Neurophysiological alterations in the nucleus reuniens of a mouse model of Alzheimer's disease

• Published in: Neurobiology of aging Vol. 88; pp. 1 - 10
• Main Authors: Walsh, Darren A., Brown, Jon T., Randall, Andrew D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2020
• Subjects: Action Potentials; Alzheimer Disease - etiology; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloidopathy; Animals; Calcium Channels - metabolism; Cerebral Cortex - physiopathology; Disease Models, Animal; Hippocampus - physiopathology; Hyperexcitability; J20; Male; Membrane Potentials; Mice, Inbred C57BL; Mice, Transgenic; Midline Thalamic Nuclei - physiopathology; Midline thalamus; Nucleus reuniens; Patch-Clamp Techniques; Thalamus - physiopathology; J20; Midline thalamus; Nucleus reuniens; Amyloidopathy; Alzheimer's disease; Hyperexcitability
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2019.12.006

Recently, increased neuronal activity in nucleus reuniens (Re) has been linked to hyperexcitability within hippocampal-thalamo-cortical networks in the J20 mouse model of amyloidopathy. Here in vitro whole-cell patch clamp recordings were used to compare old pathology-bearing J20 mice and wild-type controls to examine whether altered intrinsic electrophysiological properties could contribute to the amyloidopathy-associated Re hyperactivity. A greater proportion of Re neurons display hyperpolarized membrane potentials in J20 mice without changes to the incidence or frequency of spontaneous action potentials. Re neurons recorded from J20 mice did not exhibit increased action potential generation in response to depolarizing current stimuli but an increased propensity to rebound burst following hyperpolarizing current stimuli. Increased rebound firing did not appear to result from alterations to T-type Ca2+ channels. Finally, in J20 mice, there was an ~8% reduction in spike width, similar to what has been reported in CA1 pyramidal neurons from multiple amyloidopathy mice. We conclude that alterations to the intrinsic properties of Re neurons may contribute to hippocampal-thalmo-cortical hyperexcitability observed under pathological beta-amyloid load.
•Re neurons display hyperpolarized resting membrane potentials in J20 mice.•Re neurons exhibit increased rebound bursting to hyperpolarizing stimuli.•This increased rebound firing was not a result of altered T-type Ca2+ conductances.•Finally we observed a decrease in action potential width.