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Mechanisms of rhythm generation in cultured neural networks: roles of INaP, ICAN, cholinergic neurons and endogenous electrical fields

English title Mechanisms of rhythm generation in cultured neural networks: roles of INaP, ICAN, cholinergic neurons and endogenous electrical fields
Applicant Streit Jürg
Number 140754
Funding scheme Project funding (Div. I-III)
Research institution Institut für Physiologie Medizinische Fakultät Universität Bern
Institution of higher education University of Berne - BE
Main discipline Neurophysiology and Brain Research
Start/End 01.04.2012 - 30.09.2015
Approved amount 302'178.00
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Keywords (6)

neural networks; pacemaker currents; oscillations; rhythm generation; cholinergic neurons; electrical fields

Lay Summary (English)

Lead
Lay summary
Practically all functions of the central nervous system emerge on the level of networks of neurons. In the mammalian brain, such networks are interacting in a complex and distributed way, making their analysis difficult. Emerging properties for the generation of population responses in defined small networks are therefore better investigated in simplified systems like neuronal cultures. A key function of these networks is the generation of rhythmic activity. In the spinal cord, such activity patterns are used to drive repetitive movements for locomotion. In the cortex, rhythms are involved in motor control, perception and memory processes. Our project is involved in studying the mechanisms of rhythm generation in neural networks in organotypic explant cultures. We are doing this by combining extracellular electrical recordings from many sites in the culture to investigate the network level with intracellular electrical recordings from single nerve cells to investigate the cellular level. Multisite recordings are realized using multielectrode arrays (MEAs), intracellular recordings are realized using whole cell patch clamp. Searching for pacemaker currents in spinal cord networks, we have shown in previous work that a persistent sodium current (INaP) has a major role in the generation of spontaneous rhythmic activity. In the first part of the actual project, we want to extend this work by investigating an additional candidate for a pacemaker current , the calcium-activated cation current (ICAN), using pharmacological tools. In the second part of the project we will investigate the role of cholinergic neurons in rhythm generation. In the last part we want to investigate feedback effects of activity-dependent small electrical fields on rhythm generation in cultures of the cerebral cortex. Revealing the sources of spontaneous rhythmic activity is an important step to understand normal and abnormal functions of neuronal networks.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Investigating functional regeneration in organotypic spinal cord co-cultures grown on multi-electrode arrays
Heidemann Martina, Streit Jürg, Tscherter Anne (2015), Investigating functional regeneration in organotypic spinal cord co-cultures grown on multi-electrode arrays, in Journal of Visualized Experiments, 2015(103), 1-10.
FUNCTIONAL REGENERATION OF INTRASPINAL CONNECTIONS IN A NEW IN VITRO MODEL
Heidemann M., Streit J., Tscherter A. (2014), FUNCTIONAL REGENERATION OF INTRASPINAL CONNECTIONS IN A NEW IN VITRO MODEL, in NEUROSCIENCE, 262, 40-52.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
IBRO 9th World Congress 2015 Poster Rhythm generation in organotypic rat spinal cord cultures is based on cooperation between INaP and ICAN. 10.07.2015 Rio de Janeiro, Brazil Streit Jürg; Heidemann Martina;
FENS Forum of Neuroscience 2014 Poster Spinal cord slices in culture functionally connect via propriospinal pathways. 09.07.2014 Milano, Italy Streit Jürg; Heidemann Martina;
FENS Forum of Neuroscience 2014 Poster The role of calcium-activated non-selective cation currents for rhythm generation in spinal cord cultures. 09.07.2014 Milano, Italy Streit Jürg; Heidemann Martina;
SSN Annual Meeting 2014 Poster Functional regeneration of intraspinal connections in vitro. 25.01.2014 Bern, Switzerland Heidemann Martina; Streit Jürg;
Meeting of the Swiss Physiological Society 2012 Poster Assessing spinal cord regeneration in a petri dish. 13.09.2012 Fribourg, Switzerland Heidemann Martina; Streit Jürg;
FENS Forum of Neuroscience 2012 Poster Functional recovery In the spinal cord In vitro: a new model to prescreen potential treatments. 15.07.2012 Barcelona, Spain Streit Jürg; Heidemann Martina;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Nacht der Forschung Uni Bern German-speaking Switzerland 2014

Associated projects

Number Title Start Funding scheme
120327 Emergent properties and rhythm generation in cultured neural networks 01.04.2008 Project funding (Div. I-III)

Abstract

1.1 Rationale: During the last years our group has investigated the mechanisms involved in the generation of rhythmic activity in organotypic slice cultures in vitro based on the properties of the cultured neurons and their innate rules of network formation. In this project we want to continue this approach to test the hypothesis that the calcium activated cation current (ICAN), together with the persistent inward current (INaP) is critically involved in rhythm generation in spinal cord and in cortical networks. Furthermore we want to investigate the contribution of motoneurons to rhythm generation in spinal cord networks and of cholinergic interneurons in cortical networks. Finally, we want to investigate the role of endogenous electrical fields on rhythm generation in cortical networks.1.2 Methods: The project will be based on a combination of extracellular recordings with multielectrode arrays (MEAs) with 68 electrodes and intracellular recordings with patch clamp from slice cultures. For this we plan to upgrade a second setup for such combined measurements from cultures with GFP labelled neurons. In addition, we want to develop the application of activity-dependent extracellular electrical fields with MEA electrodes. 1.3 Specific experiments: 1. Sub-project: Role of INaP and ICAN for rhythm generation in longitudinal spinal cord slice cultures: We want to investigate the roles of INaP and ICAN as pacemaker currents for rhythm generation in cultures of longitudinal ventral horn slices from lumbar spinal cord of embryonic rats. 2. Sub-project: Role of motoneurons for rhythm generation in longitudinal spinal cord cultures: We want to study the role of motoneurons for rhythm generation by measuring in parallel the activity of spinal cord networks and of defined motoneurons in cultures of longitudinal ventral horn slices from lumbar spinal cord of neonatal ChAT(BAC)-eGFP mice containing GFP-labelled cholinergic neurons. 3. Sub-project: Role of INaP and ICAN for rhythm generation in cortical cultures: We want to investigate the roles of INaP and ICAN as pacemaker currents for rhythm generation in cortical slice cultures from neonatal GAD67- GFP mice containing GFP-labelled GABAergic interneurons. 4. Sub-project: Role of cortical cholinergic interneurons for rhythm generation in cortical circuits: We want to study the role of cortical cholinergic interneurons for rhythm generation by measuring in parallel the activity of cortical networks and of defined cholinergic interneurons in cortical cultures of neonatal ChAT(BAC)-eGFP mice. 5. Sub-project: Role endogenous electrical fields for rhythm generation in cortical circuits: Using the MEA electrodes, we want to apply small “natural” electrical fields to cortical cultures from neonatal GAD67- GFP mice and investigate whether spike rate during fast oscillations is influenced by the fields. 1.4 Significance: Understanding cellular and sub-cellular mechanisms of rhythm generation by neuronal networks is important for the development of strategies for network activation after damage and for preventing over-activation as for example during epileptogenesis. Understanding electrical field effects is important for the evaluation of possible effects of exogenous fields that are for example applied during transcranial magnetic stimulation (TMS).
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