Chan, Savio C., PhD

Selected Publications

Selected Publications

Original Investigations
Abrahao KP, Chancey JH, Chan CS, Lovinger DM. (2017). Ethanol-Sensitive Pacemaker Neurons in the External Globus Pallidus. Neuropsychopharmacol. 42(5):1070-1081.
Sebel LE, Graves SM, Chan CS, Surmeier DJ. (2017). Subchronic haloperidol induced adaptations in striatal projection neurons. Neuropsychopharmacol. 42(4):963-973.
Cui Q, Pitt JE*, Pamukcu A*, Poulin JF, Kelver DA, Fiske MP, Kennedy RT, Mabrouk OS, Awatramani R, Chan CS. (2017). Astrocytic Gating of Striatopallidal Transmission is Disrupted in Parkinsonian Mice. Cell Reports. 17: 2431–2444
Glajch KE, Kelver DA, Hegeman DJ, Cui Q, Hernández VM, Xenias HS, Huang TY, Justice NJ, Chan CS. (2016). Npas1+ Pallidal Neurons Target Striatal Projection Neurons. J Neurosci. 36(20):5472–5488.
Hernández VM, Hegeman DJ, Cui Q, Kelver DA, Fiske MP, Glajch KE, Huang TY, Justice NJ, Chan CS. (2015). Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus. J Neurosci. 35(34):11830 –11847.
Neuner S, Hoffmann B, Chong JA, Abramowitz J, Birnbaumer L, Tryba KA, Greene A, Chan CS, Kaczorowski CC. (2015).TrpC3 Channels Critically Shape Spatial Memory Formation. Behav Brain Res. 281C:69-77.
Chávez AE, Hernández VM, Rodenas-Ruano A, Chan CS, Castillo P. (2014). Compartment-specific modulation of GABAergic synaptic transmission by TRPV1 channels in the dentate gyrus. J Neurosci. 34(50):16621-16629.
Fieblinger T, Graves SM, Sebel L, Alacer C, Plotkin JL, Gertler TS, Chan CS, Heiman M, Greengard P, Cenci MA, Surmeier DJ. (2015). Cell type-specific Plasticity of Striatal Projection Neurons in Parkinsonism and l-Dopa-induced Dyskinesia. Nat Commun. 5:5316.
Plotkin JL, Day M, Peterson JD, Xie Z, Kress G, Rafalovich I, Gertler TS, Flajolet M, Greengard P, Stavarache M, Kaplitt MG, Chan CS, Surmeier DJ. (2014). Impaired TrkB Signaling Underlies Corticostriatal Dysfunction in Huntington’s Disease. Neuron. 83(1):178-188.
Plotkin J, Shen W, Rafalovich I, Sebel L, Day M, Chan CS, Surmeier DJ. (2013). Regulation of Striatal Synaptic Plasticity by Dendritic Calcium Release. J Neurophysiol. 110:2325-2336.
Fan K, Baufreton J, Surmeier DJ, Chan CS, Bevan MD. (2012). Proliferation of Globus Pallidus-Subthalamic Nucleus Synapses Following Degeneration of Midbrain Dopamine Neurons. J Neurosci. 32(40):13718-13728.
Chan CS, Peterson JD, Gertler TS, Glajch KE, Quintana RE, Cui QL, Sebel LE, Plotkin J, Shen W, Heiman M, Heintz N, Greengard P, Surmeier DJ. (2012). Strain-Specific Regulation of Striatal Phenotype in Drd2-eGFP BAC Trasgenic Mice. J Neurosci. 32(27):9124 –9132.
Sheet PL, Suter BA, Kiritani K, Chan CS, Surmeier DJ, Shepherd GM. (2011). Corticospinal-specific HCN expression in mouse motor cortex: Ih-dependent synaptic integration as a candidate microcircuit mechanism involved in motor control. J Neurophysiol. 106(5):2216–2231.
Chan CS, Glajch KE, Gertler TS, Guzman JN, Mercer JN, Lewis AS, Goldberg AB, Shigemoto R, Fleming SM, Chetkovich DM, Osten P, Kita H. Surmeier DJ. (2011). HCN Channelopathy in External Globus Pallidus Neurons in Models of Parkinson’s Disease. Nat Neurosci. 14(1):86–92.
Guzman JN, Sánchez-Padilla J, Chan CS, Surmeier DJ. (2009). Robust Pacemaking in Dopaminergic Neurons. J Neurosci. 29(35):11011–11019.
Deister CA, Chan CS, Surmeier DJ, Wilson CJ. (2009). SK Channels Regulate Spike Time Precision Through Cooperative Interactions with Voltage-Gated Ion Channels. J Neurosci. 29(26):8452–8461.
Lewis AS, Schwartz E, Chan CS, Noam Y, Shin M, Wadman WJ, Surmeier, DJ, Baram TZ, Macdonald RL, Chetkovich DM. (2009). Alternatively spliced isoforms of TRIP8b differentially control h channel trafficking and function. J Neurosci. 29(19):6250–65.
Wu WW*, Chan CS*, Surmeier DJ, Disterhoft JF. (2008). Coupling of L-Type Ca2+ Channels to Kv7/KCNQ Channels Creates a Novel, Activity-Dependent, Homeostatic Intrinsic Plasticity. J Neurophysiol. 100(4):1897–1908. (*equal contribution)
