Cellular and molecular aspects of neural signaling：
Our brains accomplish (or sometimes fail at) their jobs by generating coordinated patterns of electrical signals in groups of nerve cells. Research in my laboratory focuses on the general question of how this coordination occurs. Circuits, single synaptic connection and electrical properties particular to individual nerve cells combine to allow neurons to generate the specific firing patterns that ultimately result in thoughts, feelings and behaviors. My work concentrates on the cerebellar cortex, a region of the brain involved in coordinating movements. While a great deal is known about the firing patterns of particular types of cells in this part of the brain, we have a rudimentary understanding of how its circuitry generates these signals and modifies them during learning and memory. Different to some brain regions, like the hippocampus, which receive complex information, the cerebellum is made up of 6 types of neurons whose connectivity and ultrastructure are known in detail, but offers a remarkable context for neuronal activities including learning and memory issues. Surprisingly, most of this connectivity can be preserved in a 0.4 mm thick slice preparation of the cerebellum. In the reduced preparation, the output can be easily monitored, and each input can be reliably stimulated.
One set of projects in the lab explores a curious feature of the main output neurons of the cerebellum, the Purkinje cells (PCs). Over the last 20 years, plasticities in this cell have been implicated, like LTD and LTP of the parallel fiber-Purkinje cell synapse, which are critical for some forms of motor learning, like eye-blink conditioning. We discovered a new form of plasticity, LTD at the climbing fiber-Purkinje cell synapse, which is expressed at post-synaptic level. Currently, we are studying intracellular and intercellular signal moleculars, which may affect this LTD. For example, is there cross-talk between parallel fiber and climbing fiber? Is there possible function of neurotrophin on this plasticity? Our current projects are aiming at answering these questions.
A second set of projects examines neurotransmitter at excitatory synaptic connections. Neurotransmitters transmit neuronal signals in chemical synapses and transmitter transporters take back transmitters up into cells. This is interesting to us because this mechanism is the target of action of very important classes of drugs including selective serotonin reuptake inhibitors (e.g. Prozac), amphetamines, and cocaine. Recently, we provided first recording that neuronal glutamate transporter can itself undergo long-term potentiation (LTP), which supplied a new clue for understanding action of neurotransmitters in neuronal activities. However, unanswered questions are still remained: How does neurotransmitter uptake influence the strength of synaptic signals? Does uptake help to determine which targets in the synapse? Is the process of transmitter uptake change involved in neurologic disorders? These and related questions are being addressed with a multidisciplinary approach combining electrophysiology, optical imaging of single neurons, and virus-mediated delivery of fluorescently-labeled signaling proteins.
Finally, we are also studying some molecular signal proteins and genes involved in neuronal activities. These studies are based on broad collaboration domestically and in abroad. For instance, we first report that SRF (serum response factor) is critical to hippocampal LTP, but not CREB (cyclic AMP response element binding protein) that was well-known. We are now studying detailed action patterns of SRF. Other signal moleculars also include neurotrophine, developmental factors and new gene.
發(fā)表論文：
1.Steinberg JP*, Takamiya K*, Shen Y, Xia J, Rubio ME, Yu S, Jin W, Thomas GM, Linden DJ and Huganir RL（2006)Deficient cerebellar long-term depression in mice lacking PICK1, the GluR2 C-terminal PDZ ligand, and GluR2 PKC-Mediated Phosphorylation. Neuron, in press. (* co-first authors) (SCI影響因子: 14.4)
2.Shen Y and Linden DJ (2005) Long-term potentiation of neuronal glutamate transporter. Neuron 46, 715. (SCI影響因子: 14.4)
3.Ramanan N, Shen Y, Sarsfield SL, Linden DJ and Ginty DD (2005) Distinct requirements for SRF and CREB in neuronal survival and synaptic plasticity. Nature Neuroscience 8, 759. (SCI影響因子: 17.0)
4.Shen Y, Hansel C and Linden DJ (2002) Glutamate release monitored during LTD at the cerebellar Climbing Fiber-Purkinje neuron synapse. Nature Neuroscience 5, 725. (SCI影響因子: 17.0)
5.Yang XL, Li P, Lu T, Shen Y and Han MH (2001) Physiological and pharmacological characterization of glutamate and GABA receptors on carp retinal neurons. Progress in Brain Research 131, 277. (SCI影響因子: 2.9)
6.Shen Y, Zhou Y and Yang XL（1999)Characterization of AMPA receptors on isolated amacrine-like cells in carp retina. European Journal of Neuroscience 11, 4233. (SCI影響因子: 3.8)
7.Shen Y, Lu T and Yang XL （1999)Modulation of desensitization at glutamate receptors in isolated crucian carp horizontal cells by concanavalin A, cyclothiazide, aniracetam and PEPA. Neuroscience 89, 979. (SCI影響因子: 3.5)
8.Shen Y and Yang XL (1999) Zinc modulation of AMPA receptors may be relevant to splice variants in carp retina. Neuroscience Letters 259, 177. (SCI影響因子: 2.0)
9.Lu T, Shen Y and Yang XL (1998) Desensitization of AMPA receptors on horizontal cells isolated from crucian carp retina. Neuroscience Research 31, 123. (SCI影響因子: 2.2)
10.Han MH, Shen Y and Yang XL (2000) Dynamic difference of GABAC and GABAA receptors in carp retinal bipolar cells. 中國科學(xué) 3, 233.
11.楊雄里, 沈穎, 韓明虎 (1999) Glutamte and -aminobutyric acid receptors and their characteristics in retina. 科學(xué)通報 44, 1548，綜述.
