Tao Jin

All Publications

• Cocaine Hijacks the <i>Npas4</i>-dependent Somatostatin Ensembles in the mPFC to Mediate Attention NEUROSCIENCE BULLETIN Hou, X., Han, K., Wang, F., Jiang, C., Ma, L., Jin, T. 2026

  Abstract

  Cocaine disrupts the physiological function of the prefrontal cortex and impairs attention, short-term memory, and other cognitive functions. However, the specific cellular basis of maladaptation remains poorly understood. Here, using neuronal activity-dependent tagging, rabies retrograde tracing, electrophysiological recording, and behavioral analyses in mice, we show that a single injection of cocaine increases the recruitment of both the Npas4 transcription-dependent ensemble (N-RAM) and the N-RAM+ somatostatin-expressing interneuron (N-RAM+ SST-IN) ensemble in the medial prefrontal cortex (mPFC). Npas4 induction in mPFC SST-INs upregulates plasticity and excitatory synaptic input from the mediodorsal thalamus (MD). Chemogenetic inhibition of either the N-RAM+ or N-RAM+ SST-IN ensemble in the mPFC impaired attention in the 5‑choice serial reaction time task (5-CSRTT). Our study identifies a unique role of the mPFC N-RAM+ SST-IN ensemble in regulating attention following acute cocaine injection, providing a potential therapeutic target for attention deficits.

  View details for DOI 10.1007/s12264-026-01689-0

  View details for Web of Science ID 001829819100001

  View details for PubMedID 42501223

  View details for PubMedCentralID 3867253

• The intrinsic excitability of and autophagy protein expression levels in dentate gyrus ensembles regulate fear generalization. Neural regeneration research Lin, Q., Jin, T., Yang, Y., Hou, X., Chen, R., Ma, L., Liu, X., Wang, F. 2026; 21 (7): 3073-3082

  Abstract

  The overgeneralization of fear is associated with psychiatric disorders and cognitive decline. Recent studies have shown that engram cells in the dorsal dentate gyrus are integrated into functionally heterogeneous ensembles that are involved in contextual fear memory generalization and discrimination. However, the intracellular signals that promote fear generalization remain to be fully elucidated. In this study, we labeled and manipulated the c-Fos+ and Npas4+ ensembles in the dorsal dentate gyrus that are activated by contextual fear conditioning using a robust activity marking system. The results showed that increasing the excitability of Fos-dependent robust activity marking by overexpressing NaChBac or decreasing the excitability of Npas4-dependent robust activity marking by overexpressing Kir2.1 promoted fear memory generalization. Furthermore, CRISPR-mediated downregulation of the autophagy-related Atg5 or Atg7 genes in dorsal dentate gyrus neurons inhibited activation of c-Fos, but not Npas4. Knockdown of Atg5 or Atg7 in the Fos-dependent robust activity marking or Npas4-dependent robust activity marking ensemble led to an increase in neuronal excitability and a decrease in spine density in both ensembles. However, Atg7 knockdown in the Fos-dependent robust activity marking ensemble promoted memory generalization, while knockdown of Atg5 or Atg7 in the Npas4-dependent robust activity marking ensemble increased anxiety levels. These results contribute to our understanding of how the varying plasticity of memory engrams is involved in regulating fear memory generalization and anxiety.

  View details for DOI 10.4103/NRR.NRR-D-24-01026

  View details for PubMedID 40536998

  View details for PubMedCentralID PMC13378950

• Distinct roles of NPTX1 and NPTX2 in synaptic transmission of the fear memory engrams in the dentate gyrus. Neuroreport Mao, F., Yang, Y., Jiang, Z., Le, Q., Jin, T. 2026; 37 (9): 351-358

