Modulation of Hippocampal Circuits by Muscarinic and Nicotinic Receptors

Dannenberg, Heinz; Young, Kimberly; Hasselmo, Michael E.

doi:10.3389/fncir.2017.00102

Cited by 81 publications

(70 citation statements)

References 232 publications

(294 reference statements)

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“…Application of nicotinic and muscarinic receptor antagonists atropine (25 µM) and mecamylamine (50 µM) blocked the effects of endogenous acetylcholine release (Figure 1F-H; SC pathway 116 ± 8 %, n = 6 from 3 mice, p > 0.05 ; TA pathway 106 ± 15 %, n = 6 from 3 mice, p > 0.05). Therefore, contrary to our initial hypothesis (Dannenberg et al, 2017; Goswamee and McQuiston, 2019; Hasselmo, 2006; Hasselmo and Schnell, 1994), acetylcholine did not inhibit one pathway more than the other but instead depressed both equally.…”

Section: Resultscontrasting

confidence: 99%

“…A long-standing and influential theory proposes that acetylcholine release in the hippocampus prioritises novel sensory information input to enable incorporation into memory ensembles (Hasselmo, 2006). This theory is based on computational modelling and the observation that SC synaptic inputs are more sensitive than TA inputs to depression caused by exogenous cholinergic agonists (Dannenberg et al, 2017; Hasselmo, 2006; Hasselmo and Schnell, 1994; Hasselmo et al, 1995). In contrast, we show that excitatory synaptic transmission at SC and TA inputs to CA1 are equally depressed by endogenous acetylcholine released in response to optogenetic stimulation (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…Acetylcholine facilitates the induction of synaptic plasticity thereby opening a window for the creation of memory ensembles (Buchanan et al, 2010; Dennis et al, 2016; Hasselmo et al, 1995; Isaac et al, 2009; Mitsushima et al, 2013; Shinoe et al, 2005) and it increases the output gain from primary sensory cortices enhancing signal-to-noise for new sensory information (Eggermann et al, 2014; Fu et al, 2014; Letzkus et al, 2011). It is also proposed to prioritise sensory inputs from the neocortex into memory ensembles within the hippocampus (Dannenberg et al, 2017; Hasselmo, 2006; Hasselmo and Schnell, 1994; Hasselmo et al, 1995) but this critical component of the mechanism by which acetylcholine gates the updating of memory representations has yet to be tested in detail.…”

Section: Introductionmentioning

confidence: 99%

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Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits

Palacios-Filardo

Udakis

Brown

et al. 2020

Preprint

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Acetylcholine release in the hippocampus plays a central role in the formation of new memory representations by facilitating synaptic plasticity. It is also proposed that memory formation requires acetylcholine to enhance responses in CA1 to new sensory information from entorhinal cortex whilst depressing inputs from previously encoded representations in CA3, but this influential theory has not been directly tested. Here, we show that excitatory inputs from entorhinal cortex and CA3 are depressed equally by synaptic release of acetylcholine in CA1. However, greater depression of feedforward inhibition from entorhinal cortex results in an overall enhancement of excitatory-inhibitory balance and CA1 activation. Underpinning the prioritisation of entorhinal inputs, entorhinal and CA3 pathways engage distinct feedforward interneuron subpopulations and depression is mediated differentially by presynaptic muscarinic M3 and M4 receptors respectively. These mechanisms enable acetylcholine to prioritise novel information inputs to CA1 during memory formation and suggest selective muscarinic targets for therapeutic intervention.

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Section: Resultscontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits

Palacios-Filardo

Udakis

Brown

et al. 2020

Preprint

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“…Interestingly, however, NMDARs and group I mGluRs appeared to contribute to different and complementary components of nicotine‐mediated network dynamics. Thus, the activation of both types of glutamate receptors during stimulation with nicotine support nicotine‐mediated network potentiation, which may reflect signal integration and plasticity (Dannenberg, Young, & Hasselmo, ; Sharma & Vijayaraghavan, ; Zarei et al, ). Additionally, studies suggest a direct coupling of α7 nAChRs to G protein signaling cascades that enable a downstream calcium response to persist past the expected time course of channel activation, which may maintain the long‐lasting effects of nicotine.…”

