The role of spike blocking as spike-timing-dependent plasticity mechanism Eleftheria Kyriaki...
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Transcript of The role of spike blocking as spike-timing-dependent plasticity mechanism Eleftheria Kyriaki...
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.