All Publications

  • Subicular neurons encode concave and convex geometries. Nature Sun, Y., Nitz, D. A., Xu, X., Giocomo, L. M. 2024


    Animals in the natural world constantly encounter geometrically complex landscapes. Successful navigation requiresthat they understand geometric features of these landscapes, including boundaries, landmarks, corners and curved areas, all of which collectively define the geometry of the environment1-12. Crucial to the reconstruction of the geometric layout of natural environments are concave and convex features, such as corners and protrusions. However, the neural substrates that could underlie the perception of concavity and convexity in the environment remain elusive. Here we show that the dorsal subiculum contains neurons that encode corners across environmental geometries in an allocentric reference frame. Using longitudinal calcium imaging in freely behaving mice, we find that corner cells tune their activity to reflect the geometric properties of corners, including corner angles, wall height and the degree of wall intersection. A separate population of subicular neurons encode convex corners of both larger environments and discrete objects. Both corner cells are non-overlapping with the population of subicular neurons that encode environmental boundaries. Furthermore, corner cells that encode concave or convex corners generalize their activity such that they respond, respectively, to concave or convex curvatures within an environment. Together, our findings suggest that the subiculum contains the geometric information needed to reconstruct the shape and layout of naturalistic spatial environments.

    View details for DOI 10.1038/s41586-024-07139-z

    View details for PubMedID 38448584

  • Ketamine evoked disruption of entorhinal and hippocampal spatial maps. Nature communications Masuda, F. K., Aery Jones, E. A., Sun, Y., Giocomo, L. M. 2023; 14 (1): 6285


    Ketamine, a rapid-acting anesthetic and acute antidepressant, carries undesirable spatial cognition side effects including out-of-body experiences and spatial memory impairments. The neural substrates that underlie these alterations in spatial cognition however, remain incompletely understood. Here, we used electrophysiology and calcium imaging to examine ketamine's impacts on the medial entorhinal cortex and hippocampus, which contain neurons that encode an animal's spatial position, as mice navigated virtual reality and real world environments. Ketamine acutely increased firing rates, degraded cell-pair temporal firing-rate relationships, and altered oscillations, leading to longer-term remapping of spatial representations. In the reciprocally connected hippocampus, the activity of neurons that encode the position of the animal was suppressed after ketamine administration. Together, these findings demonstrate ketamine-induced dysfunction of the MEC-hippocampal circuit at the single cell, local-circuit population, and network levels, connecting previously demonstrated physiological effects of ketamine on spatial cognition to alterations in the spatial navigation circuit.

    View details for DOI 10.1038/s41467-023-41750-4

    View details for PubMedID 37805575

    View details for PubMedCentralID PMC10560293

  • Anatomical and molecular characterization of parvalbumin-cholecystokinin co-expressing inhibitory interneurons: implications for neuropsychiatric conditions. Molecular psychiatry Grieco, S. F., Johnston, K. G., Gao, P., Garduno, B. M., Tang, B., Yi, E., Sun, Y., Horwitz, G. D., Yu, Z., Holmes, T. C., Xu, X. 2023


    Inhibitory interneurons are crucial to brain function and their dysfunction is implicated in neuropsychiatric conditions. Emerging evidence indicates that cholecystokinin (CCK)-expressing interneurons (CCK+) are highly heterogenous. We find that a large subset of parvalbumin-expressing (PV+) interneurons express CCK strongly;between 40 and 56% of PV+ interneurons in mouse hippocampal CA1express CCK. Primate interneurons also exhibit substantial PV/CCK co-expression. Mouse PV+/CCK+ and PV+/CCK- cells show distinguishable electrophysiological and molecular characteristics. Analysis of single nuclei RNA-seq and ATAC-seq data shows that PV+/CCK+ cells are a subset of PV+ cells, not of synuclein gamma positive (SNCG+) cells, and that they strongly express oxidative phosphorylation (OXPHOS) genes. We find that mitochondrial complex I and IV-associated OXPHOS gene expression isstrongly correlated with CCK expression in PV+ interneurons at both the transcriptomic and protein levels. Both PV+ interneurons and dysregulation of OXPHOS processes are implicated in neuropsychiatric conditions, including autism spectrum (ASD) disorder and schizophrenia(SCZ). Analysis of human brain samples from patients with these conditions shows alterations in OXPHOS gene expression. Together these data reveal important molecular characteristics of PV-CCK co-expressing interneurons and support their implication in neuropsychiatric conditions.