Gertler TS, Chan CS, Surmeier DJ. (2008). Dichotomous Anatomical Properties of Adult Striatal Medium Spiny Neurons. J Neurosci.28(43):10814–10824.
Mercer JN, Chan CS, Tkatch T, Held J, Surmeier DJ. (2007). Nav1.6 sodium channels are critical to pacemaking and fast-spiking in globus pallidus neurons. J Neurosci. 27(49):13552–66.
Chan CS, Guzman JN, Illijic E, Mercer JN, Rick CE, Tkatch T, Meredith GE, Surmeier DJ. (2007). ‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease. Nature. 447(7148):1081–6.
Mercer J, Chan CS, Hernandez-Lopez S, Held J, Tkatch T, Surmeier DJ. (2004). D2 dopamine receptor-mediated modulation of voltage-dependent Na+ channels reduces autonomous activity in striatal cholinergic interneurons. J Neurosci. 24(46):10289–301.
Chan CS, Shigemoto R, Mercer JN, Surmeier DJ. (2004). HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons. J Neurosci. 24(44):9921-32.
Wu WW, Chan CS, Disterhoft JF. (2004). The slow afterhyperpolarization governs the development of NMDA receptor-dependent afterdepolarization in CA1 pyramidal neurons during synaptic stimulation. J Neurophysiol. 92(4):2346–56.
Chen L, Chan CS, Yung WH. (2004). Electrophysiological and behavioral effects of zolpidem in rat globus pallidus. Exp Neurol. 186(2):212–20.
Chen L, Chan CS, Yung WH. (2002). Rotational behavior and electrophysiological effects induced by GABA(B) receptor activation in rat globus pallidus. Neuroscience. 114(2):417–725.
Yung WH, Leung PS, NG SS. Zhang J, Chan CS, Chow BK. (2001). Secretin facilitates GABA transmission in the cerebellum. J Neurosci. 21(18):7063–7068.
Chan PK, Chan CS, Yung WH. (1998). Presynaptic inhibition of GABAergic inputs to rat substantia nigra pars reticulata neurons by cannabinoid agonist. NeuroReport. 9:671–675.
Reviews and Commentary
Hegeman DJ, Hong ES, Hernández VM, Chan CS (2016). The External Globus Pallidus: Progress and Perspectives. Eur J Neurosci. 43(10):1239–1265.
Gittis AH, Berke JD, Bevan MD, Chan CS, Mallet N, Morrow MM, Schmidt R (2014). New Roles for the External Globus Pallidus in Basal Ganglia Circuits and Behavior. J Neurosci. 34(46):15178-8.
Chan CS, Surmeier DJ. (2014). Astrocytes go awry in Huntington’s disease. Nat Neurosci. 17(5):641–642.
Surmeier DJ, Shen W, Day M, Gertler TS, Chan
CS, Tian X, Plotkin J. (2010). The role of dopamine in modulating the structure and function of striatal circuits. Prog Brain Res. 183C:148–167.
Chan CS*, Gertler TS*, Surmeier DJ. (2010). A Molecular Basis for the Increased Vulnerability of Substantia Nigra Dopamine Neurons in Aging and Parkinson’s Disease. Movement Disorders. 25(Suppl. 1):S63–S70. (*equal contribution)
Chan CS*, Gertler TS*, Surmeier DJ. (2009). Calcium homeostasis in dopamine neurons and Parkinson’s disease. Trends Neursoci. 32(5):249–256. (*equal contribution)
Surmeier DJ, Mercer JN, Chan CS. (2005). Autonomous pacemaker in the basal ganglia: Who needs excitatory synapses anyway? Curr Opin Neurobiol. 15(3)312–318.
Chan CS, Surmeier DJ, Yung WH. (2005). Striatal information processing in globus pallidus: timing matters. NeuroSignals. 14(6): 281–9.
Books and Book Chapters
Surmeier DJ, Shen W, Gertler TS, Chan CS. (2011). Dopaminergic Modulation of Glutamatergic Synaptic Plasticity in Striatal Circuits: New Insights from BAC-Transgenic Mice. In “Dopamine-Glutamate Interactions in the Basal Ganglia” Ed. Susan S.
Surmeier DJ, Day M, Gertler TS, Chan CS, Shen W. (2010). D1 and D2 Dopamine Receptor Modulation of Glutamatergic Signaling in Striatal Medium Spiny Neurons. In: “Handbook of Basal Ganglia, 1st Edition” Ed. Steiner H, Tseng KY. p113-132.
Surmeier DJ, Day M, Gertler TS, Chan CS, Shen W. (2009). Dopaminergic modulation of striatal glutamatergic signaling in health and Parkinson’s disease. In: “Dopamine Handbook” Ed. Iversen L, Iversen S, Dunnett S and Björklund A. p349–467.

