All Publications

  • Retinoic acid-gated BDNF synthesis in neuronal dendrites drives presynaptic homeostatic plasticity. eLife Thapliyal, S., Arendt, K. L., Lau, A. G., Chen, L. 2022; 11


    Homeostatic synaptic plasticity is a non-Hebbian synaptic mechanism that adjusts synaptic strength to maintain network stability while achieving optimal information processing. Among the molecular mediators shown to regulate this form of plasticity, synaptic signaling through retinoic acid (RA) and its receptor, RARalpha, has been shown to be critically involved in the homeostatic adjustment of synaptic transmission in both hippocampus and sensory cortices. In this study, we explore the molecular mechanism through which postsynaptic RA and RARalpha regulates presynaptic neurotransmitter release during prolonged synaptic inactivity at mouse glutamatertic synapses. We show that RARalpha binds to a subset of dendritically sorted brain-derived neurotrophic factor (Bdnf) mRNA splice isoforms and represses their translation. The RA-mediated translational de-repression of postsynaptic BDNF results in the retrograde activation of presynaptic Tropomyosin receptor kinase B (TrkB) receptors, facilitating presynaptic homeostatic compensation through enhanced presynaptic release. Together, our study illustrates a RA-mediated retrograde synaptic signaling pathway through which postsynaptic protein synthesis during synaptic inactivity drives compensatory changes at the presynaptic site.

    View details for DOI 10.7554/eLife.79863

    View details for PubMedID 36515276

  • Homeostatic plasticity and excitation-inhibition balance: The good, the bad, and the ugly. Current opinion in neurobiology Chen, L., Li, X., Tjia, M., Thapliyal, S. 2022; 75: 102553


    In this review, we discuss the significance of the synaptic excitation/inhibition (E/I) balance in the context of homeostatic plasticity, whose primary goal is thought to maintain neuronal firing rates at a set point. We first provide an overview of the processes through which patterned input activity drives synaptic E/I tuning and maturation of circuits during development. Next, we emphasize the importance of the E/I balance at the synaptic level (homeostatic control of message reception) as a means to achieve the goal (homeostatic control of information transmission) at the network level and consider how compromised homeostatic plasticity associated with neurological diseases leads to hyperactivity, network instability, and ultimately improper information processing. Lastly, we highlight several pathological conditions related to sensory deafferentation and describe how, in some cases, homeostatic compensation without appropriate sensory inputs can result in phantom perceptions.

    View details for DOI 10.1016/j.conb.2022.102553

    View details for PubMedID 35594578

  • Differential Regulation of Innate and Learned Behavior by Creb1/Crh-1 in Caenorhabditis elegans JOURNAL OF NEUROSCIENCE Dahiya, Y., Rose, S., Thapliyal, S., Bhardwaj, S., Prasad, M., Babu, K. 2019; 39 (40): 7934–46


    Memory formation is crucial for the survival of animals. Here, we study the effect of different crh-1 [Caenorhabditis elegans homolog of mammalian cAMP response element binding protein 1 (CREB1)] isoforms on the ability of C. elegans to form long-term memory (LTM). Null mutants in creb1/crh-1 are defective in LTM formation across phyla. We show that a specific isoform of CREB1/CRH-1, CRH-1e, is primarily responsible for memory related functions of the transcription factor in C. elegans Silencing of CRH-1e-expressing neurons during training for LTM formation abolishes the LTM of the animal. Further, CRH-1e expression in RIM neurons is sufficient to rescue LTM defects of creb1/crh-1-null mutants. We go on to show that apart from being LTM defective, creb1/crh-1-null animals show defects in innate chemotaxis behavior. We further characterize the amino acids K247 and K266 as responsible for the LTM related functions of CREB1/CRH-1 while being dispensable for its innate chemotaxis behavior. These findings provide insight into the spatial and temporal workings of a crucial transcription factor that can be further exploited to find CREB1 targets involved in the process of memory formation.SIGNIFICANCE STATEMENT This study elucidates the role of a specific isoform of CREB1/CRH-1, CRH-1e, in Caenorhabditis elegans memory formation and chemosensation. Removal of this single isoform of creb1/crh-1 shows defects in long-term memory formation in the animal and expression of CREB1/CRH-1e in a single pair of neurons is sufficient to rescue the memory defects seen in the mutant animals. We further show that two specific amino acids of CRH-1 are required for the process of memory formation in the animal.

    View details for DOI 10.1523/JNEUROSCI.0006-19.2019

    View details for Web of Science ID 000488506700011

    View details for PubMedID 31413073