    View details for DOI 10.1038/s41380-023-02153-5

    View details for PubMedID 37443194

  • Whole-brain input mapping of the lateral versus medial anterodorsal bed nucleus of the stria terminalis in the mouse. Neurobiology of stress Sun, Y., Zweifel, L. S., Holmes, T. C., Xu, X. 2023; 23: 100527


    The anterior portion of the bed nucleus of the stria terminalis (BNST) modulates fear and stress responses. The anterodorsal BNST (adBNST) can be anatomically subdivided further into the lateral and medial divisions. Although output projections of BNST subregions have been studied, the local and global input connections to these subregions remain poorly understood. To further understand BNST-centered circuit operations, we have applied new viral-genetic tracing and functional circuit mapping to determine detailed synaptic circuit inputs to lateral and medial subregions of adBNST in the mouse. Monosynaptic canine adenovirus type 2 (CAV2) and rabies virus-based retrograde tracers were injected in the adBNST subregions. The amygdalar complex, hypothalamus and hippocampal formation account for the majority of overall inputs to adBNST. However, lateral versus medial adBNST subregions have distinct patterns of long-range cortical and limbic brain inputs. The lateral adBNST has more input connections from prefrontal (prelimbic, infralimbic, cingulate) and insular cortices, anterior thalamus and ectorhinal/perirhinal cortices. In contrast, the medial adBNST received biased inputs from the medial amygdala, lateral septum, hypothalamus nuclei and ventral subiculum. We confirmed long-range functional inputs from the amydalohippocampal area and basolateral amygdala to the adBNST using ChR2-assisted circuit mapping. Selected novel BNST inputs are also validated with the AAV axonal tracing data from the Allen Institute Mouse Brain Connectivity Atlas. Together, these results provide a comprehensive map of the differential afferent inputs to lateral and medial adBNST subregions, and offer new insight into the functional operations of BNST circuitry for stress and anxiety-related behaviors.

    View details for DOI 10.1016/j.ynstr.2023.100527

    View details for PubMedID 36861029

  • All-optical physiology resolves a synaptic basis for behavioral timescale plasticity. Cell Fan, L. Z., Kim, D. K., Jennings, J. H., Tian, H., Wang, P. Y., Ramakrishnan, C., Randles, S., Sun, Y., Thadhani, E., Kim, Y. S., Quirin, S., Giocomo, L., Cohen, A. E., Deisseroth, K. 2023


    Learning has been associated with modifications of synaptic and circuit properties, but the precise changes storing information in mammals have remained largely unclear. We combined genetically targeted voltage imaging with targeted optogenetic activation and silencing of pre- and post-synaptic neurons to study the mechanisms underlying hippocampal behavioral timescale plasticity. In mice navigating a virtual-reality environment, targeted optogenetic activation of individual CA1 cells at specific places induced stable representations of these places in the targeted cells. Optical elicitation, recording, and modulation of synaptic transmission in behaving mice revealed that activity in presynaptic CA2/3 cells was required for the induction of plasticity in CA1 and, furthermore, that during induction of these place fields in single CA1 cells, synaptic input from CA2/3 onto these same cells was potentiated. These results reveal synaptic implementation of hippocampal behavioral timescale plasticity and define a methodology to resolve synaptic plasticity during learning and memory in behaving mammals.

