

Nagode DA, Tang AH, Karson MA, Klugmann M and Alger BE (2011) Optogenetic release of ACh induces rhythmic bursts of  perisomatic IPSCs in hippocampus, Plos One, 6(11):e27691. (Co-first Author)

Tang AH, Nagode DA, Karson MA, McIntosh JM, Uebele V, Renger J, Milner T, Klugmann M and Alger BE (2011) Nerve terminal nAChRs initiate quantal GABA release from perisomatic interneurons by activating axonal T-type (Cav3) Ca2+ channels and Ca2+ release from stores. J Neurosci, 31: 13546 - 13561.

Karson MA, Tang AH, Milner T and Alger BE (2009) Synaptic cross-talk between perisomatic-targeting interneuron classes in hippocampus. J Neurosci. 29: 4140-4154. (Co-first Author)

Links of Interest:

Lab Website