Passive synaptic normalization and input synchrony-dependent amplification of cortical feedback in thalamocortical neuron dendrites

Connelly, William M., Crunelli, Vincenzo ORCID: https://orcid.org/0000-0001-7154-9752 and Errington, Adam C. ORCID: https://orcid.org/0000-0002-2171-389X 2016. Passive synaptic normalization and input synchrony-dependent amplification of cortical feedback in thalamocortical neuron dendrites. Journal of Neuroscience 36 (13) , pp. 3735-3754. 10.1523/JNEUROSCI.3836-15.2016

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Abstract

Thalamocortical neurons have thousands of synaptic connections from layer VI corticothalamic neurons distributed across their dendritic trees. Although corticothalamic synapses provide significant excitatory input, it remains unknown how different spatial and temporal input patterns are integrated by thalamocortical neurons. Using dendritic recording, 2-photon glutamate uncaging, and computational modeling, we investigated how rat dorsal lateral geniculate nucleus thalamocortical neurons integrate excitatory corticothalamic feedback. We find that unitary corticothalamic inputs produce small somatic EPSPs whose amplitudes are passively normalized and virtually independent of the site of origin within the dendritic tree. Furthermore, uncaging of MNI glutamate reveals that thalamocortical neurons have postsynaptic voltage-dependent mechanisms that can amplify integrated corticothalamic input. These mechanisms, involving NMDA receptors and T-type Ca2+ channels, require temporally synchronous synaptic activation but not spatially coincident input patterns. In hyperpolarized thalamocortical neurons, T-type Ca2+ channels produce nonlinear amplification of temporally synchronous inputs, whereas asynchronous inputs are not amplified. At depolarized potentials, the input–output function for synchronous synaptic input is linear but shows enhanced gain due to activity-dependent recruitment of NMDA receptors. Computer simulations reveal that EPSP amplification by T-type Ca2+ channels and NMDA receptors occurs when synaptic inputs are either clustered onto individual dendrites or when they are distributed throughout the dendritic tree. Consequently, postsynaptic EPSP amplification mechanisms limit the “modulatory” effects of corticothalamic synaptic inputs on thalamocortical neuron membrane potential and allow these synapses to act as synchrony-dependent “drivers” of thalamocortical neuron firing. These complex thalamocortical input–output transformations significantly increase the influence of corticothalamic feedback on sensory information transfer.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Biosciences
Subjects:	R Medicine > R Medicine (General)
Additional Information:	This is an Open Access article distributed under the terms of the Creative Commons Attribution License Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Publisher:	Society for Neuroscience
ISSN:	1529-2401
Funders:	Wellcome Trust
Date of First Compliant Deposit:	22 April 2016
Date of Acceptance:	13 January 2016
Last Modified:	08 May 2023 20:21
URI:	https://orca.cardiff.ac.uk/id/eprint/89786

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