Cholinergic Deafferentation of Dorsal Hippocampus by Fimbria‐Fornix Lesioning Differentially Regulates Subtypes (m1‐m5) of Muscarinic Receptors

Wall, Stephen; Wolfe, Barry B.; Kromer, Lawrence F.

doi:10.1046/j.1471-4159.1994.62041345.x

Cited by 34 publications

(8 citation statements)

References 42 publications

(47 reference statements)

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“…Several studies have reported changes of muscarinic receptor expression after manipulations that affect cholinergic transmission (Wall et al, 1992(Wall et al, , 1994Inoue et al, 1995;Gunasena et al, 1995;Levey et al, 1995;Harrison et al, 1996;Rouss and Levey, 1997;Erb et al, 2001;Volpicelli-Daley et al, 2003). Although these studies suggest that muscarinic receptor expression levels may be regulated according to the availability of acetylcholine to maintain a homeostatic balance, our results so far suggest increased muscarinic receptor expression without decreased acetylcholine synthetic capacity (Jin et al, 2005).…”

Section: Functional Implications Of Plasticity Of Muscarinic Acetylchcontrasting

confidence: 48%

Effects of cochlear ablation on muscarinic acetylcholine receptor binding in the rat cochlear nucleus

Jin

Godfrey

2006

J. Neurosci. Res.

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Cholinergic synapses in the cochlear nucleus (CN) have been reported to modulate spontaneous activity via muscarinic acetylcholine receptors. In this study, muscarinic receptor binding was measured as specific binding of 1-[N-methyl-(3)H]scopolamine in CN regions of control rats and 7 days, 1 month, and 2 months after unilateral cochlear ablation. In control rats, the strongest binding was found in granular regions, followed in order by fusiform soma, molecular, and deep layers of the dorsal cochlear nucleus (DCN), with much lower binding in the anteroventral CN (AVCN) and posteroventral CN (PVCN). After unilateral cochlear ablation, binding in the AVCN, PVCN, and their associated granular regions on the lesion side became progressively greater than on the control side through 2 months after lesion. A significant asymmetry, with binding higher on the lesion side, was also found in the DCN fusiform soma layer at 7 days, and there and in the DCN deep layer at 1 and 2 months after lesion. There was also evidence of increased binding on the control side in most CN regions. By contrast, binding in the ipsilateral facial nucleus decreased, compared with the control side, by 7 days after the lesion and showed some recovery toward symmetry by 2 months after lesion, and there was no evidence for contralateral changes. These muscarinic receptor binding changes reflect receptor plasticity after loss of auditory nerve innervation. Such plasticity may underlie some of the central auditory functional changes that occur following peripheral lesions, such as tinnitus and hyperacusis.

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Section: Functional Implications Of Plasticity Of Muscarinic Acetylchcontrasting

confidence: 48%

Effects of cochlear ablation on muscarinic acetylcholine receptor binding in the rat cochlear nucleus

Jin

Godfrey

2006

J. Neurosci. Res.

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“…The more intense and persistent IED frequency potentiation in the PTZ‐septal slices (Fig. 2A,C) might be explained by the more effective coupling of muscarinic receptors with G proteins following an early seizure (Potier et al., 2005) combined with the increased availability of endogenous ACh in the septal hippocampus (because of the stronger fimbria‐fornix cholinergic‐muscarinic input there (Wyss et al., 1980; Nicoll, 1985; Joyce et al., 1989; Wall et al., 2008)).…”

Section: Discussionmentioning

confidence: 99%

“…Extracellular ACh increase (by eserine) had the most profound effect on IED frequency in PTZ‐septal slices. The septal hippocampal‐parahippocampal connectivity (Dolorfo & Amaral, 1998; Delatour & Witter, 2002; Kerr et al., 2007), with its relatively stronger fimbria‐fornix muscarinic input (Wyss et al., 1980; Nicoll, 1985; Joyce et al., 1989; Wall et al., 2008) suggests that a local transient ACh overflow in a conditioned subject (i.e., a subject with a history of early life sustained generalized seizures) would increase IED output to the entorhinal cortex, which might then be further amplified within the hippocampal‐entorhinal cortex loop (Chrobak & Buzsaki, 1994; Chrobak et al., 2000). This in turn might contribute to a transient disruption of memory function (Zhou et al., 2007; Kleen et al., 2010) as indeed has been suggested for interictal spiking (Binnie, 2003; Pressler et al., 2005).…”

