It would be interesting to investigate whether JNK signalling is altered in loss-of-function mouse models where alterations in synaptic activity have been speculated to be a possible root cause of Batten's disease.
Apart from its effects on microtubule binding, phosphorylation can alter tau subcellular localization to dendritic spines (127) or can alter its affinity for the plasma membrane (128), thereby causing alterations in synaptic function (127, 129).
Additionally, iPSC-derived neurons may provide insights into alterations in synaptic plasticity implicated in the pathophysiology of other neurogenetic disorders.
The alterations in synaptic transmission observed in the present study were accompanied by morphological changes of hippocampal synapses.
These abnormalities result in corresponding alterations in synaptic transmission with reduced quantal content.
Next, we aimed to identify the molecular mechanism underlying the observed alterations in synaptic morphology and function in SPL-deficient brains.
Constitutive knockout of glutamate transporters causes major alterations in synaptic glutamate and can produce severe phenotypic alterations potentially confounded by developmental adaptations.
Based on the observed alterations in synaptic morphology of SPLfl/fl/Nesmice, we next assessed the physiological consequences of S1P accumulation on synaptic plasticity in hippocampal CA1 region.
These observations are further supported by qualitative ultrastructural alterations in synaptic architecture in the same subregions of the dentate neuropil.
Despite the absence of neuron loss, we observed alterations in synaptic plasticity, as indicated by elevated paired-pulse facilitation and enhanced long-term potentiation.
There were, however, marked changes in short-term dynamics of evoked EEG responses, which could have been due to alterations in synaptic short-term plasticity, or to reduced inhibitory feedback21.
