title: Delayed and Temporally Imprecise Neurotransmission in Reorganizing Cortical Microcircuits.
abstract: Synaptic neurotransmission is modified at cortical connections throughout life. Varying the amplitude of the postsynaptic response is one mechanism that generates flexible signaling in neural circuits. The timing of the synaptic response may also play a role. Here, we investigated whether weakening and loss of an entire connection between excitatory cortical neurons was foreshadowed in the timing of the postsynaptic response. We made electrophysiological recordings in rat primary somatosensory cortex that was undergoing experience-dependent loss of complete local excitatory connections. The synaptic latency of pyramid-pyramid connections, which typically comprise multiple synapses, was longer and more variable. Connection strength and latency were not correlated. Instead, prolonged latency was more closely related to progression of connection loss. The action potential waveform and axonal conduction velocity were unaffected, suggesting that the altered timing of neurotransmission was attributable to a synaptic mechanism. Modeling studies indicated that increasing the latency and jitter at a subset of synapses reduced the number of action potentials fired by a postsynaptic neuron. We propose that prolonged synaptic latency and diminished temporal precision of neurotransmission are hallmarks of impending loss of a cortical connection.
authors.affiliation: MRC Centre Neurodegeneration Research, King's College London, De Crespigny Park, London SE5 8AF, United Kingdom, and.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Barnes
authors.affiliation: MRC Centre Neurodegeneration Research, King's College London, De Crespigny Park, London SE5 8AF, United Kingdom, and.
authors.forename: Claire E
authors.identifier: http://orcid.org/0000-0002-4038-1501
authors.initials: CE
authors.lastname: Cheetham
authors.affiliation: MRC Centre Neurodegeneration Research, King's College London, De Crespigny Park, London SE5 8AF, United Kingdom, and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: MRC Centre Neurodegeneration Research, King's College London, De Crespigny Park, London SE5 8AF, United Kingdom, and.
authors.forename: Sophie H
authors.initials: SH
authors.lastname: Bennett
authors.affiliation: MRC Centre Neurodegeneration Research, King's College London, De Crespigny Park, London SE5 8AF, United Kingdom, and.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Albieri
authors.affiliation: Computer Vision Laboratory and.
authors.forename: Anne A
authors.identifier: http://orcid.org/0000-0002-6438-1979
authors.initials: AA
authors.lastname: Jorstad
authors.affiliation: Bio-EM facility, Centre of Interdisciplinary Electron Microscopy, EPFL, CH-1015 Lausanne, Switzerland.
authors.forename: Graham W
authors.initials: GW
authors.lastname: Knott
authors.affiliation: MRC Centre Neurodegeneration Research, King's College London, De Crespigny Park, London SE5 8AF, United Kingdom, and gerald.finnerty@kcl.ac.uk.
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Finnerty
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology* / Q000648:ultrastructure*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D005260:Female; D008297:Male; D009415:Nerve Net / Q000502:physiology* / Q000648:ultrastructure*; D009924:Organ Culture Techniques; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors
keywords: latency; neural code; plasticity; presynaptic; rewiring; synapse