  Abstract

  The synaptic transmission of memory engrams is important for their roles in memory storage and retrieval, and can be regulated by multiple neuronal adhesion molecules. This study focuses on the roles of neuronal pentraxin (NPTX) family members (NPTX1 and NPTX2), which are biomarkers for cognitive decline, in the synaptic transmission of Fos-(F-RAM) and Npas4-(N-RAM)-dependent engrams formed during contextual fear conditioning in the dentate gyrus.Utilizing robust activity marking (RAM) system, contextual fear conditioning, conditional knockout (cKO) technology and electrophysiological recording, we analyzed the characteristic of miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) in engram cells of wild-type and Nptxs cKO mice.Nptx1 cKO leads to an increased amplitude and frequency of mEPSCs and decreased amplitude of mIPSCs in F-RAM neurons, as well as an elevated mEPSC frequency and reduced mIPSC frequency in N-RAM neurons. In contrast, Nptx2 cKO results in a decreased mEPSC frequency and increased mIPSC frequency in both F-RAM and N-RAM neurons.Nptx1 cKO increased engram activity while Nptx2 cKO decreased engram activity. These findings reveal the distinct roles of the NPTX family in regulating the synaptic transmission of the fear engrams.

  View details for DOI 10.1097/WNR.0000000000002272

  View details for PubMedID 42132754

• Disturbed engram network caused by NPTX downregulation underlies aging-related contextual fear memory deficits. Cell research Jin, T., Yang, Y., Guo, Y., Zhang, Y., Le, Q., Huang, N., Liu, X., Yu, J., Ma, L., Wang, F. 2025; 35 (9): 656-674

  Abstract

  Engram cells storing episodic memories are allocated to separate neuronal ensembles. However, how these ensembles maintain their stability to drive precise memory expression, and whether their destabilization contributes to aging-related memory deficits, remain elusive. Here, we show that during contextual fear memory consolidation, neuronal pentraxin 1 (NPTX1) in Fos transcription-dependent ensemble (F-RAM) of the dentate gyrus (DG) promotes memory expression in the fear context. NPTX1 facilitates Kv7.2 channel-mediated inhibition of engram cell hyperexcitability, thereby restricting the response of these cells to excitatory inputs from medial entorhinal cortex. Meanwhile, NPTX2 enhances the perisomatic inhibition of Npas4 transcription-dependent ensemble (N-RAM) by parvalbumin+ (PV+) interneurons, thereby preventing fear memory overgeneralization. Pharmacological activation of Kv7.2 channels or chemogenetic activation of PV+ interneurons repaired memory deficits caused by engram-specific NPTX depletion. Contextual fear memory precision and NPTX expression in DG engram cells were decreased in aged mice. Overexpressing NPTX1 in F-RAM ensemble or the AMPAR-binding domain of NPTX2 in N-RAM ensemble rescued contextual fear memory deficits. These findings elucidate that the coordination of NPTX1 and NPTX2 prevents engram ensembles from becoming hyperactive and provide a causal link between engram network destabilization and aging-related contextual fear memory deficits.

  View details for DOI 10.1038/s41422-025-01157-w

  View details for PubMedID 40750687

  View details for PubMedCentralID PMC12408839

• Dorsal hippocampus- and ACC-projecting medial septum neurons differentially contribute to the recollection of episodic-like memory. FASEB journal : official publication of the Federation of American Societies for Experimental Biology Jin, T., Chen, R., Shao, M., Yang, X., Ma, L., Wang, F. 2020; 34 (9): 11741-11753

  Abstract

  Episodic memory refers to the recollection of previous experiences containing specific temporal, spatial, and emotional information. The ability to recollect episodic memory requires coordination of multiple brain regions, including the hippocampus (HPC) and the cingulate cortex. While the afferents into HPC and cingulate cortex that orchestrate the episodic memory remain unclear. The medial septum (MS), one of the anatomical location of cholinergic centers, innervates not only the dorsal HPC (dHPC), but also the cingulate and entorhinal cortices. By using "What-Where-When" episodic-like memory (ELM) behavioral model and viral tracing, we found that MS neurons projected to dHPC and anterior cingulate cortex (ACC), which exerted distinct impacts on ELM recollection. Chemogenetic inhibition of the dHPC-projecting MS neurons disrupted "What-Where-When" ELM recollection as well as object location, object-in-place, and recency recognition memories recollection, while chemogenetic inhibition of the ACC-projecting MS neurons only disrupted "What-Where-When" ELM recollection. Moreover, neither dHPC- nor ACC-projecting MS neurons were involved in novel object recognition memory recollection or locomotor activity. Immunostaining showed that ACC- and dHPC-projecting MS neurons are partially overlapped populations. These findings reveal an unsuspected division of ELM processing and provide the potential mechanism that the recollection of episodic memory need the coordination of MS neurons projecting to dHPC and ACC.