Section: Discussionmentioning

confidence: 99%

Endogenous ACh effects on NMDA‐induced interictal‐like discharges along the septotemporal hippocampal axis of adult rats and their modulation by an early life generalized seizure

Mikroulis

Psarropoulou

2012

Epilepsia

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SUMMARYPurpose: Our earlier findings of the modulation of cholinergic neurotransmission by an early life generalized seizure and the reported interaction between muscarinic and N-methyl-D-aspartate (NMDA) receptors prompted us to investigate the effects of endogenous acetylcholine (ACh) on the frequency (Hz) of the epileptiform discharges following NMDA-receptor activation in the hippocampal slice. Methods: A sustained (>20 min) generalized convulsion was induced in Sprague-Dawley juvenile rats by intraperitoneal injection with pentylenetetrazole (PTZ, 70-90 mg/ kg) at postnatal day (P) 20. Temporal and septal hippocampal slices were prepared of normal (N) and PTZ-treated (PTZ) adult ( ‡P60) rats, and CA3 field potentials were recorded during perfusion with Mg 2+ -free artificial cerebrospinal fluid (ACSF) or with ACSF containing 50 lM 4-aminopyridine (4-AP). Key Findings: In Mg 2+ -free ACSF, spontaneous interictallike epileptiform discharges (IEDs) were recorded in all slices, with significantly higher frequencies in temporal (0.46 ± 0.03 Hz, n = 85) versus septal slices (0.20 ± 0.02 Hz, n = 47, p < 0.000001) but no consistent differences in any other group (i.e., male vs. female or N vs. PTZ). The anticholinesterase eserine (10 lM) increased their frequencies by 150-200% in N-septal and in all temporal slices and by 300% in PTZ-septal slices (p = 0.0028). In 60% of the slices the excitatory effect persisted throughout drug perfusion, whereas in the remaining ones it was distinguished in two phases: an early ''transient'' and a late ''steady state.'' The steady-state frequencies resembled the predrug ones in N slices but remained significantly elevated in PTZ slices, especially in the septal group. The muscarinic antagonist atropine (1 lM) decreased IED frequency in all slices (n = 36, p = 0.005) and also fully reversed the eserine effect (n = 38, p < 0.0001). In 4-AP ACSF, eserine increased spontaneous IED frequency (n = 21) in N and PTZ slices alike; IEDs were subsequently abolished by addition of the NMDA-receptor antagonist D())-2-amino-5-phosphonopentanoic acid (AP5; 50 lM, n = 6).Significance: These results demonstrate an intrinsic tonic positive muscarinic acetylcholine receptor (mAChR) contribution to the frequency of NMDA receptor-dependent epileptiform discharges that is amplified following an elevation of endogenous ACh and is more pronounced in the septal hippocampus. Moreover, this positive mAChR contribution to the frequency of IEDs is even more pronounced and persistent in the septal extremity after an early life generalized sustained convulsion. This cholinergic enhancement of the excitatory septal hippocampal output may influence cognitive function and performance, and possibly the adult seizure threshold.

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“…Pirenzepine has been shown to stimulate ACh release (34), although the mechanism is unclear. The m2 receptors are located on presynaptic cholinergic terminals projecting to the hippocampus (35). Activation of this muscarinic subtype inhibits the release of ACh, whereas blockade of this subtype leads to increased levels of ACh (2,36,37).…”

Section: Discussionmentioning

confidence: 99%

“…The m1, m3, and m5 receptors can couple to the G q family, G q and G 11 (38), and are expressed in pyramidal cells (39). However, muscarinic receptor-stimulated G q/11 -specific 35 SGTPγ (GTP labeled on the gamma phosphate with 35 S) binding to G proteins, which has been used as a sensitive assay of G protein-coupled receptor activation, was virtually abolished in the hippocampus of m1 receptor KO mice (38). This suggests a role for the m1 receptor subtype as the primary G q/ 11 -coupled muscarinic receptor in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Nicotinic and muscarinic agonists and acetylcholinesterase inhibitors stimulate a common pathway to enhance GluN2B-NMDAR responses

