Chu Laboratory

Neural Circuits and Neurodegeneration

Parkinson’s disease is a progressive, neurodegenerative disorder marked by loss of brain cells that produce dopamine, a neuromodulator that regulates voluntary movement and many other biological processes. As gradual depletion of dopamine in the brain and progressive degeneration of these critical cells occurs, the hallmark symptoms of Parkinson’s disease start to appear, including akinesia, bradykinesia, rigidity and tremor.

The Chu Lab integrates molecular, cellular and systems neuroscience to identify mechanisms that contribute to progressive degeneration of midbrain dopaminergic neurons, and abnormal circuit activity that underlies the devastating motor symptoms of Parkinson’s disease. The long-term goal of the Chu Lab is to develop precision strategies to target specific types of neurons or neural circuits for disease prevention and treatment.

PubMed | Google Scholar

Chen L, Daniels S, Dvorak R, Chu H-Y. 2023. Reduced thalamic excitation to motor cortical pyramidal tract neurons in parkinsonism. Sci Adv 9(34).

Chen L, Nagaraja C, Daniels S, Fisk ZA, Dvorak R, Meyerdirk L, Steiner JA, Escobar Galvis ML, Henderson MX, Rousseaux MWC, Brundin P, Chu HY. 2022. Synaptic location is a determinant of the detrimental effects of α-synuclein pathology to glutamatergic transmission in the basolateral amygdala. eLife 11:e78055.

Chen L, Daniels S, Kim Y, Chu HY. 2021. Cell type-specific decrease of the intrinsic excitability of motor cortical pyramidal neurons in Parkinsonism. J Neurosci 41(25):5553–5565.

Chu HY. 2020. Synaptic and cellular plasticity in Parkinson’s disease. Acta Pharmacol Sin 41(4):447–452.

McIver EL, Atherton JF, Chu HY, Cosgrove KE, Kondapalli J, Wokosin D, Surmeier DJ, Bevan MD. 2019. Maladaptive downregulation of autonomous subthalamic nucleus activity following loss of midbrain dopamine neurons. Cell Rep 28(4): 992–1002.e4.

Chu HY, McIver EL, Kovaleski RF, Atherton JF, Bevan MD. 2017. Loss of hyperdirect pathway cortico-subthalamic inputs following degeneration of midbrain dopamine neurons. Neuron 95(6):1306–1318.
*Comment in Neuron

Chu HY, Atherton JF, Wokosin D, Surmeier DJ, Bevan MD. 2015. Heterosynaptic regulation of external globus pallidus inputs to the subthalamic nucleus by motor cortex. Neuron 85(2):364–376.
*Comment in Neuron

Chu HY, Li J, Ito W, Li J, Morozov A. 2012. Target-specific suppression of GABA release from parvalbumin-interneurons in basolateral amygdala by dopamine. J Neurosci 32(42):14815–14820.
*Comment in F1000Prime.com/717963921#eval793465677

Zhou S, Chu HY, Jin GZ, Cui JM, Zhen X. 2014. Effects of SKF83959 on the excitability of hippocampal CA1 pyramidal neurons: a modeling study. Acta Pharmacol Sin 35(6):738–751.

Gao M*, Chu HY*, Jin GZ, Zhang ZJ, Wu J, Zhen X. 2011. l-Stepholidine-induced excitation of dopamine neurons in rat ventral tegmental area is associated with its 5-HT1A receptor partial agonistic activity. Synapse 65(5):379–387.
*Co-first authors

Chu HY, Wu Q, Zhou S, Cao X, Zhang A, Jin GZ, Hu GY, Zhen X. 2011. SKF83959 suppresses excitatory synaptic transmission in rat hippocampus via a dopamine receptor-independent mechanism. J Neurosci Res 89(8):1259–1266.

Chu HY, Gu Q, Jin GZ, Hu GY, Zhen X. 2010. Electrophysiological effects of SKF83959 on hippocampal CA1 pyramidal neurons: Potential mechanisms for the drug’s neuroprotective effects. PLoS One.

Chu HY, Yang Z, Zhao B, Jin GZ, Hu GY, Zhen X. 2010. Activation of phosphatidylinositol-linked D1-like receptors increases spontaneous glutamate release in rat somatosensory cortical neurons in vitro. Brain Res 1343:20–27.

Chu HY, Zhen X. 2010. Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels in the regulation of midbrain dopamine systems. Acta Pharmacol Sin 31(9):1036–1043.