段树民博士简介

Active role of astrocytes in long-term synaptic plasticity.

Although glial cells have been reported to play important roles in various neuronal functions including neurogenesis, synaptogenesis, and modulating synaptic transmission, it is not clear whether and how glial cells contribute to long-term potentiation (LTP), - a form of synaptic plasticity believed to be a cellular basis for learning and memory. To directly address this issue, we have established two types of hippocampal cultures - neurons cultured on a layer of astrocytes (mixed cultures) or in glia conditioned medium (GCM) without direct contact with astrocytes (GCM cultures). We found that LTP could be evoked in mixed cultures but not in GCM cultures. Further results from both hippocampal slices and cultured neurons indicate that, by providing extracellular D-serine that facilitates activation of NMDA receptors, astrocytes directly supports the induction of LTP. We have also directly recorded astrocyte currents in hippocampal slice in response to stimulation of Schaffer collaterals. Interestingly, induction of LTP in CA1 neurons also induced long-term increase in astrocyte currents in response to Schaffer collateral stimulation(See Fig.1). We are currently examining the underlying mechanisms and its functional significance of the latter form of neuron-glia interaction.

Activity- dependent heterosynaptic modulation mediated by astrocyte released factors.

High levels of neuronal activity have been reported to cause spillover of neurotransmitter to neighboring synapses and induce heterosynaptic modulation via presynaptic receptors, suggesting that neuronal information processing involves not only homosynaptic transmission via activated synaptic connections but also heterosynaptic interactions between adjacent synaptic inputs. Using dual whole-cell recordings from pairs of interconnected hippocampal neurons in mixed cultures and GCM cultures, we found that glutamatergic synaptic activity activates non-NMDA receptors of nearby astrocytes and induces ATP release from these cells, which in turn causes heterosynaptic suppression. Thus, besides the spillover of neurotransmitters from synapses, signaling molecule released from astrocytes, e.g., ATP, can also mediate neuronal activity-dependent heterosynaptic modulation. Such neuron-glia crosstalks may play a role in activity-dependent signal processing and plasticity of neural networks. We are further examining if such neuron-glia crosstalk also exists in more intact tissues, using brain slice preparations(See Fig.1).

Activity-dependent synaptogenesis.

The development of synaptic connections -the formation, elimination, stabilization and maturation of synapses - is shaped by neuronal activity, a process critical for experience-dependent refinement of neuronal circuits. Using a combination of experimental approaches, including electrophysiology, immunochemistry(See Fig.2), GFP-linked gene transfection(See Fig.3), two-photon fluorescence microscopy (See Fig.4), and calcium imaging(See Fig.5), we are studying the trafficking of pre- and postsynaptic molecules induced by neuronal activities in cultured neurons and brain slices. In particular, we are interested in determining whether astrocytes are involved in this neuronal activity-dependent synapse development. We are also interested in studying how 'new' neurons derived from neural stem cells become incorporated into (form synapses with) existing neuronal circuits.

Guidance of Glial Cell Migration.

Growth and migration of glial processes are important not only in neuronal development, e.g., guiding neuronal migration , but also in neuronal degeneration and regeneration, but the underlying mechanisms are largely unknown. We are interested in studying whether glia cell migration and process extension share the same molecules and signal transduction mechanisms with that of neuronal migration and axon guidance, and how guidance of migration and growth of these neurons and glial cells are regulated through their reciprocal interactions.

Publications

Li, C., Lu, J., Wu, J., Duan, S., and Poo, M. (2004) Bidirectional Modification of Presynaptic Neuronal Excitability Accompanying Spike Timing-Dependent Synaptic Plasticity. Neuron 41, 257-268.

Yang, Y., Ge, W., Chen, Y., Zhang, Z., Shen, W., Wu, C., Poo, M., and Duan, S. (2003) Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine. PNAS, 100: 15194-15199.

Zhang, J., Wang, H., Ye, C., Ge, W., Chen, Y., Jiang, Z., Wu, C., Poo, M. and Duan, S. (2003) ATP Released by Astrocytes Mediates Glutamatergic Activity-Dependent Heterosynaptic Suppression. Neuron, 40: 971-982.

Duan, S., Anderson C. M. , Keung, E. C., Chen, Y., Chen, Y., and Swanson R. A.(2003) P2X7 Receptor-Mediated Release of Excitatory Amino Acids from Astrocytes. J Neurosci, 23: 1320-1328

Wang, Z., Xu, N., Wu,CP., Duan, S., and Poo, M. (2003) Bidirectional changes in spatial dendritic integration accompanying long-term synaptic modifications. Neuron, 37: 463-472

Yuan, X., Jin, M., Xu, X., Wu, CP., Poo, M., and Duan, S.(2003) Signalling and crosstalk of Rho GTPases in mediating axon guidance. Nature Cell Biol , 5, 38 - 45 [Abstract]

Note: This paper is cited by Nature Signaling Gateway as a Featured Article.