Ishibashi

Yamazaki

Miledi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Nicotinic and muscarinic ACh receptor agonists and acetylcholinesterase inhibitors (AChEIs) can enhance cognitive function. However, it is unknown whether a common signaling pathway is involved in the effect. Here, we show that in vivo administration of nicotine, AChEIs, and an m1 muscarinic (m1) agonist increase glutamate receptor, ionotropic, N-methyl D-aspartate 2B (GluN2B)-containing NMDA receptor (NR2B-NMDAR) responses, a necessary component in memory formation, in hippocampal CA1 pyramidal cells, and that coadministration of the m1 antagonist pirenzepine prevents the effect of cholinergic drugs. These observations suggest that the effect of nicotine is secondary to increased release of ACh via the activation of nicotinic ACh receptors (nAChRs) and involves m1 receptor activation through ACh. In vitro activation of m1 receptors causes the selective enhancement of NR2B-NMDAR responses in CA1 pyramidal cells, and in vivo exposure to cholinergic drugs occludes the in vitro effect. Furthermore, in vivo exposure to cholinergic drugs suppresses the potentiating effect of Src on NMDAR responses in vitro. These results suggest that exposure to cholinergic drugs maximally stimulates the m1/guanine nucleotide-binding protein subunit alpha q/PKC/proline-rich tyrosine kinase 2/Src signaling pathway for the potentiation of NMDAR responses in vivo, occluding the in vitro effects of m1 activation and Src. Thus, our results indicate not only that nAChRs, ACh, and m1 receptors are on the same pathway involving Src signaling but also that NR2B-NMDARs are a point of convergence of cholinergic and glutamatergic pathways involved in learning and memory. m1 muscarinic receptor | donepezil | hippocampus N icotinic and muscarinic agonists can produce cognitive enhancement (1, 2). Acetylcholinesterase inhibitors (AChEIs) also cause cognitive enhancement by increasing ACh levels (3, 4). However, it is largely unknown whether the effect of ACh is mediated by nicotinic ACh receptors (nAChRs), muscarinic receptors, or both. Studies involving cholinergic lesions and local administration of cholinergic antagonists indicate that both nAChRs and muscarinic receptors located in the hippocampus are of particular importance for learning and memory processes (5-8). However, the mechanisms by which these receptors mediate cognitive enhancement largely remain to be elucidated.Synaptic plasticity is thought to be a critical component underlying learning and memory (9, 10), and the NMDA receptor (NMDAR) is a key component of synaptic plasticity (9, 11). Thus, studies of the modulation of NMDAR responses and longterm potentiation (LTP) induction by cholinergic drugs (12)(13)(14)(15)(16)(17)(18)(19)(20) help elucidate the mechanisms of cholinergic facilitation of learning and memory. In vitro acute nicotine can potentiate NMDAR-mediated responses in CA1 pyramidal cells in hippocampal slices via at least two different mechanisms (16,18). One of these mechanisms is absent after a selective cholinergic lesion (21) and is paradoxically blocked by the mu...

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Cholinergic Deafferentation of Dorsal Hippocampus by Fimbria‐Fornix Lesioning Differentially Regulates Subtypes (m1‐m5) of Muscarinic Receptors

Cited by 34 publications

References 42 publications

Effects of cochlear ablation on muscarinic acetylcholine receptor binding in the rat cochlear nucleus

Effects of cochlear ablation on muscarinic acetylcholine receptor binding in the rat cochlear nucleus

Endogenous ACh effects on NMDA‐induced interictal‐like discharges along the septotemporal hippocampal axis of adult rats and their modulation by an early life generalized seizure

Nicotinic and muscarinic agonists and acetylcholinesterase inhibitors stimulate a common pathway to enhance GluN2B-NMDAR responses

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