Academic Appointments


All Publications


  • Love or not? A new subpopulation of neurons controls the switch of female sexual behavior. Neuron Liu, Z., Cao, P. 2022; 110 (18): 2893-2895

    Abstract

    In this issue of Neuron, Yin and colleagues describe a new subpopulation of neurons in the ventrolateral part of the ventromedial hypothalamus, cholecystokinin A receptor (Cckar)-expressing cells, and unravel their roles in regulating female sexual behavior over reproductive cycles.

    View details for DOI 10.1016/j.neuron.2022.08.008

    View details for PubMedID 36137518

  • Calsyntenin-3, an atypical cadherin, suppresses inhibitory synapses but increases excitatory parallel-fiber synapses in cerebellum. eLife Liu, Z., Jiang, M., Liakath-Ali, K., Sclip, A., Ko, J., Zhang, R. S., Sudhof, T. C. 2022; 11

    Abstract

    Cadherins contribute to the organization of nearly all tissues, but the functions of several evolutionarily conserved cadherins, including those of calsyntenins, remain enigmatic. Puzzlingly, two distinct, non-overlapping functions for calsyntenins were proposed: As postsynaptic neurexin ligands in synapse formation, or as presynaptic kinesin adaptors in vesicular transport. Here, we show that, surprisingly, acute CRISPR-mediated deletion of calsyntenin-3 in mouse cerebellum in vivo causes a large decrease in inhibitory synapse, but a robust increase in excitatory parallel-fiber synapses in Purkinje cells. As a result, inhibitory synaptic transmission was suppressed, whereas parallel-fiber synaptic transmission was enhanced in Purkinje cells by the calsyntenin-3 deletion. No changes in the dendritic architecture of Purkinje cells or in climbing-fiber synapses were detected. Sparse selective deletion of calsyntenin-3 only in Purkinje cells recapitulated the synaptic phenotype, indicating that calsyntenin-3 acts by a cell-autonomous postsynaptic mechanism in cerebellum. Thus, by promoting formation of excitatory parallel-fiber synapses and decreasing formation of inhibitory synapses in the same neuron, calsyntenin-3 functions as a postsynaptic adhesion molecule that regulates the excitatory/inhibitory balance in Purkinje cells.

    View details for DOI 10.7554/eLife.70664

    View details for PubMedID 35420982

  • A Synaptic Circuit Required for Acquisition but Not Recall of Social Transmission of Food Preference. Neuron Wang, C. Y., Liu, Z. n., Ng, Y. H., Südhof, T. C. 2020

    Abstract

    During social transmission of food preference (STFP), the combination of an olfactory sensory input with a social cue induces long-term memory of a food odor. How a social cue produces long-term learning of an olfactory input, however, remains unknown. Here we show that the neurons of the anterior olfactory nucleus (AON), which form abundant synaptic projections onto granule cells in the olfactory bulb (OB), express the synaptogenic molecule C1ql3. Deletion of C1ql3 in the dorsolateral AON impaired synaptic AON→OB connections and abolished acquisition, but not recall, of STFP memory without significantly affecting basal olfaction. Moreover, deletion in granule cells of the OB of Bai3, a postsynaptic GPCR that binds C1ql3, similarly suppressed synaptic transmission at AON→OB projections and abolished acquisition, but not recall, of STFP memory. Thus, synaptic AON→OB connections are selectively required for STFP memory acquisition and are formed by an essential interaction of presynaptic C1ql3 with postsynaptic Bai3.

    View details for DOI 10.1016/j.neuron.2020.04.004

    View details for PubMedID 32369733

  • Synaptic neurexin-1 assembles into dynamically regulated active zone nanoclusters. The Journal of cell biology Trotter, J. H., Hao, J., Maxeiner, S., Tsetsenis, T., Liu, Z., Zhuang, X., Sudhof, T. C. 2019

    Abstract

    Neurexins are well-characterized presynaptic cell adhesion molecules that engage multifarious postsynaptic ligands and organize diverse synapse properties. However, the precise synaptic localization of neurexins remains enigmatic. Using super-resolution microscopy, we demonstrate that neurexin-1 forms discrete nanoclusters at excitatory synapses, revealing a novel organizational feature of synaptic architecture. Synapses generally contain a single nanocluster that comprises more than four neurexin-1 molecules and that also includes neurexin-2 and/or neurexin-3 isoforms. Moreover, we find that neurexin-1 is physiologically cleaved by ADAM10 similar to its ligand neuroligin-1, with 4-6% of neurexin-1 and 2-3% of neuroligin-1 present in the adult brain as soluble ectodomain proteins. Blocking ADAM10-mediated neurexin-1 cleavage dramatically increased the synaptic neurexin-1 content, thereby elevating the percentage of Homer1(+) excitatory synapses containing neurexin-1 nanoclusters from 40-50% to 80%, and doubling the number of neurexin-1 molecules per nanocluster. Taken together, our results reveal an unexpected nanodomain organization of synapses in which neurexin-1 is assembled into discrete presynaptic nanoclusters that are dynamically regulated via ectodomain cleavage.

    View details for DOI 10.1083/jcb.201812076

    View details for PubMedID 31262725

  • A central amygdala to zona incerta projection is required for acquisition and remote recall of conditioned fear memory NATURE NEUROSCIENCE Zhou, M., Liu, Z., Melin, M. D., Ng, Y., Xu, W., Sudhof, T. C. 2018; 21 (11): 1515-+
  • A central amygdala to zona incerta projection is required for acquisition and remote recall of conditioned fear memory. Nature neuroscience Zhou, M., Liu, Z., Melin, M. D., Ng, Y. H., Xu, W., Sudhof, T. C. 2018

    Abstract

    The formation and retrieval of conditioned fear memories critically depend on the amygdala. Here we identify an inhibitory projection from somatostatin-positive neurons in the central amygdala to parvalbumin-positive neurons in the zona incerta that is required for both recent and remote fear memories. Thus, the amygdala inhibitory input to parvalbumin-positive neurons in the zona incerta, a nucleus not previously implicated in fear memory, is an essential component of the fear memory circuitry.

    View details for PubMedID 30349111

  • IGF1-Dependent Synaptic Plasticity of Mitral Cells in Olfactory Memory during Social Learning NEURON Liu, Z., Chen, Z., Shang, C., Yan, F., Shi, Y., Zhang, J., Qu, B., Han, H., Wang, Y., Li, D., Udhof, T. S., Cao, P. 2017; 95 (1): 106-+

    Abstract

    During social transmission of food preference (STFP), mice form long-term memory of food odors presented by a social partner. How does the brain associate a social context with odor signals to promote memory encoding? Here we show that odor exposure during STFP, but not unconditioned odor exposure, induces glomerulus-specific long-term potentiation (LTP) of synaptic strength selectively at the GABAergic component of dendrodendritic synapses of granule and mitral cells in the olfactory bulb. Conditional deletion of synaptotagmin-10, the Ca2+ sensor for IGF1 secretion from mitral cells, or deletion of IGF1 receptor in the olfactory bulb prevented the socially relevant GABAergic LTP and impaired memory formation after STFP. Conversely, the addition of IGF1 to acute olfactory bulb slices elicited the GABAergic LTP in mitral cells by enhancing postsynaptic GABA receptor responses. Thus, our data reveal a synaptic substrate for a socially conditioned long-term memory that operates at the level of the initial processing of sensory information.

    View details for PubMedID 28683263