Monitoring Neurotransmitter Amino Acids by Microdialysis: Pharmacodynamic Applications

Parrot, Sandrine; Renaud, Bernard; Zimmer, Luc; Denoroy, Luc

doi:10.1002/9781118011294.ch5

Cited by 1 publication

(1 citation statement)

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“…Despite the unchanged global glutamate levels found in the DMSXL hippocampus by microdialysis, it is conceivable that the spatial resolution of this sampling technique is not sufficient to target specific subregions of the hippocampus (DG vs. CA1). In addition, individual synaptic compartments or membrane microdomains in this complex and heterogeneous brain region cannot be sampled by this approach [ 34 ]. To overcome this limitation, we used ex vivo patch clamp techniques on hippocampal slices to specifically investigate events on the membrane of CA1 and DG neurons.…”

Section: Discussionmentioning

confidence: 99%

DM1 Transgenic Mice Exhibit Abnormal Neurotransmitter Homeostasis and Synaptic Plasticity in Association with RNA Foci and Mis-Splicing in the Hippocampus

Potier

Lallemant

Parrot

et al. 2022

IJMS

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Myotonic dystrophy type 1 (DM1) is a severe neuromuscular disease mediated by a toxic gain of function of mutant RNAs. The neuropsychological manifestations affect multiple domains of cognition and behavior, but their etiology remains elusive. Transgenic DMSXL mice carry the DM1 mutation, show behavioral abnormalities, and express low levels of GLT1, a critical regulator of glutamate concentration in the synaptic cleft. However, the impact of glutamate homeostasis on neurotransmission in DM1 remains unknown. We confirmed reduced glutamate uptake in the DMSXL hippocampus. Patch clamp recordings in hippocampal slices revealed increased amplitude of tonic glutamate currents in DMSXL CA1 pyramidal neurons and DG granule cells, likely mediated by higher levels of ambient glutamate. Unexpectedly, extracellular GABA levels and tonic current were also elevated in DMSXL mice. Finally, we found evidence of synaptic dysfunction in DMSXL mice, suggestive of abnormal short-term plasticity, illustrated by an altered LTP time course in DG and in CA1. Synaptic dysfunction was accompanied by RNA foci accumulation in localized areas of the hippocampus and by the mis-splicing of candidate genes with relevant functions in neurotransmission. Molecular and functional changes triggered by toxic RNA may induce synaptic abnormalities in restricted brain areas that favor neuronal dysfunction.

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Section: Discussionmentioning

confidence: 99%