Propagation of synaptic temperature fluctuations by glutamateelectro-diffusion

Brain temperature is strongly regulated by cerebral blood flow and shows fluctuations in response to stimuli and neuroactive drugs. Cells in the nervous system not only detect environmental temperature changes through their unique temperature-sensitive molecular machineries but also muster an appropriate response to the temperature change to maintain their inherent functions. However, the mechanisms by which neurons produce, use and transfer heat are largely unknown. The focus of this study is the latter, namely how temperature gradients are transferred within the synaptic cleft, a process that can affect synaptic transmission by ultimately altering conductivity of post-synaptic ion channels. The dissolution of (charged or polar) neurotransmitters such as glutamate following release from presynaptic terminals within the extracellular fluid has been considered to be driven largely by diffusion. Furthermore, the electric fields of narrow synaptic clefts may also influence synaptic currents. However, how these processes causally relate to heat propagation remains poorly understood, mainly because events inside the cleft are beyond the powers of direct experimental observation. We use a non-equilibrium thermodynamical model comprised by a system of partial differential equations that describes the changes in intracleft temperature as a function of electrodiffusion of neurotransmitters. Numerical simulations suggest that transmitter release and propagation correspond to measurable thermal fluctuations ranging from tens to hundreds of mK within the cleft. The findings provide a plausible description for temperature changes during normal brain activity that are independent from those induced by blood circulation and provide correction-factors for temperature changes associated with diseases such as epilepsy and Parkinson’s