    View details for DOI 10.1016/j.cell.2022.12.035

    View details for PubMedID 36669484

  • Neural circuit dynamics of drug-context associative learning in the mouse hippocampus. Nature communications Sun, Y., Giocomo, L. M. 2022; 13 (1): 6721


    The environmental context associated with previous drug consumption is a potent trigger for drug relapse. However, the mechanism by which neural representations of context are modified to incorporate information associated with drugs of abuse remains unknown. Using longitudinal calcium imaging in freely behaving mice, we find that unlike the associative learning of natural reward, drug-context associations for psychostimulants and opioids are encoded in a specific subset of hippocampal neurons. After drug conditioning, these neurons weakened their spatial coding for the non-drug paired context, resulting in an orthogonal representation for the drug versus non-drug context that was predictive of drug-seeking behavior. Furthermore, these neurons were selected based on drug-spatial experience and were exclusively tuned to animals' allocentric position. Together, this work reveals how drugs of abuse alter the hippocampal circuit to encode drug-context associations and points to the possibility of targeting drug-associated memory in the hippocampus.

    View details for DOI 10.1038/s41467-022-34114-x

    View details for PubMedID 36344498

  • CA1-projecting subiculum neurons facilitate object-place learning. Nature neuroscience Sun, Y. n., Jin, S. n., Lin, X. n., Chen, L. n., Qiao, X. n., Jiang, L. n., Zhou, P. n., Johnston, K. G., Golshani, P. n., Nie, Q. n., Holmes, T. C., Nitz, D. A., Xu, X. n. 2019


    Recent anatomical evidence suggests a functionally significant back-projection pathway from the subiculum to the CA1. Here we show that the afferent circuitry of CA1-projecting subicular neurons is biased by inputs from CA1 inhibitory neurons and the visual cortex, but lacks input from the entorhinal cortex. Efferents of the CA1-projecting subiculum neurons also target the perirhinal cortex, an area strongly implicated in object-place learning. We identify a critical role for CA1-projecting subicular neurons in object-location learning and memory, and show that this projection modulates place-specific activity of CA1 neurons and their responses to displaced objects. Together, these experiments reveal a novel pathway by which cortical inputs, particularly those from the visual cortex, reach the hippocampal output region CA1. Our findings also implicate this circuitry in the formation of complex spatial representations and learning of object-place associations.

    View details for DOI 10.1038/s41593-019-0496-y

    View details for PubMedID 31548723

  • Opposing and Complementary Topographic Connectivity Gradients Revealed by Quantitative Analysis of Canonical and Noncanonical Hippocampal CA1 Inputs ENEURO Sun, Y., Nitz, D. A., Holmes, T. C., Xu, X. 2018; 5 (1)


    Physiological studies suggest spatial representation gradients along the CA1 proximodistal axis. To determine the underlying anatomical basis, we quantitatively mapped canonical and noncanonical inputs to excitatory neurons in dorsal hippocampal CA1 along the proximal-distal axis in mice of both sexes using monosynaptic rabies tracing. Our quantitative analyses show comparable strength of subiculum complex and entorhinal cortex (EC) inputs to CA1, significant inputs from presubiculum and parasubiculum to CA1, and a threefold stronger input to proximal versus distal CA1 from CA3. Noncanonical subicular complex inputs exhibit opposing topographic connectivity gradients whereby the subiculum-CA1 input strength systematically increases but the presubiculum-CA1 input strength decreases along the proximal-distal axis. The subiculum input strength cotracks that of the lateral EC, known to be less spatially selective than the medial EC. The functional significance of this organization is verified physiologically for subiculum-to-CA1 inputs. These results reveal a novel anatomical framework by which to determine the circuit bases for CA1 representations.

