I obtained my PhD in Neuroscience from the University of California, San Diego in 2013. In my doctoral research, I identified a molecular mechanism that governs the formation of specific classes of hippocampal synapses. Through this work, I gained experience in slice electrophysiology, molecular biology, and in vivo molecular manipulations.
I joined the Luo lab at Stanford as a postdoc in 2013. I first examined region- and layer-specific patterns of cortical synaptic connectivity using viral-genetic tools developed in the Luo lab. I am currently using state-of-the art genetic tools, including a knockin mouse that I developed to access activated neurons (TRAP2), to investigate the role of prefrontal cortex in remote fear memory retrieval. Through this work, I am uncovering the circuit mechanisms that underlie behaviors which become maladaptive in psychiatric disorders.
Honors & Awards
Allison J. Doupe Fellowship, McKnight Endowment Fund (2017)
NIH Ruth L. Kirchstein National Research Service Award (F32), National Institute of Neurological Disorders and Stroke (2014–2016)
T32 Epilepsy Postdoctoral Training Grant Recipient, Stanford University (2013–2014)
Departmental Honors, UC Berkeley (2007)
Undergraduate Research Apprentice Program Summer Research Award, UC Berkeley (2007)
Bachelor of Arts, University of California Berkeley (2007)
Doctor of Philosophy, University of California San Diego (2013)
Liqun Luo, Postdoctoral Faculty Sponsor
Genetic strategies to access activated neurons.
Current opinion in neurobiology
2017; 45: 121-129
A major goal of modern neuroscience is to understand how ensembles of neurons participate in neural circuits underlying behavior. The recent explosion of genetically-encoded circuit analysis tools has allowed neuroscientists to characterize molecularly-defined neuronal types with unprecedented detail. However, since neurons defined by molecular expression can be functionally heterogeneous, targeting circuit analysis tools to neurons based on their activity is critical to elucidating the neural basis of behavior. Here we review genetic strategies to access activated neurons and characterize their functional properties, molecular profiles, connectivity, and causal roles in sensory-coding, memory, and valence-encoding. We also discuss future possibilities for improving these strategies and using them to screen brain-wide activity patterns underlying adaptive and maladaptive behaviors.
View details for DOI 10.1016/j.conb.2017.05.014
View details for PubMedID 28577429
- Thirst-Associated Preoptic Neurons Encode an Aversive Motivational Drive Science (in press) 2017
Amyloid Accumulation Drives Proteome-wide Alterations in Mouse Models of Alzheimer's Disease-like Pathology.
2017; 21 (9): 2614–27
Amyloid beta (Aβ) peptides impair multiple cellular pathways and play a causative role in Alzheimer's disease (AD) pathology, but how the brain proteome is remodeled by this process is unknown. To identify protein networks associated with AD-like pathology, we performed global quantitative proteomic analysis in three mouse models at young and old ages. Our analysis revealed a robust increase in Apolipoprotein E (ApoE) levels in nearly all brain regions with increased Aβ levels. Taken together with prior findings on ApoE driving Aβ accumulation, this analysis points to a pathological dysregulation of the ApoE-Aβ axis. We also found dysregulation of protein networks involved in excitatory synaptic transmission. Analysis of the AMPA receptor (AMPAR) complex revealed specific loss of TARPγ-2, a key AMPAR-trafficking protein. Expression of TARPγ-2 in hAPP transgenic mice restored AMPA currents. This proteomic database represents a resource for the identification of protein alterations responsible for AD.
View details for DOI 10.1016/j.celrep.2017.11.009
View details for PubMedID 29186695
View details for PubMedCentralID PMC5726791
- Connectivity of mouse somatosensory and prefrontal cortex examined with trans-synaptic tracing. Nature neuroscience 2015; 18 (11): 1687-1697
The Sorting Receptor SorCS1 Regulates Trafficking of Neurexin and AMPA Receptors
2015; 87 (4): 764-780
The formation, function, and plasticity of synapses require dynamic changes in synaptic receptor composition. Here, we identify the sorting receptor SorCS1 as a key regulator of synaptic receptor trafficking. Four independent proteomic analyses identify the synaptic adhesion molecule neurexin and the AMPA glutamate receptor (AMPAR) as major proteins sorted by SorCS1. SorCS1 localizes to early and recycling endosomes and regulates neurexin and AMPAR surface trafficking. Surface proteome analysis of SorCS1-deficient neurons shows decreased surface levels of these, and additional, receptors. Quantitative in vivo analysis of SorCS1-knockout synaptic proteomes identifies SorCS1 as a global trafficking regulator and reveals decreased levels of receptors regulating adhesion and neurotransmission, including neurexins and AMPARs. Consequently, glutamatergic transmission at SorCS1-deficient synapses is reduced due to impaired AMPAR surface expression. SORCS1 mutations have been associated with autism and Alzheimer disease, suggesting that perturbed receptor trafficking contributes to synaptic-composition and -function defects underlying synaptopathies.
View details for DOI 10.1016/j.neuron.2015.08.007
View details for Web of Science ID 000361145600010
View details for PubMedID 26291160
View details for PubMedCentralID PMC4692362
NGL-2 Regulates Input-Specific Synapse Development in CA1 Pyramidal Neurons
2012; 76 (4): 762-775
An important organizing feature of the CNS is that individual neurons receive input from many different sources. Independent regulation of synaptic input is critical for the function and adaptive responses of the nervous system, but the underlying molecular mechanisms are not well understood. We identify the leucine-rich repeat (LRR)-containing protein NGL-2 (Lrrc4) as a key regulator of input-specific synapse development in the hippocampus. Using genetic deletion and shRNA-mediated knockdown, we demonstrate a role for NGL-2 in regulating the strength of synaptic transmission and spine density specifically at Schaffer collateral synapses in the stratum radiatum (SR) in CA1. NGL-2 protein is restricted to SR and spine regulation requires NGL-2's LRR and PDZ-binding domains. Finally, loss of NGL-2 disrupts cooperative interactions between distal and proximal synapses in CA1 pyramidal cells. These results demonstrate that NGL-2 is critical for pathway-specific synapse development and functional integration of distinct inputs.
View details for DOI 10.1016/j.neuron.2012.10.013
View details for Web of Science ID 000311977900010
View details for PubMedID 23177961
NeuroD2 regulates the development of hippocampal mossy fiber synapses
The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF) synapse.Using NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice.These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo.
View details for DOI 10.1186/1749-8104-7-9
View details for Web of Science ID 000302228000001
View details for PubMedID 22369234
View details for PubMedCentralID PMC3310804