Extended Data Fig. 4: Related to Fig. 2. Parameters and outputs of neuronal metabolic modeling.
From: Mitochondrial Ca2+ efflux controls neuronal metabolism and long-term memory across species
(A) Schematic of the computational model showing how activity-dependent Ca2+ influx elevates cytosolic and mitochondrial Ca2+, increasing ATP consumption and mitochondrial metabolism. Mitochondrial Ca2+ export is controlled by NCLX and Letm1 in control neurons, and mainly by NCLX in Letm1 KD. Ca2+ activates TCA cycle reactions, including PDP1-mediated boosting of PDHc activity. (B) Simulation of the metabolic expense of spiking. KANT is the change in the rate of adenine nucleotide translocator (ANT) caused by a neuronal spike. ANT exchanges cytosolic ADP for mitochondrial ATP. Ks = 1/1000 seconds. Spike-associated (dark red) and spike-independent (light red) metabolic cost are depicted. (C) Change in the mitochondrial fraction of ATP and ADP due a single neuronal spike. (D) Decay in free mitochondrial Ca2+ following 1AP (top) or 20AP at 20 Hz (bottom), modeled to be slower in Letm1 KD. (E) Simulation of activity-driven ATP dynamics in control and Letm1 KD in arbitrary units (a.u.).
