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 (K2P), 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 K2P 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.
Highlights
Homeothermic animals maintain a core temperature of 36– 37uC within narrow ranges
We found a novel, unexpected increase in network activity mediated by closure of temperature-sensitive two-pore-domain potassium channels (KCNK), TREK/TRAAK channels [24,25,26,27]
The synaptic currents consisted of brief excitatory and/or inhibitory miniature postsynaptic currents
Summary
Homeothermic animals maintain a core temperature of 36– 37uC within narrow ranges. Mammalian brain temperatures experience fluctuations of 1–3uC during physiological activities, such as exercise and feeding or in response to stressful stimuli [1,2]. Even more pronounced changes in brain temperature occur during anesthesia or administration of psychoactive drugs [3]. Changes in brain temperature have dramatic effects on neural function. Hyperthermia induces epileptiform-like activity in hippocampal slices [4,5] and fever greatly increases the likelihood of epileptic discharges in children [6]. A reduction in brain temperature precedes the onset of sleep, a brain state exhibiting a variety of characteristic activity patterns [7,8]
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