title: The influence of cold temperature on cellular excitability of hippocampal networks.
abstract: The hippocampus plays an important role in short term memory, learning and spatial navigation. A characteristic feature of the hippocampal region is its expression of different electrical population rhythms and activities during different brain states. Physiological fluctuations in brain temperature affect the activity patterns in hippocampus, but the underlying cellular mechanisms are poorly understood. In this work, we investigated the thermal modulation of hippocampal activity at the cellular network level. Primary cell cultures of mouse E17 hippocampus displayed robust network activation upon light cooling of the extracellular solution from baseline physiological temperatures. The activity generated was dependent on action potential firing and excitatory glutamatergic synaptic transmission. Involvement of thermosensitive channels from the transient receptor potential (TRP) family in network activation by temperature changes was ruled out, whereas pharmacological and immunochemical experiments strongly pointed towards the involvement of temperature-sensitive two-pore-domain potassium channels (K(2P)), TREK/TRAAK family. In hippocampal slices we could show an increase in evoked and spontaneous synaptic activity produced by mild cooling in the physiological range that was prevented by chloroform, a K(2P) channel opener. We propose that cold-induced closure of background TREK/TRAAK family channels increases the excitability of some hippocampal neurons, acting as a temperature-sensitive gate of network activation. Our findings in the hippocampus open the possibility that small temperature variations in the brain in vivo, associated with metabolism or blood flow oscillations, act as a switch mechanism of neuronal activity and determination of firing patterns through regulation of thermosensitive background potassium channel activity.
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Alicante, Spain. elvirap@umh.es
authors.forename: Elvira
authors.initials: E
authors.lastname: de la Peña
authors.forename: Annika
authors.initials: A
authors.lastname: Mälkiä
authors.forename: Hugo
authors.initials: H
authors.lastname: Vara
authors.forename: Rebeca
authors.initials: R
authors.lastname: Caires
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Ballesta
authors.forename: Carlos
authors.initials: C
authors.lastname: Belmonte
authors.forename: Felix
authors.initials: F
authors.lastname: Viana
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003080:Cold Temperature; D005071:Evoked Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009415:Nerve Net / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: C503433:Kcnk4 protein, mouse; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D018698:Glutamic Acid; D013779:Tetrodotoxin