    View details for DOI 10.1523/ENEURO.0322-17.2018

    View details for Web of Science ID 000429409900034

    View details for PubMedID 29387780

    View details for PubMedCentralID PMC5790753

  • Sexual congruency in the connectome and translatome of VTA dopamine neurons SCIENTIFIC REPORTS Chung, A. S., Miller, S. M., Sun, Y., Xu, X., Zweifel, L. S. 2017; 7: 11120


    The ventral tegmental area (VTA) dopamine system is important for reward, motivation, emotion, learning, and memory. Dysfunctions in the dopamine system are linked to multiple neurological and neuropsychiatric disorders, many of which present with sex differences. Little is known about the extent of heterogeneity in the basic organization of VTA dopamine neurons with regard to sex. Here, we characterized the cell-specific connectivity of VTA dopamine neurons, their mRNA translational profile, and basic electrophysiological characteristics in a common strain of mice. We found no major differences in these metrics, except for differential expression of a Y-chromosome associated mRNA transcript, Eif2s3y, and the X-linked, X-inactivation transcript Xist. Of note, Xist transcript was significantly enriched in dopamine neurons, suggesting tight regulation of X-linked gene expression to ensure sexual congruency. These data indicate that the features that make dopamine neurons unique are highly concordant and not a principal source of sexual dimorphism.

    View details for DOI 10.1038/s41598-017-11478-5

    View details for Web of Science ID 000410063400049

    View details for PubMedID 28894175

    View details for PubMedCentralID PMC5593921

  • Local and Long-Range Circuit Connections to Hilar Mossy Cells in the Dentate Gyrus ENEURO Sun, Y., Grieco, S. F., Holmes, T. C., Xu, X. 2017; 4 (2)


    Hilar mossy cells are the prominent glutamatergic cell type in the dentate hilus of the dentate gyrus (DG); they have been proposed to have critical roles in the DG network. To better understand how mossy cells contribute to DG function, we have applied new viral genetic and functional circuit mapping approaches to quantitatively map and compare local and long-range circuit connections of mossy cells and dentate granule cells in the mouse. The great majority of inputs to mossy cells consist of two parallel inputs from within the DG: an excitatory input pathway from dentate granule cells and an inhibitory input pathway from local DG inhibitory neurons. Mossy cells also receive a moderate degree of excitatory and inhibitory CA3 input from proximal CA3 subfields. Long range inputs to mossy cells are numerically sparse, and they are only identified readily from the medial septum and the septofimbrial nucleus. In comparison, dentate granule cells receive most of their inputs from the entorhinal cortex. The granule cells receive significant synaptic inputs from the hilus and the medial septum, and they also receive direct inputs from both distal and proximal CA3 subfields, which has been underdescribed in the existing literature. Our slice-based physiological mapping studies further supported the identified circuit connections of mossy cells and granule cells. Together, our data suggest that hilar mossy cells are major local circuit integrators and they exert modulation of the activity of dentate granule cells as well as the CA3 region through "back-projection" pathways.

    View details for DOI 10.1523/ENEURO.0097-17.2017

    View details for Web of Science ID 000419523100014

    View details for PubMedID 28451637

    View details for PubMedCentralID PMC5396130

  • Noncanonical Connections Between the Subiculum and Hippocampal CA1 JOURNAL OF COMPARATIVE NEUROLOGY Xu, X., Sun, Y., Holmes, T. C., Lopez, A. J. 2016; 524 (17): 3666–73


    The hippocampal formation is traditionally viewed as having a feedforward, unidirectional circuit organization that promotes propagation of excitatory processes. While the substantial forward projection from hippocampal CA1 to the subiculum has been very well established, accumulating evidence supports the existence of a significant backprojection pathway comprised of both excitatory and inhibitory elements from the subiculum to CA1. Based on these recently updated anatomical connections, such a backprojection could serve to modulate information processing in hippocampal CA1. Here we review the published anatomical and physiological studies on the subiculum to CA1 backprojection, and present recent conclusive anatomical evidence for the presence of noncanonical subicular projections to CA1. New insights into this understudied pathway will improve our understanding of reciprocal CA1-subicular connections and guide future studies on how the subiculum interacts with CA1 to regulate hippocampal circuit activity and learning and memory behaviors. J. Comp. Neurol. 524:3666-3673, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

