Sari Lauri, PhD Docent in Neurobiology, Project leader Neuroscience Center and Department of Bio- and Environmental Sciences/ Physiology P.O.Box 65, FIN- 00014 University of Helsinki, Finland Phone +358-9-19159865 Fax +358-9-19159810 Email sari.-dot-lauri-at- helsinki-dot-fi

Signaling Mechanisms Guiding Functional Maturation of Glutamatergic Synapses

Formation of neuronal circuits is a highly dynamic process of rapid and concurrent formation and elimination of synaptic connections. During this early development, immature neuronal networks typically display spontaneous, rhythmic activity, which is thought to be instrumental for the development of the synaptic circuitry.

Exactly how activity shapes synaptic connectivity during development and the molecular mechanisms underlying these processes are still largely unknown. The key question is what are the cellular and molecular mechanisms that link electrical activity to changes in synaptic structure and how are these regulated during development. To understand this process, we focus on studying the glutamate receptor mechanisms to detect specific patterns of endogenous activity in the immature hippocampus as well as in the downstream signaling cascades converting receptor activity into long-lasting synaptic imprints. 
Our experimental approach involves the use of in vitro electrophysiological techniques in combination with pharmacological and local genetic manipulation of neuronal activity in various neonatal hippocampal preparations.

Our current main research interests are
1) the physiological functions and developmental regulation of kainate–type ionotropic glutamate receptors in the immature hippocampus; and  
2) activity-dependent mechanisms guiding presynaptic maturation at developing glutamatergic synapses. We aim to understand how the fast Hebbian and the slow, homeostatic plasticity mechanisms operate in the developing circuitry and how they might control the transition from the immature to the mature presynaptic function.

Personnel in the laboratory of synaptic development and plasticity
Project leader: Docent, Academy Research Fellow Sari Lauri, PhD
Group leader: Docent Tomi Taira, PhD
Post-doctoral fellow: Sabine Koch, PhD
Graduate students: Johanna Huupponen, MSc; Juuso Juuri, MSc; Marko Sallert, MSc; Aino Vesikansa, MSc
Undergraduate student: Suvi Pousi

Selected publications
Sallert M, Rantamaki T, Vesikansa A, Anthoni H, Harju K, Yli-Kauhaluoma J, Taira T, Castren E  and Lauri SE (2009). Brain-Derived Neurotrophic Factor Controls Activity-Dependent Maturation ofCA1Synapses by Downregulating Tonic Activation of Presynaptic Kainate Receptors. J. Neurosci. 29(36):11294 –11303

Hanse E, Taira T, Lauri S and Groc L (2009). Glutamate synapse in developing brain: an
integrative perspective beyond the silent state. Trends Neurosci , 10.1016/j.tins.2009.07.003

Huupponen, J., Molchanova, S., Taira, T., and Lauri, S.E. (2007). Susceptibility for homeostatic plasticity is downregulated in parallel with maturation of the hippocampal synaptic circuitry. J. Physiol. 581(Pt 2): 505-514.   

Vesikansa, A., Sallert, M., Taira, T., and Lauri, S.E. (2007). Activation of kainate receptors controls density of functional glutamatergic synapses in the area CA1 of hippocampus. J. Physiol. 583(Pt 1): 145-157.

Sallert, M., Malkki, H., Segerstråle, M., Taira, T., and Lauri, S.E. (2007). Effects of the kainate receptor agonist ATPA on glutamatergic synaptic transmission and plasticity during early postnatal development. Neuropharmacology 52(6): 1354-1365.

Lauri, S.E., Vesikansa, A., Segerstråle, M., Collingridge, G.L., Isaac, J.T.R., and Taira, T. (2006). Functional maturation of CA1 synapses involves activity-dependent loss of tonic kainate receptor-mediated inhibition of glutamate release. Neuron 50(3): 415-429.

Lauri, S.E., Segerstråle, M., Vesikansa, A., Maingret, F., Mulle, C., Collingridge, G.L., Isaac, J.T.R., and Taira, T. (2005). Endogenous activation of kainate receptors regulates glutamate release and network activity in the developing hippocampus. J. Neuroscience 25(18): 4473.

Lauri, S.E., Bortolotto, Z.A., Bleakman, D., Ornstein, P.L., Lodge, D., Isaac, J.T.R., and Collingridge, G.L. (2003). A role for Ca2+ stores in kainate-dependent synaptic facilitation and LTP at mossy fibre synapses in the hippocampus. Neuron 39: 327-341.  

Lauri, S.E., Bortolotto, Z.A, Bleakman, D., Ornstein, P.L., Lodge, D., Isaac, J.T.R., and Collingridge, G.L. (2001). A critical role of a facilitatory kainate autoreceptor in mossy fibre LTP. Neuron 32: 697-709.