Postsynaptic Mechanisms Govern the Differential Excitation of Cortical Neurons by Thalamic Inputs

Neurobiology Section, Division of Biology, School of Medicine, University of California, San Diego, La Jolla, California 92093-0634, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 08/2009; 29(28):9127-36. DOI: 10.1523/JNEUROSCI.5971-08.2009
Source: PubMed


Thalamocortical (TC) afferents relay sensory input to the cortex by making synapses onto both excitatory regular-spiking principal cells (RS cells) and inhibitory fast-spiking interneurons (FS cells). This divergence plays a crucial role in coordinating excitation with inhibition during the earliest steps of somatosensory processing in the cortex. Although the same TC afferents contact both FS and RS cells, FS cells receive larger and faster excitatory inputs from individual TC afferents. Here, we show that this larger thalamic excitation of FS cells occurs via GluR2-lacking AMPA receptors (AMPARs), and results from a fourfold larger quantal amplitude compared with the thalamic inputs onto RS cells. Thalamic afferents also activate NMDA receptors (NMDARs) at synapses onto both cells types, yet RS cell NMDAR currents are slower and pass more current at physiological membrane potentials. Because of these synaptic specializations, GluR2-lacking AMPARs selectively maintain feedforward inhibition of RS cells, whereas NMDARs contribute to the spiking of RS cells and hence to cortical recurrent excitation. Thus, thalamic afferent activity diverges into two routes that rely on unique complements of postsynaptic AMPARs and NMDARs to orchestrate the dynamic balance of excitation and inhibition as sensory input enters the cortex.

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    • "± 13.9 pA, holding potential = −70 mV). The difference was significant (paired t test, P < 0.05, n = 7), and consistent with recent reports (Gabernet et al. 2005; Cruikshank et al. 2007; Hull et al. 2009). By placing two independent stimulating electrodes , we could estimate conduction velocities (CV) for thalamocortical axons innervating inhibitory and excitatory cells. "
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    • "Postsynaptic mechanisms may include differences in the subunit composition of the glutamate receptors. For instance, interneurons, in contrast to PNs, generally exhibit a significant proportion of Ca 2+ -permeable GluA2- lacking AMPA receptors (CP-AMPARs) (Angulo et al., 1997; Hull et al., 2009; Zaitsev et al., 2011) that possess specific biophysical properties, including Ca 2+ permeability , current rectification at positive membrane voltages, a higher single-channel conductance, and faster kinetics (Geiger et al., 1995; Feldmeyer et al., 1999; Fig. 9 "
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    ABSTRACT: Properties of excitatory synaptic responses in fast-spiking interneurons (FSIs) and pyramidal neurons (PNs) are different; however, the mechanisms and determinants of this diversity have not been fully investigated. In the present study, voltage-clamp recording of miniature excitatory post-synaptic currents (mEPSCs) was performed of layer 2-3 FSIs and PNs in the medial prefrontal cortex of rats aged 19-22 days. The average mEPSCs in the FSIs exhibited amplitudes that were two times larger than those of the PNs and with much faster rise and decay. The mEPSC amplitude distributions in both cell types were asymmetric and in FSIs, the distributions were more skewed and had two-times larger coefficients of variation than in the PNs. In PNs but not in FSIs, the amplitude distributions were fitted well by different skewed unimodal functions that have been used previously for this purpose. In the FSIs, the distributions were well approximated only by a sum of two such functions, suggesting the presence of at least two subpopulations of events with different modal amplitudes. According to our estimates, two-thirds of the mEPSCs in FSIs belong to the high-amplitude subpopulation, and the modal amplitude in this subpopulation is approximately two times larger than that in the low-amplitude subpopulation. Using different statistical models, varying binning size, and data subsets, we confirmed the robustness and consistency of these findings. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
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    • "Nevertheless, in support of the idea that NMDAR antagonists are unlikely to produce FS neuron-mediated disinhibition, disynaptic inhibitory postsynaptic potential (IPSP) recruitment is NMDAR-independent in somatosensory cortex (Ling and Benardo, 1995; Hull et al., 2009) and PFC (Rotaru et al., 2011), although it is NMDAR-dependent in hippocampal circuits (Ling and Benardo, 1995; Grunze et al., 1996). NMDAR-dependent disynaptic inhibition may be produced by NFS/PV-negative neurons, which have synapses with strong NMDAR contribution (Lamsa et al., 2007; Lu et al., 2007; Wang and Gao, 2009). "
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