    View details for DOI 10.1002/cne.24024

    View details for Web of Science ID 000385803400010

    View details for PubMedID 27150503

    View details for PubMedCentralID PMC5050062

  • Neuregulin-1/ErbB4 Signaling Regulates Visual Cortical Plasticity NEURON Sun, Y., Ikrar, T., Davis, M. F., Gong, N., Zheng, X., Luo, Z., Lai, C., Mei, L., Holmes, T. C., Gandhi, S. P., Xu, X. 2016; 92 (1): 160–73


    Experience alters cortical networks through neural plasticity mechanisms. During a developmental critical period, the most dramatic consequence of occluding vision through one eye (monocular deprivation) is a rapid loss of excitatory synaptic inputs to parvalbumin-expressing (PV) inhibitory neurons in visual cortex. Subsequent cortical disinhibition by reduced PV cell activity allows for excitatory ocular dominance plasticity. However, the molecular mechanisms underlying critical period synaptic plasticity are unclear. Here we show that brief monocular deprivation during the critical period downregulates neuregulin-1(NRG1)/ErbB4 signaling in PV neurons, causing retraction of excitatory inputs to PV neurons. Exogenous NRG1 rapidly restores excitatory inputs onto deprived PV cells through downstream PKC-dependent activation and AMPA receptor exocytosis, thus enhancing PV neuronal inhibition to excitatory neurons. NRG1 treatment prevents the loss of deprived eye visual cortical responsiveness in vivo. Our findings reveal molecular, cellular, and circuit mechanisms of NRG1/ErbB4 in regulating the initiation of critical period visual cortical plasticity.

    View details for DOI 10.1016/j.neuron.2016.08.033

    View details for Web of Science ID 000386760700018

    View details for PubMedID 27641496

    View details for PubMedCentralID PMC5310354

  • Differential arousal regulation by prokineticin 2 signaling in the nocturnal mouse and the diurnal monkey MOLECULAR BRAIN Zhou, Q., Burton, K. J., Neal, M. L., Qiao, Y., Kanthasamy, A. G., Sun, Y., Xu, X., Ma, Y., Li, X. 2016; 9: 78


    The temporal organization of activity/rest or sleep/wake rhythms for mammals is regulated by the interaction of light/dark cycle and circadian clocks. The neural and molecular mechanisms that confine the active phase to either day or night period for the diurnal and the nocturnal mammals are unclear. Here we report that prokineticin 2, previously shown as a circadian clock output molecule, is expressed in the intrinsically photosensitive retinal ganglion cells, and the expression of prokineticin 2 in the intrinsically photosensitive retinal ganglion cells is oscillatory in a clock-dependent manner. We further show that the prokineticin 2 signaling is required for the activity and arousal suppression by light in the mouse. Between the nocturnal mouse and the diurnal monkey, a signaling receptor for prokineticin 2 is differentially expressed in the retinorecipient suprachiasmatic nucleus and the superior colliculus, brain projection targets of the intrinsically photosensitive retinal ganglion cells. Blockade with a selective antagonist reveals the respectively inhibitory and stimulatory effect of prokineticin 2 signaling on the arousal levels for the nocturnal mouse and the diurnal monkey. Thus, the mammalian diurnality or nocturnality is likely determined by the differential signaling of prokineticin 2 from the intrinsically photosensitive retinal ganglion cells onto their retinorecipient brain targets.

    View details for DOI 10.1186/s13041-016-0255-x

    View details for Web of Science ID 000381740200001

    View details for PubMedID 27535380

    View details for PubMedCentralID PMC4989352

  • Genetic Cell Targeting Uncovers Specific Neuronal Types and Distinct Subregions in the Bed Nucleus of the Stria Terminalis JOURNAL OF COMPARATIVE NEUROLOGY Nguyen, A. Q., Dela Cruz, J. D., Sun, Y., Holmes, T. C., Xu, X. 2016; 524 (12): 2379–99


