1. The role of spike blocking as spike-timing-dependent plasticity mechanism Eleftheria Kyriaki Pissadaki Computational Biology Laboratory Institute of Molecular Biology and Biotechnology

2. Outline Introduction Objectives Methods Preliminary Results Future Plan

3. Introduction Hippocampus is a brain structure important for learning and memory processes But, what kind of learning and what type of memory? Since information processing and memory formation is shared by several brain areas, hippocampus may act as a part of this functional system

4. Introduction CA1 is a sub region of hippocampus It is a component of the Hippocampal Network: The hippocampus forms a principally uni- directional network

5. Introduction

6. CA1 pyramidal cell is the principal cell of the region

7. Spike-timing-dependent plasticity The modification of synaptic strengths in many systems depends on the precise timing of pre- and post-synaptic spikes If a pre-synaptic spike precedes a post-synaptic spike within a window of tens of milliseconds, then the synapse potentiates If a pre-synaptic spike arrives after a post-synaptic spike within a similar window, the synapse depresses It is worth saying that the signaling mechanism that underlines the previous phenomenon is not fully understood

8. Compartmental Model CA1 neuron Compartmental model of circuits 1 dendrite + 1 spine Zador et al. 1992 We use NEURON written by Mike Hines

9. Compartmental Model The cell has been divided into layers, according to Megias et al research paper, in order to simulate the different input patterns that its layer receives

10. Objectives The investigation of the effect of patterned stimulation in different layers of the model cell on the neuron’s firing properties The identification of membrane mechanisms that may support STDP The biological interpretation of STDP results in learning and memory processes of hippocampus Predictions and evaluations concerning the stimulated paths and whether these are carriers of a specific learning form such as consolidation, retrieval or acquisition

11. Preliminary results Investigating the model’s behavior in relation to recent experimental findings. Based on electrophysiological recordings, the output of CA1 pyramidal cells is modulated in an input pattern-dependent manner by activation of the direct pathway from entorhinal cortex

12. Preliminary results Delivering two stimuli: a suprathreshold Burst Stimulation at Schaffer Collateral and a below-threshold stimulation at Stratum Lacunosum Moleculare. The Spike-Blocking efficacy is produced

13. Preliminary results The corresponding behavior identified in this study is a spike- blocking effect that is related with the time-difference of stimuli in stratum lacunosum moleculare (SLM) and stratum radiatum, and additionally with the number of stimuli in the SLM burst. The above activity is attributed mainly to GABAb influence Dendritic currents could compensate and mediate the observed waveforms (Ih or fAHP) Further investigation about the influence of different time windows and stimulation patterns in the generation of this phenomenon.

14. Future plan Analysis of spike-timing-dependent plasticity in different combinations of layers The biological meaning of this silencing effect dispatched by the temporoammonic (TA) pathway has been proposed to be a switch from encoding to retrieval memory. Recently literature confirms that TA is a pathway responsible for memory consolidation (Remondes_Schuman, 2004). interest will be paid in the direction of learning specificity in other pathways Following the investigation of STDP mechanisms in the normal CA1 model cell, the next target will be to extrapolate the findings into a degenerated state of the model neuron as this degeneration is imposed after the persistent exposure to the stress hormones which are secreted by the adrenal cortex after stressful events. The long term goal is to identify STDP defects in the stressed neuron that may explain the reduction in learning and memory associated with chronic stress.