Molecular mechanisms of STDP define the properties of associative learning in a model of the hippocampal CA1 microcircuit
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1
Vytautas Magnus University, Lithuania
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2
University of Stirling, Institute of Computer Science and Mathematics, United Kingdom
Induction and maintenance of synaptic modifications in spike-timing-dependent plasticity (STDP) involve complex biochemical pathways (Malenka and Bear, 2004). Detailed signal transduction models (see Graupner and Brunel, 2010; Manninen et al, 2010 for review) contribute to the understanding of the mechanisms underlying STDP and allow making grounded predictions about learning properties.
In this study we investigate the influence of CaMKII bistable behaviour on learning at the Schaffer collateral – CA1 neuron synapse in hippocampal CA1 microcircuit during associative learning. Synaptic plasticity varies across the theta cycle, from strong LTP to LTD, putatively corresponding to the storage and recall cycles for information patterns encoded in pyramidal cell activity (Hasselmo et al, 2002). The mechanisms underpinning the phasic changes in plasticity are not clear, but it is likely that inhibition plays a role by affecting levels of electrical activity and calcium levels at synapses. We test the hypothesis that molecular network switches to LTP when inhibition is restricted to the perisomatic region, and to LTD, when inhibition is strong in the dendrites.
We extend a computational model of a biochemical molecular network underlying STDP (Graupner and Brunel, 2007) by including an additional chain of phosphatase PP2A that accounts for LTD (Pi and Lisman, 2008) and verify it applying the pre-post and post-pre STDP stimulation protocols. We use a detailed multicompartmental model of a CA1 pyramidal cell (Poirazi et al, 2003) which is driven by spatially-focussed patterns of excitation and inhibition and embed it in a model of the CA1 microcircuit (Cutsuridis et al, 2010) that also includes basket, axoaxonic, bistratified and OLM cells and inputs from the entorhinal cortex (EC), the CA3 Schaffer collaterals. A trigger of synaptic modifications, the intracellular calcium concentration, is modelled in a spine on a Stratum Radiatum (SR) dendrite of the CA1 pyramidal cell. We use the resulting calcium signals in an extended model of STDP and analyze the activity of CaMKII and phosphatases PP2A and PP2B during theta cycles in the presence and absence of dendritic inhibition.
We show that in the storage cycle, biochemical network is driven to LTP as the EC input-induced dendritic spikes propagate from the Stratum Lacunosum Moleculare (SLM) dendrites to the SR dendritic regions in the CA1 pyramidal cell, coincide with the CA3 inputs and induce large calcium influx into the spine on the SR dendrite. In the recall cycle, the network supports LTD, as dendritic inhibition provided by bistratified cells prevents dendritic spike propagation into the SR region and restricts calcium increase. However, the observed behaviour is valid for short CA1 input presentation as stable LTP is obtained for longer synaptic stimulation. Removing dendritic inhibition in recall cycles allows dendritic spikes reaching SR dendrites and results in LTP.
The results show the effect of the overall time course of stimulus presentation on the final LTD/LTP outcome as well as suggest that dendritic inhibition along with the bistable CaMKII network might act as a filter of short CA3 inputs and prevent learning of unwanted patterns during the recall cycles of the theta rhythm in CA1 pyramidal cell.
Acknowledgements: This research was funded by a grant (No. MIP-93/2010) from the Research Council of Lithuania.
References
1. Cutsuridis V., Cobb S, Graham B.P. (2010). Encoding and retrieval in a model of the hippocampal CA1 microcircuit. Hippocampus, 20:423-446.
2. Graupner M., Brunel N. (2007). STDP in a Bistable Synapse Model Based on CaMKII and Associated Signaling Pathways. PloS Computational Biology, vol. 3, 2299-2323.
3. Graupner M., Brunel N. (2010). Mechanisms of induction and maintenance of spike-timing dependent plasticity in biophysical synapse models . Front. Comput. Neurosci. 4 : 136.
4. Hasselmo M., Bodelon C., Wyble B .(2002). A proposed function of the hippocampal theta rhythm: Separate phases of encoding and retrieval of prior learning. Neural Comput, 14:793–817.
5. Malenka R. C., Bear M. F. (2004). LTP and LTD: an embarrassment of riches . Neuron 44 , 5–21.
6. Manninen T., Hituri K., Kotaleski J.H., Blackwell K.T., Linne M.L. (2010). Postsynaptic signal transduction models for long-term potentiation and depression. Front. Comput. Neurosci . 4:152.
7. Pi H.J., Lisman J.E. (2008). Coupled Phosphatase and Kinase Switches Produce the Tristability Required for Long-Term Potentiation and Long-Term Depression. J. Neurosci. 28(49):13132-13138.
8. Poirazi, P., Brannon, T., Mel, B.W. (2003). Arithmetic of subthreshold synaptic summation in a model CA1 pyramidal cell. Neuron 2003, 37:977-987.
Keywords:
computational neuroscience,
General neuroinformatics
Conference:
4th INCF Congress of Neuroinformatics, Boston, United States, 4 Sep - 6 Sep, 2011.
Presentation Type:
Poster Presentation
Topic:
General neuroinformatics
Citation:
Saudargiene
A,
Slivko
G and
Graham
B
(2011). Molecular mechanisms of STDP define the properties of associative learning in a model of the hippocampal CA1 microcircuit.
Front. Neuroinform.
Conference Abstract:
4th INCF Congress of Neuroinformatics.
doi: 10.3389/conf.fninf.2011.08.00024
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Received:
17 Oct 2011;
Published Online:
19 Oct 2011.
*
Correspondence:
Dr. Ausra Saudargiene, Vytautas Magnus University, Kaunas, Lithuania, ausra.saudargiene@lsmuni.lt