    The bed nucleus of the stria terminalis (BNST) plays an important role in fear, stress, and anxiety. It contains a collection of subnuclei delineated by gross cytoarchitecture features; however, there has yet to be a systematic examination of specific BNST neuronal types and their associated neurochemical makeup. The present study focuses on improved characterization of the anterior BNST based on differing molecular and chemical expression aided by mouse genetics. Specific Cre driver lines crossed with a fluorescent reporter line were used for genetic cell targeting and immunochemical staining. Using this new approach, we were able to robustly identify specific excitatory and inhibitory cell types in the BNST. The presence and distribution of excitatory neurons were firmly established; glutamatergic neurons in the anterior BNST accounted for about 14% and 31% of dorsal and ventral BNST cells, respectively. GABAergic neurons expressing different isoforms of glutamic acid decarboxylase were found to have differential subregional distributions. Almost no parvalbumin-expressing cells were found in the BNST, while somatostatin-expressing cells and calretinin-expressing cells account for modest proportions of BNST cells. In addition, vasoactive intestinal peptide-expressing axonal plexuses were prominent in the oval and juxtacapsular subregions. In addition, we discovered that corticotropin-releasing hormone-expressing cells contain GABAergic and glutamatergic subpopulations. Together, this study reveals new information on excitatory and inhibitory neurons in the BNST, which will facilitate genetic dissection and functional studies of BNST subregions. J. Comp. Neurol. 524:2379-2399, 2016. © 2016 Wiley Periodicals, Inc.

    View details for DOI 10.1002/cne.23954

    View details for Web of Science ID 000379967400002

    View details for PubMedID 26718312

    View details for PubMedCentralID PMC5359980

  • High-resolution and cell-type-specific photostimulation mapping shows weak excitatory vs. strong inhibitory inputs in the bed nucleus of the stria terminalis JOURNAL OF NEUROPHYSIOLOGY Xu, X., Ikrar, T., Sun, Y., Santos, R., Holmes, T. C., Francesconi, W., Berton, F. 2016; 115 (6): 3204–16


    The bed nucleus of the stria terminalis (BNST) is a key component of the extended amygdala and has been implicated in anxiety and addiction. As individual neurons function within neural circuits, it is important to understand local microcircuits and larger network connections of identified neuronal types and understand how maladaptive changes in the BNST neural networks are induced by stress and drug abuse. However, due to limitations of classic anatomical and physiological methods, the local circuit organization of synaptic inputs to specific BNST neuron types is not well understood. In this study, we report on the application of high-resolution and cell-type-specific photostimulation methodology developed in our laboratory to local circuit mapping in the BNST. Under calibrated experimental conditions, laser photostimulation via glutamate uncaging or channelrhodopsin-2 photoactivation evokes spiking of BNST neurons perisomatically, without activating spikes from axons of passage or distal dendrites. Whole cell recordings, combined with spatially restricted photostimulation of presynaptic neurons at many different locations over a large region, allow high-resolution mapping of presynaptic input sources to single recorded neurons in the BNST. We constructed maps of synaptic inputs impinging onto corticotrophin-releasing hormone-expressing (CRH+) BNST neurons in the dorsolateral BNST and found that the CRH+ neurons receive predominant local inhibitory synaptic connections with very weak excitatory connections. Through cell-type-specific optogenetic stimulation mapping, we generated maps of somatostatin-expressing neuron-specific inhibitory inputs to BNST neurons. Taken together, the photostimulation-based techniques offer us powerful tools for determining the functional organization of local circuits of specific BNST neuron types.