  View details for DOI 10.1096/fj.202000398R

  View details for PubMedID 32652689

• Retrieval-Driven Hippocampal NPTX2 Plasticity Facilitates the Extinction of Cocaine-Associated Context Memory. Biological psychiatry Wang, Z., Jin, T., Le, Q., Liu, C., Wang, X., Wang, F., Ma, L. 2020; 87 (11): 979-991

  Abstract

  Postretrieval extinction attenuates the pathological memory associated with psychiatric states such as drug addiction in both humans and rodents. The extinction of a learned response requires gene transcription and protein synthesis after memory retrieval in a time-dependent manner, yet the precise physiological basis after retrieval to allow extinction to neutralize a learned behavior is not fully understood.In a cocaine conditioned place preference paradigm, we used a ribosomal tagging strategy to measure the translational state of hippocampal pyramidal neurons after the retrieval of cocaine-associated context memory. Using approaches of electrophysiology, neuronal tracing, and a doxycycline-dependent robust activity marking system, we investigated the cellular and molecular basis of retrieval-induced plasticity that facilitated the extinction.Bioinformatics analysis discovered the specific translational regulation of signaling pathways by retrieval and revealed Nptx2 as the hub gene. Manipulating Nptx2 in dorsal hippocampus bidirectionally regulated the extinction of cocaine-associated context memory as well as the retrieval-driven synaptic remodeling. The pentraxin (PTX) domain of NPTX2 recruited GluA1-AMPA receptors and enhanced the extinction and excitatory synaptic transmission that was prevented by overexpressing carboxyl cytoplasmic tail of GluA1. Furthermore, Nptx2 in retrieval-activated neurons was required for the extinction.The retrieval-driven upregulation of Nptx2 contributes to the synaptic remodeling in dorsal hippocampus and facilitates the extinction of cocaine-associated context memory, indicating a potential target for the treatment of cue-induced cocaine seeking.

  View details for DOI 10.1016/j.biopsych.2019.10.009

  View details for PubMedID 31836174

• An in Vitro Assay of hERG K + Channel Potency for a New EGFR Inhibitor FHND004. Frontiers in pharmacology Jin, T., Hu, B., Chen, S., Wang, Q., Dong, X., Zhang, Y., Zhu, Y., Zhang, Z. 2018; 9: 577

  Abstract

  FHND004 is a newly synthesized epidermal growth factor receptor (EGFR) inhibitor for the treatment of non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the impacts of FHND004 on human ether-à-go-go-related gene (hERG) K+ channels and the molecular mechanisms underlying of its action. Whole-cell patch clamp recording was performed on wild type (WT), mutant hERG channels heterologously expressed in human embryonic kidney (HEK) 293 cells or IKr endogenously expressed in HL-1 cells, respectively. FHND004 inhibited hERG K+ currents in a concentration-dependent manner with IC50 values of 8.46 ± 0.33 μM in HEK293 cells and 7.52 ± 1.27 μM in HL-1 cells, respectively. However, the inhibitory potency of FHND004 on hERG channels was significantly less than its precursor AZD9291. FHND004-induced inhibition was state-dependent with a preference within open state, but did not alter other kinetics including activation, inactivation, and recovery from inactivation or deactivation. In addition, FHND004 exhibited more potent inhibitory effects on WT/A422T and WT/H562P-hERG, two known long QT syndrome (LQTS) associated KCNH2 mutations, than WT alone. Mutations of the residues at pore regions (F656C, Y652A, S624A, and F557L) in hERG channels attenuated block effects of FHND004. Taken together, our results demonstrate the evidence that FHND004 is a less potent hERG blocker than its precursor AZD9291. There is, however, a need for caution in the potential use of FHND004 for treating NSCLC patients, especially in those with other concurrent triggering factors.

