Mitochondria as ATP consumers: Cellular treason in anoxia

In anoxia, mitochondria change from being ATP producers to potentially powerful ATP consumers. This change occurs, because the mitochondrial F1F0-ATPase begins to hydrolyze ATP to avoid the collapse of the proton motive force. Species that can survive prolonged periods of O2 lack must limit such ATP use; otherwise, this process would dominate glycolytic metabolism and threaten ATP delivery to essential ATP-consuming processes of the cell (e.g., ion-motive ATPases). There are two ways to limit ATP hydrolysis by the F1F0-ATPase, namely (i) reduction of the proton conductance of the mitochondrial inner membrane and (ii) inhibition of the enzyme. We assessed these two possibilities by using intact mitochondria isolated from the skeletal muscle of anoxia-tolerant frogs. Our results show that proton conductance is unaltered between normoxia and anoxia. However, ATP use by the F1F0-ATPase is limited in anoxia by a profound inhibition of the enzyme. Even so, ATP use by the F1F0-ATPase might account for ≈9% of the ATP turnover in anoxic frog skeletal muscle.

A model of long-term memory storage in the cerebellar cortex: A possible role for plasticity at parallel fiber synapses onto stellate/basket interneurons

By evoking changes in climbing fiber activity, movement errors are thought to modify synapses from parallel fibers onto Purkinje cells (pf*Pkj) so as to improve subsequent motor performance. Theoretical arguments suggest there is an intrinsic tradeoff, however, between motor adaptation and long-term storage. Assuming a baseline rate of motor errors is always present, then repeated performance of any learned movement will generate a series of climbing fiber-mediated corrections. By reshuffling the synaptic weights responsible for any given movement, such corrections will degrade the memories for other learned movements stored in overlapping sets of synapses. The present paper shows that long-term storage can be accomplished by a second site of plasticity at synapses from parallel fibers onto stellate/basket interneurons (pf*St/Bk). Plasticity at pf*St/Bk synapses can be insulated from ongoing fluctuations in climbing fiber activity by assuming that changes in pf*St/Bk synapses occur only after changes in pf*Pkj synapses have built up to a threshold level. Although climbing fiber-dependent plasticity at pf*Pkj synapses allows for the exploration of novel motor strategies in response to changing environmental conditions, plasticity at pf*St/Bk synapses transfers successful strategies to stable long-term storage. To quantify this hypothesis, both sites of plasticity are incorporated into a dynamical model of the cerebellar cortex and its interactions with the inferior olive. When used to simulate idealized motor conditioning trials, the model predicts that plasticity develops first at pf*Pkj synapses, but with additional training is transferred to pf*St/Bk synapses for long-term storage.