Allowing adenosine to mediate state-dependent actions that depend on prior activity in the nervous system. Some of this adenosine arises from prior release of ATP from astrocytes. However there is evidence for direct adenosine release from neurons. In the cerebellum this arises from exocytosis, but in other brain regions, such as hippocampus and cortex, direct activitydependent release of adenosine appears to be mediated via facilitative transporters. The link between neural activity and the production of intracellular adenosine which can be transported into the Anemarsaponin-BIII extracellular space remains unclear. There has been a general idea that the metabolic load of neuronal signalling causes consumption of ATP with consequent production of intracellular adenosine; this would then be extruded from the cell by adenosine clearance mechanisms such as facilitative transporters. Together, these two systems would represent activity-dependent release of adenosine into the extracellular environment. Infusion of adenosine into a single hippocampal pyramidal cell will cause depression of the synaptic inputs to that cell via activation of A1 receptors, suggesting that elevated levels of intracellular adenosine will readily be transported into the extracellular space. On this basis, any process that increases endogenous adenosine levels in neurons should therefore also affect its extracellular concentration. Metabolic processes that consume ATP will cause an increase in intracellular adenosine. As a very large proportion of the brain’s energy budget is consumed by neurons pumping out the Na + that has entered during signalling, the activation of the ATPases is an attractive candidate mechanism to underlie a significant degree of activity-dependent adenosine efflux. The adenosine concentrations observed in this study are slightly higher than the Salvianolic-acid-B reported EC50s of the adenosine A1 receptor of around 1 mM, measured with respect to presynaptic inhibition of neurotransmission, in IP patients we observed no discrepancy between verbal and performance IQ scores. In fact, our participants showed a homogeneous profile. Our sample was not wide, but it showed the same distribution percentage of neurological manifestations reported in the literature. We found that 2 patients out of 10 were affected by mental delays resulting from neurological signs and 1 patient out of 10 was affected by mental delay without any neurological signs. This latter observation is particularly interesting because it suggested that patients with IP might be affected by mental delay also when no neurological damage was present and allowed us to separate mental delay from the neurological framework. The remaining patients with IP manifested no mental retardation, but a detailed cognitive assessment allowed us to detect the presence of learning disabilities. In particular, the learning abilities most affected were arithmetic reasoning and reading skills. In the psychological literature, a comorbidity between dyslexia and dyscalculia is often reported; it is often associated with two largely independent cognitive deficits, namely, a phonological deficit in the case of dyslexia and a deficit in the number module in the case of dyscalculia. In a review study, Jordan reported that reading difficulties aggravated rather than caused mathematical difficulties because compensatory mechanisms associated with reading are less available when dyslexia and dyscalculia co-occur. Furthermore, in our sample reading and arithmetic difficulties cooccurred in 4 patients out of 6. Reading seemed more affected in terms of accuracy than speed and comprehension, whereas all aspects of arithmetic were compromised.