    View details for DOI 10.1152/jn.01148.2015

    View details for Web of Science ID 000397240600016

    View details for PubMedID 27052587

    View details for PubMedCentralID PMC4946595

  • Cell-Type-Specific Circuit Connectivity of Hippocampal CA1 Revealed through Cre-Dependent Rabies Tracing CELL REPORTS Sun, Y., Nguyen, A. Q., Nguyen, J. P., Le, L., Saur, D., Choi, J., Callaway, E. M., Xu, X. 2014; 7 (1): 269–80


    We developed and applied a Cre-dependent, genetically modified rabies-based tracing system to map direct synaptic connections to specific CA1 neuron types in the mouse hippocampus. We found common inputs to excitatory and inhibitory CA1 neurons from CA3, CA2, the entorhinal cortex (EC), the medial septum (MS), and, unexpectedly, the subiculum. Excitatory CA1 neurons receive inputs from both cholinergic and GABAergic MS neurons, whereas inhibitory neurons receive a great majority of inputs from GABAergic MS neurons. Both cell types also receive weaker input from glutamatergic MS neurons. Comparisons of inputs to CA1 PV+ interneurons versus SOM+ interneurons showed similar strengths of input from the subiculum, but PV+ interneurons received much stronger input than SOM+ neurons from CA3, the EC, and the MS. Thus, rabies tracing identifies hippocampal circuit connections and maps how the different input sources to CA1 are distributed with different strengths on each of its constituent cell types.

    View details for DOI 10.1016/j.celrep.2014.02.030

    View details for Web of Science ID 000334298200026

    View details for PubMedID 24656815

    View details for PubMedCentralID PMC3998524

  • Cell-type specific inactivation of hippocampal CA1 disrupts location-dependent object recognition in the mouse LEARNING & MEMORY Haettig, J., Sun, Y., Wood, M. A., Xu, X. 2013; 20 (3): 139–46


    The allatostatin receptor (AlstR)/ligand inactivation system enables potent regulation of neuronal circuit activity. To examine how different cell types participate in memory formation, we have used this system through Cre-directed, cell-type specific expression in mouse hippocampal CA1 in vivo and examined functional effects of inactivation of excitatory vs. inhibitory neurons on memory formation. We chose to use a hippocampus-dependent behavioral task involving location-dependent object recognition (LOR). The double transgenic mice, with the AlstRs selectively expressed in excitatory pyramidal neurons or inhibitory interneurons, were cannulated, targeting dorsal hippocampus to allow the infusion of the receptor ligand (the allatostatin [AL] peptide) in a time dependent manner. Compared to control animals, AL-infused animals showed no long-term memory for object location. While inactivation of excitatory or inhibitory neurons produced opposite effects on hippocampal circuit activity in vitro, the effects in vivo were similar. Both types of inactivation experiments resulted in mice exhibiting no long-term memory for object location. Together, these results demonstrate that the Cre-directed, AlstR-based system is a powerful tool for cell-type specific manipulations in a behaving animal and suggest that activity of either excitatory neurons or inhibitory interneurons is essential for proper long-term object location memory formation.

    View details for DOI 10.1101/lm.027847.112

    View details for Web of Science ID 000316324400004

    View details for PubMedID 23418393

    View details for PubMedCentralID PMC3578275

  • MicroRNA-19b downregulates insulin 1 through targeting transcription factor NeuroD1. FEBS letters Zhang, Z. W., Zhang, L. Q., Ding, L., Wang, F., Sun, Y. J., An, Y., Zhao, Y., Li, Y. H., Teng, C. B. 2011; 585 (16): 2592-8


    MiR-17-92 cluster miRNAs are disclosed to contribute to the development of multiple organs and tumorigenesis, but their roles in pancreas development remains unclear. In this study, we found that miR-19b, a member of miR-17-92, was highly expressed in the pancreatic progenitor cells, and miR-19b could target the 3' UTR of NeuroD1 mRNA to decrease its protein and mRNA levels. Functional analysis showed that miR-19b exerted little effect on the proliferation of pancreatic progenitors, whereas it inhibited the expression of insulin 1, but not insulin 2 in MIN6 cells. These results suggest that miR-19b can downregulate insulin 1 expression through targeting transcription factor NeuroD1, and thus regulate the differentiation and function of β-cells.

    View details for DOI 10.1016/j.febslet.2011.06.039

    View details for PubMedID 21781967