Information

Name

Chan, Savio C., PhD

Title

Assistant Professor

Email

saviochan@northwestern.edu

Office Phone

312-503-1146 (lab) 312-503-4153 (office)

Office Fax

312-503-5101

Department

Physiology

Office

Robert H Lurie Medical Research Center Room 8-220 (lab) Room 8-113 (office)

Website

https://www.saviochanlab.org/

Areas of Research

Mechanisms of Drug Action, Molecular Neuroscience, Motor Control, Neurobiology of Disease, Signal Transduction

NU Scholar Profile

http://www.scholars.northwestern.edu/expert.asp?u_id=334

Recent Publications on PubMed

https://www.ncbi.nlm.nih.gov/myncbi/browse/collection/40455366/?sort=date&direction=descending

Current Research

Current Research

Cellular diversity

Phasic changes in neuronal activity of the external globus pallidus (GPe) are observed with movements. In contrast, the activity of GPe neurons precipitates into synchronous rhythmic bursting in animal models and patients of Parkinson’s disease (PD). Despite the imminent behavioral and disease relevance of the GPe, its cellular makeup and heterogeneity have not been fully appreciated nor investigated. In the past few years, our laboratory has addressed this knowledge gap by identifying two principal GPe neuron classes, which can be distinguished by their non-overlapping expression of the molecular markers parvalbumin and Npas1. Furthermore, our group has demonstrated that parvalbumin neurons and Npas1 neurons have distinct cellular and circuit properties; yet, compelling data from our group and others suggest the existence of an additional principal class that accounts for up to 15–20% of the total GPe neuron population. By utilizing a multidisciplinary approach, our goal is to define this neuron class in the GPe by its birthplace, lineage identity, genetic profile, electrophysiological signature, axonal projection, excitatory inputs, and behavioral relevance. Our research challenges the prevailing circuit model and will add to the knowledge of the long-understudied GPe and its alterations with PD. The successful achievement of these aims will define the role of the GPe in behavioral and disease contexts.

Neurodegenerative diseases

To date, millions of people in the US suffer from neurodegenerative diseases. Current therapeutic strategies are limited, short-lived, and ineffective. Our research seeks to provide the mechanisms that underlie the pathogenesis of Alzheimer's Disease, Parkinson’s disease, and Huntington’s Disease. We hope to translate our insights into developing novel treatments for these neurological disorders.

Alzheimer's disease is the most common neurodegenerative disease and it is the most common underlying cause of dementia. It affects primarily the cortex and hippocampus. Severe synapse loss and inclusions can be observed. Our research seek to delineate the cellular processes that lead to the network dysfunction and the endogenous clearing mechanism of oligomers.

Parkinson’s disease and Huntington’s disease are the two major neurodegenerative diseases that affect the motor function. Our research interests center on better understanding the cellular and molecular building blocks that make up the basal ganglia macrocircuit as well as their implications in both health and disease.

Inter-cell communications

An effective communication in the brain involves proper controls of how signals are generated, how they are terminated, and how they are spatiotemporally distributed. This process involves a complex architecture of ion channels, receptors, synapse, release and clearance machinery, etc. Our lab studies how this is achieved and how it is altered in disease conditions. The main focus is on intrinsic excitability, neurotransmission, and their regulation by astrocytes.

Other ongoing research

Stress-anxiety driven motor behavior, astrocyte physiology, dystonia, and Alzheimer’s disease.