Education

MD
Beijing Medical University-Beijing, China

Doctorate in Biophysics
University of Rochester-Rochester, NY

Publications

Yang Q, Ahmad Abdulla, Farooq, M, Ishikawa Y and Liu S*. J. Adenylyl cyclase 5 mediates a stress-induced increase in GluA2 expression in cerebellar stellate cells. Cell Reports. 2025 Jan 28;44(1):115180.

Carzoli KL, Kogios, G, Patel J and Liu S. J*. (2023) Learning reduces hyperpolarization-activated cyclic nucleotide-gated current in cerebellar stellate cells. Cell Reports. 42(9): 113057

Dubois C, Katzman P and Liu S. J* (2021) GluN2D NMDA receptors gate fear extinction learning and interneuron plasticity. Frontiers in Synaptic Neuroscience.

Dubois C, Patel J, Katzman P and Liu S. J* (2020) Inhibitory neurotransmission drives endocannabinoid degradation during memory consolidation Nature Communications 11: 6407.

Bender CL, Sun XX, Farooq M, Yang Q, Davison C, Maroteaux M, Huang Y-S, Ishikawa Y, Liu SJ*. (2020) Emotional stress induces structural plasticity in Bergman glia via an AC5-CPEB3-GluA1 pathway. Journal of Neuroscience 40(17): 3374–3384.

Research

In addition to its well-studied role in motor control, the cerebellum sends outputs to a variety of non-motor brain regions including the prefrontal cortex and limbic system, and thus plays an important role in emotional regulation. One model for emotional learning and memory is Pavlovian fear conditioning, a form of associative fear memory. The cerebellum is required for the formation of this type of associative fear memory. Using this paradigm, our long-term goal is to identify the cerebellar neural correlates of emotional memory and to understand how psychological stress enhances associative learning. Over the last ten years, our research has evolved from the study of synaptic plasticity in brain slices to examining experience-induced changes in cerebellar network activity, and ultimately how neural plasticity alters animal behavior.

Emotional stress regulates glutamate receptor gene expression. Changes in emotional state are known to alter neuronal excitability and can modify learning and memory formation. In a recent study we have shown that a single exposure to a fear-inducing stimulus induces a long-lasting increase in the transcription of the GluR2 subunit of the AMPA-type glutamate receptor in cerebellar inhibitory interneurons (Liu et al, 2010). This reduces the AMPA receptor Ca²⁺ permeability and alters synaptic efficacy.

We are currently investigating how a stress hormone, noradrenaline, promotes the expression of the GluR2 gene in inhibitory interneurons and how enhanced GluR2 transcription in inhibitory interneurons changes the activity of cerebellar circuits. We detect changes in GluR2 mRNA levels using real time single cell RT-PCR, identify AMPA receptor subunit composition at individual synapses using electrophysiological techniques and monitor morphological changes using confocal microscopy. 

Fear memories and synaptic plasticity. Cerebellar lobule V/VI is critically involved in the consolidation of associative fear conditioning. We use DREADD technologies to selectively activate and suppress the activity of different types of cerebellar neurons to determine the role of these neurons in the formation of associative fear memory. We have identified several forms of cerebellar neuronal plasticity following fear conditioning (manuscripts submitted). We are particular interested in understanding the molecular mechanism(s) underlying learning-induced alterations in endocannabinoid signaling, AMPA receptor subtype expression, and lasting changes in the intrinsic excitability of cerebellar interneurons. In addition, we have started to determine the effect of these forms of neural plasticity on the activity of cerebellar neuronal circuits.

Topological Regulation of Synaptic AMPA Receptor Expression. In recent work we have demonstrated that action potential activity changes the expression of CPEB3 (an RNA binding protein) which interacts with GluA2 mRNA and controls GluA2 protein synthesis. This process is critically involved in establishing a GluA2 gradient along the dendrites of interneurons in the molecular layer of the cerebellum (Savtchouk et al, Cell Reports, 2016; Bender et al, Neuropharmacology, 2015). These studies demonstrate a cell-autonomous modulation of synaptic AMPAR expression that is controlled by postsynaptic AP firing.