Section: Discussionmentioning

confidence: 99%

Activation of nicotinic acetylcholine receptors induces potentiation and synchronization within in vitro hippocampal networks

Djemil

Chen

Zhang

et al. 2019

Journal of Neurochemistry

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Abbreviations: AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; CaMKII, Ca 2+ /calmodulin-dependent kinase II; CNS, central nervous system; GABA, γ-aminobutyric acid; LTP, long-term potentiation; MEA, microelectrode array; mGluRs, metabotropic glutamate receptors; nAChRs, nicotinic acetylcholine receptors; NMDARs, N-methyl-D-aspartate receptors; RRID, research resource identifier. AbstractNicotinic acetylcholine receptors (nAChRs) are known to play a role in cognitive functions of the hippocampus, such as memory consolidation. Given that they conduct Ca 2+ and are capable of regulating the release of glutamate and γ-aminobutyric acid (GABA) within the hippocampus, thereby shifting the excitatory-inhibitory ratio, we hypothesized that the activation of nAChRs will result in the potentiation of hippocampal networks and alter synchronization. We used nicotine as a tool to investigate the impact of activation of nAChRs on neuronal network dynamics in primary embryonic rat hippocampal cultures prepared from timed-pregnant Sprague-Dawley rats. We perturbed cultured hippocampal networks with increasing concentrations of bath-applied nicotine and performed network extracellular recordings of action potentials using a microelectrode array. We found that nicotine modulated network dynamics in a concentration-dependent manner; it enhanced firing of action potentials as well as facilitated bursting activity. In addition, we used pharmacological agents to determine the contributions of discrete nAChR subtypes to the observed network dynamics. We found that β4-containing nAChRs are necessary for the observed increases in spiking, bursting, and synchrony, while the activation of α7 nAChRs augments nicotine-mediated network potentiation but is not necessary for its manifestation. We also observed that antagonists of N-methyl-D-aspartate receptors (NMDARs) and group I metabotropic glutamate receptors (mGluRs) partially blocked the effects of nicotine. Furthermore, nicotine exposure promoted autophosphorylation of Ca 2+ /calmodulin-dependent kinase II (CaMKII) and serine 831 phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit GluA1. These results suggest that nicotinic receptors induce potentiation and synchronization of hippocampal networks and glutamatergic synaptic transmission. Findings from this work highlight the impact of cholinergic signaling in generating network-wide potentiation in the form of enhanced spiking and bursting | 469 DJEMIL Et aL.

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“…The DG receives a number of neuromodulatory inputs that are able to alter the information processing properties of specific populations of neurons (Prince et al, 2016, Palacios-Filardo andMellor, 2018). Among them, the cholinergic afferents, arriving primarily from the medial forebrain (Mesulam et al, 1983, Wainer et al, 1985, play an important role in modulating cortical circuit activity (Dannenberg et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Cholinergic modulation of dentate gyrus processing through dynamic reconfiguration of inhibitory circuits

Ogando

Pedroncini

Federman

et al. 2019

Preprint

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The dentate gyrus (DG) of the hippocampus plays a key role in memory formation and it is known to be modulated by septal projections. By performing electrophysiology and optogenetics we evaluated the role of cholinergic modulation in the processing of afferent inputs in the DG. We showed that mature granule cells (GCs), but not adult-born immature neurons, have increased responses to afferent perforant path stimuli upon cholinergic modulation. This is due to a highly precise reconfiguration of inhibitory circuits, differentially affecting Parvalbumin and Somatostatin interneurons, resulting in a nicotinic-dependent feedforward perisomatic disinhibition of GCs. This circuit reorganization provides a mechanism by which mature GCs could escape the strong inhibition they receive, creating a window of opportunity for plasticity. Indeed, coincident activation of perforant path inputs with optogenetic release of Ach produced a long-term potentiated response in GCs, which could be crucial for the formation of memories.

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Modulation of Hippocampal Circuits by Muscarinic and Nicotinic Receptors

Cited by 81 publications

References 232 publications

Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits

Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits

Activation of nicotinic acetylcholine receptors induces potentiation and synchronization within in vitro hippocampal networks

Cholinergic modulation of dentate gyrus processing through dynamic reconfiguration of inhibitory circuits

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