Energy Demand of Synaptic Transmission at the Hippocampal Schaffer-Collateral Synapse

Abstract

Neuroenergetic models of synaptic transmission predicted that energy demand is highest for action potentials (APs) and postsynaptic ion fluxes, whereas the presynaptic contribution is rather small. Here, we addressed the question of energy consumption at Schaffer-collateral synapses. We monitored stimulus-induced changes in extracellular potassium, sodium, and calcium concentration while recording partial oxygen pressure (pO 2 ) and NAD(P)H fluorescence. Blockade of postsynaptic receptors reduced ion fluxes as well as pO 2 and NAD(P)H transients by B50%. Additional blockade of transmitter release further reduced Na þ , K þ , and pO 2 transients by B30% without altering presynaptic APs, indicating considerable contribution of Ca 2 þ -removal, transmitter and vesicle turnover to energy consumption. Keywords: action potential; brain slice; electrophysiology; energy metabolism; evoked potentials; hippocampus INTRODUCTION Energy limitations determine the computational power and speed of neuronal systems. 1 Therefore, it is of critical importance to identify the energy demand associated with processes involved in neuronal computing such as synaptic transmission and action potential (AP) firing. Theoretical calculations on the basis of current kinetics in squid giant axons suggested that APs and postsynaptic ion fluxes rather than presynaptic processes determine energy consumption. 1,2 More recently, energy efficient AP generation and conduction was described in hippocampal mossy fibers. 3--5 Recalculating the energy need for APs suggests larger contribution of postsynaptic and presynaptic processes and transmitter uptake to the energy demand of synaptic transmission. 6,7 The authors predicted that in cerebral cortex, 50% of signaling associated energy is spent on restoration of ion fluxes at postsynaptic glutamate receptors, 21% is spent on APs, 20% on resting potentials, 5% and 4% on presynaptic transmitter release and transmitter recycling, respectively. However, such numbers have to be calculated or determined experimentally for each brain area in question as synaptic densities, receptor types, and ion channel expression differ for each particular signaling pathway. Journal of Cerebral BloodHere, we sought to determine the contribution of pre-and postsynaptic processes to changes in energy metabolism associated with glutamatergic and GABAergic transmission at the hippocampal Schaffer-collateral synapse that represents one of the best-studied connections in the archicortex. We monitored stimulus-induced changes in extracellular potassium, sodium, and calcium concentrations ([K þ ] o , [Na þ ] o , [Ca 2 þ ] o ) while recording tissue partial oxygen pressure (pO 2 ) and metabolism-related NAD(P)H transients. The energy demand of each single component of synaptic transmission

High-Probability Neurotransmitter Release Sites Represent an Energy-Efficient Design

“…Yet, even if correct only in order of magnitude, we would conclude that the presynaptic terminal consumes ~1% of the NMJ energy budget. This proportion contrasts starkly with estimates at mammalian central synapses, at which presynaptic energy demands are ~30% of the total synaptic signaling cost [16, 17]. If presynaptic terminals only consume 1% of the NMJ energy budget we suggest that the ability to locomote without fatigue ultimately conferred a greater selection advantage than the energy saved by an efficient terminal, and that as a result low P AZ release sites persisted at the expense of high P AZ sites.…”

“…Initially, total energy demand can be approximated as the sum of the cost of SV release and recycling, and the cost on Ca 2+ extrusion [17, 29]:…”

“…Multiple calcium ions (Ca 2+ ) are required to trigger the release of neurotransmitters and this generates a steep dependency of P AZ on Ca 2+ entry, described as a sigmoid function [15]. As the cost of Ca 2+ removal is one of the primary costs of the presynaptic terminal [16, 17] we might expect that energy efficiency will be optimized when neurotransmitter release is maximized relative to Ca 2+ entry. This point does not occur until gains in neurotransmitter release become marginal relative to Ca 2+ entry, i.e.…”

Minimizing photodecomposition of flavin adenine dinucleotide fluorescence by the use of pulsed LEDs

“…Simultaneous [K + ] o and field potential measurements were performed using double‐barrelled ion‐sensitive microelectrodes built according to the protocol described in Liotta et al . (). The Potassium Ionophore I 60031 (Fluka, Buchs, Switzerland) was used accordingly.…”

Sugar for the brain: the role of glucose in physiological and pathological brain function

“…It has been suggested that action potentials have been rendered highly efficient through evolution [10], and thus most of the energy consumed in the brain is used on synaptic activity [3, 10, 11]. The human cortex alone requires approximately 3×10 23 ATP/s/m 3 [1], and the energy expenditure to release one synaptic vesicle is roughly calculated to be 1.64×10 5 molecules ATP [3].…”