N/A, Neurodegeneration leads to Decreased, Neuronal network function in adult brain

Neurodegeneration (retraction of dendrites or axons) or neuronal cell death decreases the number of synaptic connections affecting the neuronal network function (Seeley et al., 2009). Based on neuropathology (Braak and Braak, 1991), neuroimaging (Buckner et al., 2005 and Greicius et al., 2004), and evidence from transgenic animal models (Palop et al., 2007a), it is suggested that neurodegeneration leads to neural network dysfunction (Buckner et al., 2005 and Palop et al., 2006). In human spongiform encephalopathies, which cause rapidly progressive dementia, direct evidence supports disease propagation along affected trans-synaptic connections (Scott et al., 1992). For all other neurodegenerative diseases, there are limited human experimental data supporting the “network degeneration hypothesis.” It is demonstrated as a class-wide phenomenon, with major mechanistic significance, predicting that the spatial patterning of disease relates to some structural, metabolic, or physiological aspect of neural network biology dysfunction. Confirming the network degeneration hypothesis has clinical impact, stimulating development of new network-based diagnostic and disease-monitoring assays.

Is it known how much change in the first event is needed to impact the second? Are there known modulators of the response-response relationships? Are there models or extrapolation approaches that help describe those relationships?

Not enough information exists to understand this linkage quantitativly.

It has been shown at the neuromascular junction of D. melanogaster that quisqualate-type glutamate receptors are blocked by DomA (1 mM) (Lee et al., 2009). However, in crayfish (Procambarus clarkia) the same concentration of DomA has no effect in spike activity (Bierbower and Cooper, 2013).