Computational model of CA1 pyramidal cell with meta-STDP stabilizes under ongoing spontaneous activity as in vivo Matúš Tomko, Ľubica Beňušková Centre for Cognitive Science, DAI FMPI UK, Mlynská dolina, 84248 Bratislava, Slovakia matus.tomko@fmph.uniba.sk; lubica@ii.fmph.uniba.sk Peter Jedlička Institute of Medical Informatics, Faculty of Medicine, Justus-Liebig-University, Rudolf-Buchheim-Str. 6, D-35392 Giessen, Germany peter.jedlicka@informatik.med.uni-giessen.de Abstract Synaptic plasticity is the basic mechanism of learning and memory. It is the ability of neurons to change efficacies of synaptic weights in response to stimuli. There is no general agreement on which synaptic plasticity rule(s) hold in the brain, although some general principles have been agreed upon. Thus, we implemented the Spike- Timing Dependent Plasticity rule with metaplasticity (meta-STDP) in a biophysically realistic computational model of hippocampal CA1 pyramidal cell in order to model synaptic plasticity in alive hippocampus. Characteristic feature of the brain in vivo is an ongoing spontaneous or background activity in neural circuits. Neurons should not change their weights as a result of this background activity, only when a statistically different pattern of input activity appears. As a first step in our research, we subjected our CA1 model to realistically simulated input activity and we have achieved realistic output spontaneous activity and stabilization of synaptic weights after a short time. 1 Introduction Synaptic plasticity is ability of synapses to change their strength or efficacy of the synaptic transmission according to input/output activity (Hughes, 1958). It is considered as a critical neural mechanism for learning and memory. In the field of hippocampus, the research is focused primarily on long-term synaptic changes lasting minutes, hours, or months. They are called long- term potentiation (LTP) and long-term depression (LTD) of synaptic efficacy. Several models of synaptic plasticity have been proposed (Mayr and Partzsch, 2010). Meta-STDP rule (Benuskova and Abraham, 2007) is a synaptic rule that combines classical STDP (spike-timing dependent plasticity; Markram et al., 1997) and metaplasticity (Abraham, 2008). The main idea of metaplasticity is that previous presynaptic and postsynaptic activity affects the sign and size of synaptic plasticity at the stimulated synapses (Abraham, 2008). Benuskova and Abraham (2007) used this approach to modify classical STDP rule. Magnitudes of LTP / LTD in the meta-STDP are dynamically changed as a function of a previous average postsynaptic activity (Benuskova and Abraham, 2007). Computational models of the granule cell endowed with this rule were able to reproduce experimental results of synaptic plasticity occurring in the dentate gyrus, provided the model exhibited ongoing spontaneous activity (Benuskova and Abraham, 2007; Jedlička et al., 2015). Based on computer simulations, the authors concluded that ongoing spontaneous activity is the key factor that determines the degree of long-term potentiation and long-term depression. The role of spontaneous activity in the induction of heterosynaptic LTD has been experimentally confirmed by Abraham et al. (2007). As predicted by the model, procaine infusion into the lateral path fibers, sufficient to transiently block neural activity in this pathway, prevented the induction of LTD in the lateral path following medial path high-frequency stimulation. Similar conclusions have been reached by Dong et al. (2008) who concluded that coincident activity of afferent pathways in the CA1 region can induce either LTP only or LTP/LTD depending on the experimental stimulation protocol and the state of hippocampal activity. The hippocampal EEG power was higher in urethane-anaesthetized rats and much higher in awake rats, which was correlated to the magnitude of LTD in following commissural pathway but not to that of LTP in preceding Schaffer pathway (Dong et al., 2008). CA1 pyramidal cells are principal excitatory cells in the hippocampal CA1 region. Ovoid cell bodies are located in the stratum pyramidale. A surface area of the pyramidal cells body is 465 ± 50 μm 2 and a diameter is ∼15 μm. CA1 pyramidal cell dendrites are classified into nine categories according to location,