Cholinergic signaling modulates astrocytic D-serine release
Cholinergic signaling controls brain states, modulates circuit function, and is a
primary therapeutic strategy for a number of diseases including schizophrenia and
Alzheimer's disease. Recent work from our lab has demonstrated in mouse hippocampal
slices that wakefulness-dependent acetylcholine (ACh) release acts on alpha 7 nicotinic
acetylcholine receptors (α7nAChRs) expressed by ... read moreastrocytes to control the
availability of the obligatory NMDA receptor (NMDAR) co-agonist, D-serine. However,
cholinergic dependent changes in hippocampal D-serine levels have not been measured in
vivo. To do this, I established both high pressure liquid chromatography (HPLC) and
microdialysis techniques. Using these two techniques, I found that the level of D-serine
detected correlates with the wakefulness state of the mouse, that the α7nAChRs on
astrocytes are necessary for maintaining normal hippocampal D-serine levels, social
interaction, learning, and memory behaviors in male mice. Ongoing experiments expand our
mechanistic understanding of cholinergic signaling by comparing the astrocyte
α7nAChR conditional knock-out (cKO) mice to neuronal α7nAChR cKO
Thesis (Ph.D.)--Tufts University, 2018.
Submitted to the Dept. of Neuroscience.
Advisor: Phil Haydon.
Committee: Thomas Biederer, and Rob Jackson.
Keyword: Neurosciences.read less