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 (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.

Effect of temperature on FAD and NADH-derived signals and neurometabolic coupling in the mouse auditory and motor cortex

“…It is possible that during the equilibration time, cellular compensatory mechanisms could be triggered, which would be reflected in physiological and imaging measurements made in this study. Other investigators have used a more dynamic approach, measuring physiological changes that occur transiently after temperature change [16]. Interestingly, the results of the dynamic approach were generally similar to the results shown here.…”

Ion Channel Profile of TRPM8 Cold Receptors Reveals a Role of TASK-3 Potassium Channels in Thermosensation

“…In fact, closure of leak K + channels has been proposed as an alternative mechanism of cold temperature transduction in peripheral (Reid and Flonta, 2001; Viana et al, 2002) and central neurons (de la Pena et al, 2012). …”

Temperature influences neuronal activity and CO2/pH sensitivity of locus coeruleus neurons in the bullfrog,Lithobates catesbeianus

“…Coldactivated neurons have been studied in the dorsal root and the trigeminal ganglia for cold-sensory transduction (35,45) and in the preoptic area of the hypothalamus (POAH) for thermoregulation (6). Hippocampal neurons have also been shown to depolarize during cooling (13,49). Strikingly, all chemosensitive neurons in the LC of bullfrogs (83% of the LC neurons studied) displayed either cold-activation or warm-inhibition, while only ϳ15% of neurons studied within the trigeminal ganglion, ϳ7% of neurons in the dorsal root ganglion (35), and ϳ5% of neurons in the POAH (55) demonstrate cold-activation.…”

“…Inhibition of K ϩ conductance during cooling would cause depolarization and increased firing rate. Such a mechanism involving TREK-1 has been suggested to cause increased excitability in neurons of the hippocampus (13). Further, given that input resistance decreased in neurons that decreased firing rate with warming, the mechanism responsible for cold-activation is also probably responsible for warm-inhibition of chemosensitive LC neurons, e.g., closing a K ϩ channel during cooling and opening the same K ϩ channel during warming.…”