Postsynaptic mechanisms govern the differential excitation of cortical neurons by thalamic inputs.
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.
Hull
Court
C
Neurobiology Section, Division of Biology, School of Medicine, University of California, San Diego, La Jolla, California 92093-0634, USA.
Isaacson
Jeffry S
JS
Scanziani
Massimo
M
D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D025341:Principal Component Analysis; D011724:Pyridazines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D013003:Somatosensory Cortex / Q000166:cytology*; D013324:Strontium / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013788:Thalamus / Q000502:physiology*; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D011724:Pyridazines; D016194:Receptors, N-Methyl-D-Aspartate; C049853:gabazine; D002118:Calcium; D013324:Strontium