Format

Send to

Choose Destination
J Neurosci. 2016 Mar 30;36(13):3735-54. doi: 10.1523/JNEUROSCI.3836-15.2016.

Passive Synaptic Normalization and Input Synchrony-Dependent Amplification of Cortical Feedback in Thalamocortical Neuron Dendrites.

Author information

1
Neuroscience Division, School of Biosciences, Cardiff University, Cardiff CF10 3AX, United Kingdom, Eccles Institute of Neuroscience, The John Curtin School of Medical Research, Australian National University, Canberra City, Australian Capital Territory 2600, Australia.
2
Neuroscience Division, School of Biosciences, Cardiff University, Cardiff CF10 3AX, United Kingdom, Department of Physiology and Biochemistry, University of Malta, Msida MSD 2080, Malta.
3
Neuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff CF24 4HQ, United Kingdom, and erringtonac@cardiff.ac.uk.

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 Ca(2+)channels, require temporally synchronous synaptic activation but not spatially coincident input patterns. In hyperpolarized thalamocortical neurons, T-type Ca(2+)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 Ca(2+)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.

SIGNIFICANCE STATEMENT:

Neurons in first-order thalamic nuclei transmit sensory information from the periphery to the cortex. However, the numerically dominant synaptic input to thalamocortical neurons comes from the cortex, which provides a strong, activity-dependent modulatory feedback influence on information flow through the thalamus. Here, we reveal how individual quantal-sized corticothalamic EPSPs propagate within thalamocortical neuron dendrites and how different spatial and temporal input patterns are integrated by these cells. We find that thalamocortical neurons have voltage- and synchrony-dependent postsynaptic mechanisms, involving NMDA receptors and T-type Ca(2+)channels that allow nonlinear amplification of integrated corticothalamic EPSPs. These mechanisms significantly increase the responsiveness of thalamocortical neurons to cortical excitatory input and broaden the "modulatory" influence exerted by corticothalamic synapses.

KEYWORDS:

NMDA receptor; T-type calcium channel; dendritic integration; passive normalization; thalamocortical

PMID:
27030759
PMCID:
PMC4812133
DOI:
10.1523/JNEUROSCI.3836-15.2016
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central Icon for ModelDB
Loading ...
Support Center