Glutamine-to-glutamate ratio in the nucleus accumbens predicts effort-based motivated performance in humans

Substantial evidence implicates the nucleus accumbens in motivated performance, but very little is known about the neurochemical underpinnings of individual differences in motivation. Here, we applied 1H magnetic resonance spectroscopy (1H-MRS) at ultra-high-field in the nucleus accumbens and inquired whether levels of glutamate (Glu), glutamine (Gln), GABA or their ratios predict interindividual differences in effort-based motivated task performance. Given the incentive value of social competition, we also examined differences in performance under self-motivated or competition settings. Our results indicate that higher accumbal Gln-to-Glu ratio predicts better overall performance and reduced effort perception. As performance is the outcome of multiple cognitive, motor and physiological processes, we applied computational modeling to estimate best-fitting individual parameters related to specific processes modeled with utility, effort and performance functions. This model-based analysis revealed that accumbal Gln-to-Glu ratio specifically relates to stamina; i.e., the capacity to maintain performance over long periods. It also indicated that competition boosts performance from task onset, particularly for low Gln-to-Glu individuals. In conclusion, our findings provide novel insights implicating accumbal Gln and Glu balance on the prediction of specific computational components of motivated performance. This approach and findings can help developing therapeutic strategies based on targeting metabolism to ameliorate deficits in effort engagement

Synaptosome Bioenergetics and Calcium Handling: Aging Response

Synaptic function and the role of mitochondria inside nerve terminals can be studied by the isolation of an enriched fraction of synaptosomes, which consist in nerve ending particles that are formed during homogenization of brain tissue. Different procedures have been described for the isolation of an enriched fraction of synaptosomes, most of them based on the use of gradients. Neuronal function seems to be critically dependent on the energy provided by mitochondrial respiration. The determination of bioenergetic parameters such as mitochondrial membrane potential, respiratory rates, ATP content and mitochondrial Ca2+ uptake in synaptosomal preparations can provide useful information to analyze the contribution of mitochondrial function to the efficiency of neurotransmission.Synaptic nerve terminals are constantly exposed to extensive Ca2+ fluxes. At the presynaptic terminal, the recovery from calcium oscillations critically depends on the proper mitochondrial function to generate ATP and buffer Ca2+ transients together with an efficient endoplasmic reticulum function.The differential characteristics of synaptic and non-synaptic mitochondria in terms of bioenergetics and free radical production, as well as the response to aging are discussed.Fil: Lores Arnaiz, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Rodriguez, Georgina Emma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Karadayian, Analia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Bustamante, Juanita. Universidad Abierta Interamericana; Argentin