The role of spike blocking as spike-timing-dependent

plasticity mechanism

Eleftheria Kyriaki Pissadaki Computational Biology LaboratoryInstitute of Molecular Biology and Biotechnology

Outline

• Introduction

• Objectives

• Methods

• Preliminary Results

• Future Plan

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

Introduction

• CA1 is a sub region of hippocampus

• It is a component of the Hippocampal Network: The hippocampus forms a principally uni-directional network

Introduction

Introduction

• CA1 pyramidal cell is the principal cell of the region

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

Compartmental Model CA1 neuron

Compartmental model of circuits

1 dendrite + 1 spine

Zador et al. 1992We use NEURON written by Mike Hines

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

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

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

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

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.

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.