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Differential learning rules at cortical synapses: A study of synaptic plasticity at multiple input sites

Applicant Nevian Thomas
Number 118395
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 01.01.2008 - 30.06.2010
Approved amount 335'000.00
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Keywords (10)

synaptic plasticity; spike-timing dependent plasticity; two-photon microscopy; dendrite; long-term potentiation; LTP; long-term depression; LTD; calcium; spine

Lay Summary (English)

Lead
Lay summary
Synaptic plasticity is thought to be the cellular correlate for the formation of memory traces in the brain. Recently, spike-timing dependent plasticity, which describes the up- and down regulation of the connection strength between two neurons, has gained increased interest as a plausible physiological mechanism for the activity-dependent modification of synaptic strength. It might be fundamental for circuit refinement, map plasticity and the explanation of higher brain functions. It is not clear if spike-timing dependent plasticity is a universal learning rule based on simple biophysical mechanisms. The molecular signalling pathways involved are quite diverse and apparently use-dependent. The fundamental question is what determines the molecular machinery at a synaptic contact that translates electrical activity into a change in synaptic strength.Therefore, two-photon fluorescence microscopy will be combined with electrophysiological methods to record the changes in synaptic transmission strength in neocortical brain slice preparations. Focal multi-site stimulation of many synaptic contacts by axonal tracking and laser stimulation will allow determining the specific learning rules at each input site simultaneously. The results of this study will be relevant for our understanding of synaptic plasticity on the single cell level and the formation of memory traces in neuronal networks. They will be fundamental to test current hypothesises about the activity dependent refinement of neuronal networks and signal processing in the brain.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Activity pattern-dependent long-term potentiation in neocortex and hippocampus of GluA1 (GluR-A) subunit-deficient mice
Frey Marco C., Sprengel Rolf, Nevian Thomas (2009), Activity pattern-dependent long-term potentiation in neocortex and hippocampus of GluA1 (GluR-A) subunit-deficient mice, in Journal of Neuroscience, 29(17), 5587-5596.
Synaptic integration in tuft dendrites of layer 5 pyramidal neurons: a new unifying principle.
Larkum Matthew E, Nevian Thomas, Sandler Maya, Polsky Alon, Schiller Jackie (2009), Synaptic integration in tuft dendrites of layer 5 pyramidal neurons: a new unifying principle., in Science, 325(5941), 756-60.

Abstract

Background. Synaptic plasticity is thought to be the cellular correlate for the formation of memory traces in the brain. Recently, spike-timing dependent plasticity has gained increased interest as a plausible physiological mechanism for the activity-dependent modification of synaptic strength. It might be fundamental for circuit refinement, map plasticity and the explanation of higher brain functions. It is not clear if spike-timing dependent plasticity is a universal learning rule based on simple biophysical mechanisms. The molecular signalling pathways involved are quite diverse and apparently use-dependent. The fundamental question is what determines the molecular machinery at a synaptic contact that translates electrical activity into a change in synaptic strength.Specific Aims. (1) The influence of active dendritic properties, which can result in the generation of local dendritic spikes, on changes in synaptic strength will be studied. They will have an important impact on the local learning rules. (2) A particular mechanism of long-term depression depending on presynaptic NMDA receptors will be studied and the biophysical signalling cascades will be elucidated. (3) The diversity of synaptic learning rules will be studied in a single neuron to answer the question if a cellular learning rule is universal for a given cell type or if a cell employs multiple plasticity mechanisms. (4) In this context the influence of neuromodulators on spike-timing dependent plasticity will be studied. (5) Memories might not only be stored in the synaptic weight but also in the specific pattern of connectivity. Spike-timing dependent rewiring of neuronal networks will be investigated in this respect. (6) The experimental data acquired during the course of the proposal period will be implemented into model neurons to understand the transformation from electrical activity into synaptic plasticity in more detail.Methods. Two-photon fluorescence microscopy will be combined with electrophysiological methods to record the changes in synaptic transmission strength in neocortical brain slice preparations. Focal multi-site stimulation of many synaptic contacts by axonal tracking and laser stimulation will allow determining the specific learning rules at each input site simultaneously. Combination with a novel approach to patch-clamp recordings from fine dendritic structures it will even be possible to measure the membrane potential and changes in synaptic strength close to a synaptic contact.Expected Value of the Proposed Project. The expected results of the proposed project will be highly relevant for our understanding of synaptic plasticity on the single cell level and the formation of memory traces in neuronal networks. They will be fundamental to refine current hypothesises about the activity dependent refinement of neuronal networks and signal processing in the brain. By studying the diversity of synaptic plasticity novel fundamental principles of a diverse set of learning rules might nevertheless be revealed.
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