M1 muscarinic receptor signaling in mouse hippocampus and cortex

Porter, Amy C.; Bymaster, Frank P.; DeLapp, Neil W.; Yamada, Masahisa; Wess, Jürgen; Hamilton, Susan; Nathanson, Neil M.; Felder, Christian C.

doi:10.1016/s0006-8993(02)02721-x

Cited by 84 publications

(68 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Likewise, there is evidence for extensive expression of mACh receptors, particularly of the M 1 subtype, in both neuronal soma and dendrites in rat (Levey et al, 1995) and human (Shiozaki et al, 2001) hippocampal pyramidal cells. The M 1 mACh receptor subtype preferentially couples via G␣ q/11 -proteins to activation of phospholipase C, and recent studies have revealed that agonist-stimulated G␣ q/11 -[ 35 S]GTP␥S binding is abolished in hippocampal membranes from M 1 mACh receptor knock-out mice (Porter et al, 2002). Furthermore, activation of mACh receptors on CA1 pyramidal neurons leads to IP 3 -dependent Ca 2ϩ waves that propagate from the dendrites to the soma, in which they invade the nucleus (Power and Sah, 2002).…”

Section: Discussionmentioning

confidence: 99%

Imaging of Muscarinic Acetylcholine Receptor Signaling in Hippocampal Neurons: Evidence for Phosphorylation-Dependent and -Independent Regulation by G-Protein-Coupled Receptor Kinases

Willets¹,

Nash²,

Challiss³

et al. 2004

J. Neurosci.

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Imaging of Muscarinic Acetylcholine Receptor Signaling in Hippocampal Neurons: Evidence for Phosphorylation-Dependent and -Independent Regulation by G-Protein-Coupled Receptor Kinases

Willets¹,

Nash²,

Challiss³

et al. 2004

J. Neurosci.

View full text Add to dashboard Cite

“…Thus, we hypothesize that, although the density of the newly sprouted cholinergic fibers in hippocampus is quite low, they must provide enough cholinergic activity to reestablish M 1 receptor-Gq coupling and rescue mLTD. This seems plausible because maximal stimulation of PI hydrolysis occurs by stimulating only 15% of the total number of M 1 receptors expressed in hippocampus (Porter et al, 2002). The tight temporal relationship between the rescue of mLTD expression and the reappearance of VAChTpositive boutons throughout hippocampus lends strong support to the idea that the cholinergic reinnervation is causal to mLTD rescue.…”

Section: Altered M 1 Signaling After Cholinergic Denervation and Ingrmentioning

confidence: 94%

Sympathetic Sprouting Drives Hippocampal Cholinergic Reinnervation That Prevents Loss of a Muscarinic Receptor-Dependent Long-Term Depression at CA3–CA1 Synapses

Scheiderer

McCutchen²,

Thacker³

et al. 2006

J. Neurosci.

View full text Add to dashboard Cite

Degeneration of septohippocampal cholinergic neurons results in memory deficits attributable to loss of cholinergic modulation of hippocampal synaptic circuits. A remarkable consequence of cholinergic degeneration is the sprouting of noradrenergic sympathetic fibers from the superior cervical ganglia into hippocampus. The functional impact of sympathetic ingrowth on synaptic physiology has never been investigated. Here, we report that, at CA3-CA1 synapses, a Hebbian form of long-term depression (LTD) induced by muscarinic M 1 receptor activation (mLTD) is lost after medial septal lesion. Unexpectedly, expression of mLTD is rescued by sympathetic sprouting. These effects are specific because LTP and other forms of LTD are unaffected. The rescue of mLTD expression is coupled temporally with the reappearance of cholinergic fibers in hippocampus, as assessed by the immunostaining of fibers for VAChT (vesicular acetylcholine transporter). Both the cholinergic reinnervation and mLTD rescue are prevented by bilateral superior cervical ganglionectomy, which also prevents the noradrenergic sympathetic sprouting. The new cholinergic fibers likely originate from the superior cervical ganglia because unilateral ganglionectomy, performed when cholinergic reinnervation is well established, removes the reinnervation on the ipsilateral side. Thus, the temporal coupling of the cholinergic reinnervation with mLTD rescue, together with the absence of reinnervation and mLTD expression after ganglionectomy, demonstrate that the autonomic-driven cholinergic reinnervation is essential for maintaining mLTD after central cholinergic cell death. We have discovered a novel phenomenon whereby the autonomic and central nervous systems experience structural rearrangement to replace lost cholinergic innervation in hippocampus, with the consequence of preserving a form of LTD that would otherwise be lost as a result of cholinergic degeneration.

show abstract

“…These alterations of m 1 -and m 3 -MAChR expression correlate with cholinergic hypofunction in short-term and prolonged STZ-induced DM. It should be noted that m 1 -and m 3 -MAChRs are abundantly expressed in the brain regions involved in cognition, including the cerebral cortex, hippocampus and striatum (Porter et al, 2002). As a rule, most animal models of obesity and hyperinsulinemia are associated with increased vagal cholinergic activity that is strongly associated with the m 3 -MAChR expressed in the brain and the peripheral tissues (Gautam et al, 2008).…”

Section: Acetylcholine Signalingmentioning

confidence: 99%