Abstract
Neuroimaging provides for non-invasive evaluation of brain structure and activity and has been employed to suggest possible mechanisms for cognitive aging in humans. However, these imaging procedures have limits in terms of defining cellular and molecular mechanisms. In contrast, investigations of cognitive aging in animal models have mostly utilized techniques that have offered insight on synaptic, cellular, genetic, and epigenetic mechanisms affecting memory. Studies employing magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) in animal models have emerged as an integrative set of techniques bridging localized cellular/molecular phenomenon and broader in vivo neural network alterations. MRI methods are remarkably suited to longitudinal tracking of cognitive function over extended periods permitting examination of the trajectory of structural or activity related changes. Combined with molecular and electrophysiological tools to selectively drive activity within specific brain regions, recent studies have begun to unlock the meaning of fMRI signals in terms of the role of neural plasticity and types of neural activity that generate the signals. The techniques provide a unique opportunity to causally determine how memory-relevant synaptic activity is processed and how memories may be distributed or reconsolidated over time. The present review summarizes research employing animal MRI and MRS in the study of brain function, structure, and biochemistry, with a particular focus on age-related cognitive decline.
Highlights
Among the various techniques in neuroscience, magnetic resonance imaging and spectroscopy are uniquely suited for longitudinal measurements; providing in-depth assessments of neural activity, tissue microstructural organization, and chemistry in the aging brain
In both rats and nonhuman primates BOLD fMRI signals correlate more closely with local field potentials (LFPs) than with multi-unit activity (MUA; Logothetis et al, 2001), recent work in rats indicates that cerebral blood flow (CBF) correlates better with LFPs than do BOLD signals or cerebral blood volume (CBV; Herman et al, 2013)
It is possible that neuromodulatory influences that inhibit the discharge activity of principle cells can increase the BOLD response, while increased discharge activity due to gamma-aminobutyric acid (GABA) antagonist may not alter the BOLD response (Thomsen et al, 2004)
Summary
Among the various techniques in neuroscience, magnetic resonance imaging and spectroscopy are uniquely suited for longitudinal measurements; providing in-depth assessments of neural activity, tissue microstructural organization, and chemistry in the aging brain. Functional and diffusion magnetic resonance imaging (fMRI and dMRI, respectively) are among the most promising MRI modalities that may be used to investigate the relationship between regional changes in neural activity and structural connectivity. These neuroimaging methods have been employed in aging humans to suggest that variability in the decline of several cognitive processes. The medial temporal lobe episodic memory system and a prefrontal cortex and striatal executive function system are highly vulnerable to changes in structure and activity associated with cognitive decline in humans, monkeys, rats, and mice. Known on the synaptic circuitry and mechanisms of learning and memory
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