  View details for DOI 10.3389/fphar.2018.00577

  View details for PubMedID 29904349

  View details for PubMedCentralID PMC5990611

• Design, synthesis, SAR discussion, in vitro and in vivo evaluation of novel selective EGFR modulator to inhibit L858R/T790M double mutants. European journal of medicinal chemistry Zhang, H., Wu, W., Feng, C., Liu, Z., Bai, E., Wang, X., Lei, M., Cheng, H., Feng, H., Shi, J., Wang, J., Zhang, Z., Jin, T., Chen, S., Hu, S., Zhu, Y. 2017; 135: 12-23

  Abstract

  Based upon the modeling binding mode of marketed AZD9291 with T790M, a series of 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline derivatives were designed and synthesized with the purpose to overcome the drug resistance resulted from T790M/L858R double mutations. The most potent compound 8 showed excellent enzyme inhibitory activities and selectivity with sub nanomolar IC50 values for both the single L858R and double T790M/L858R mutant EGFRs, and was more than 8-fold selective for wild type EGFR. Compound 8 exhibited good microsomes stabilities and pharmacokinetic properties and lower binding affinity to hERG ion channel than AZD9291 and displayed strong antiproliferative activity against the H1975 non-small cell lung cancer (NSCLC) cells bearing T790M/L858R and in vivo anticancer efficacy in a human NSCLC (H1975) xenograft mouse model.

  View details for DOI 10.1016/j.ejmech.2017.04.036

  View details for PubMedID 28426996

• Physical and functional interaction of Snapin with Cav1.3 calcium channel impacts channel protein trafficking in atrial myocytes. Cellular signalling Sun, X. L., Yuan, J. F., Jin, T., Cheng, X. Q., Wang, Q., Guo, J., Zhang, W., Zhang, Y., Lu, L., Zhang, Z. 2017; 30: 118-129

  Abstract

  The L-type Ca2+ channel (LTCC) Cav1.3 plays a critical role in generating electrical activity in atrial myocytes and cardiac pacemaker cells. However, the molecular and functional basis of Cav1.3 modulation in atrial myocytes has not yet been fully understood. By using the yeast two-hybrid system (Y2H), a Cav1.3-associated protein was screened, which was identified as Snapin. Physical interaction and co-localization between Snapin and Cav1.3 were then confirmed in both the heterologous expression system and mouse atrial myocytes. Direct interaction between them was additionally addressed in a GST pull down assay. Furthermore, both total and membrane expressions of Cav1.3 were significantly impaired by Snapin overexpression, resulting in the ubiquitin-proteasomal degradation of Cav1.3 and a consequent reduction of the densities of whole-cell ICa-L. Snapin-induced down-regulation of Cav1.3 was reversed by SNAP-23 competitively. What is more important is that the depressed-expression of Cav1.3 paralleled with enhanced-expression of Snapin was documented in atrial samples from atrial fibrillation (AF) patients. Our results provide the evidence of a direct regulatory role of Snapin on Cav1.3 channels in atrial myocytes, and highlight a potential role of Snapin in the regulation of Cav1.3 in atrial arrhythmogenesis.

  View details for DOI 10.1016/j.cellsig.2016.11.019

  View details for PubMedID 27915047

• Profiling metabolic remodeling in PP2Acα deficiency and chronic pressure overload mouse hearts. FEBS letters Dong, D., Li, L., Gu, P., Jin, T., Wen, M., Yuan, C., Gao, X., Liu, C., Zhang, Z. 2015; 589 (23): 3631-9

  Abstract

  Our understanding of how metabolic switches occur in the failing heart is still limited. Here, we report the emblematic pattern of metabolic alternations in two different mouse models. PP2Acα deficient hearts exhibited a dramatic decrease in the levels of mRNA encoding for transporters and enzymes involved in glucose utilization, which compensated by higher expression levels of genes controlling fatty acid utilization. These features were partly reproduced in cultured PP2Acα KD cardiomyocytes. Equivalently, a decrease in the expression of most of the transporters and enzymes controlling both glucose and fatty acid metabolism were observed in TAC model.

  View details for DOI 10.1016/j.febslet.2015.10.016

  View details for PubMedID 26497085