title: Self-regulation of adult thalamocortical neurons.
abstract: The thalamus acts as a conduit for sensory and other information traveling to the cortex. In response to continuous sensory stimulation in vivo, the firing rate of thalamocortical neurons initially increases, but then within a minute firing rate decreases and T-type Ca(2+) channel-dependent action potential burst firing emerges. While neuromodulatory systems could play a role in this inhibitory response, we instead report a novel and cell-autonomous inhibitory mechanism intrinsic to the thalamic relay neuron. Direct intracellular stimulation of thalamocortical neuron firing initially triggered a continuous and high rate of action potential discharge, but within a minute membrane potential (Vm) was hyperpolarized and firing rate to the same stimulus was decreased. This self-inhibition was observed across a wide variety of thalamic nuclei, and in a subset firing mode switched from tonic to bursting. The self-inhibition resisted blockers of intracellular Ca(2+) signaling, Na(+)-K(+)-ATPases, and G protein-regulated inward rectifier (GIRK) channels as implicated in other neuron subtypes, but instead was in part inhibited by an ATP-sensitive K(+) channel blocker. The results identify a new homeostatic mechanism within the thalamus capable of gating excitatory signals at the single-cell level.
authors.affiliation: Departments of Neurology and Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, Center for Life Science, Boston, Massachusetts;
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kasten
authors.affiliation: Departments of Neurology and Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, Center for Life Science, Boston, Massachusetts; Program in Neuroscience, Harvard Medical School, Boston, Massachusetts; and Children's Hospital Boston Intellectual and Developmental Disabilities Research Center, Children's Hospital Boston, Boston, Massachusetts mpanders@bidmc.harvard.edu.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Anderson
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013788:Thalamus / Q000187:drug effects / Q000502:physiology*; D046509:Tissue Culture Techniques
chemical_list: C498197:Cacna1g protein, mouse; D020747:Calcium Channels, T-Type; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D054086:KATP Channels; D018377:Neurotransmitter Agents; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D002118:Calcium
keywords: KATP channel; excitability; thalamus