This will enable predictions of the decay of the magnetization due to dephasing of the spins induced by changes in blood oxygenation; this is the BOLD effect. We might have the tools to manipulate synaptic connectivity and neurotransmitters such as dopamine or serotonin (e.g., by inactivation of the postsynaptic receptors).
We will advance the imaging technology to allow simultaneous measurements from a number of locations at a time in awake behaving animals and combine the fine- and coarse-grain tools (again, both experimentally and in a computational framework) to fill in the gaps. Then, we can begin to address questions of distributed computation (i.e., those arising from the interplay of multiple cortical areas) and the importance of the “modulatory” neurotransmission systems. We will have the tools Small Molecule Compound Library to probe the factors that empower conscious behaviors such as successful retrieval of a memory trace or making a correct decision. Inclusion of nonneuronal measures (e.g., metabolic activity, chemical excitability, and structural plasticity of glia) will put the questions of plasticity and development
within reach. DAPT A natural deliverable from these efforts will be a set of tools for preclinical studies in model organisms. This is because interpretation of noninvasive functional imaging and understanding of the mechanisms of brain disease require investigation of the same types of neuroglial, neurovascular, and neurometabolic interactions. Collectively, these new tools will enable translation of the detailed and elegant mechanistic approaches to intact brains; today this is possible only in cell cultures and isolated neuronal tissues. In neurodegeneration, these tools will allow us to ask a range of critical questions, such as: does the breakdown in energy metabolism precede dysregulation of neuronal electrical activity? Does the initial pathology, manifested as altered ionic homeostasis or reduced production of ATP, originate in neurons or astrocytes? Bay 11-7085 Are certain types of neurons more vulnerable than others? In mental disease, such tools will make
it possible to modulate the excitability of the dendritic trees and to track the resulting alterations in the release of neurotransmitters and synaptic connectivity. One also could ask whether the common denominator among the models exhibiting abnormal sensorimotor gating might converge upon the same endpoint functional network organization. In the study of headaches, these tools can clarify the chain of events underlying the spontaneous initiation and propagation of cortical spreading depression. For instance, we can ask whether or not the stress accompanying cortical spreading depression can be explained by a metabolic failure where oxygen demand exceeds the supply, resulting in a shortage of the ATP required for the effective neuronal repolarization.