The role of spike blocking as spike-timing-dependent plasticity mechanism

1. The role of spike blocking as spike-timing-dependent plasticity mechanism Eleftheria Kyriaki Pissadaki Computational Biology LaboratoryInstitute 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. Introduction • 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 of circuits CA1 neuron 1 dendrite + 1 spine Zador et al. 1992 We use NEURON written by Mike Hines Compartmental Model

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.