Muscarinic Receptor–Dependent Long-Term Depression in Rat Visual Cortex Is PKC Independent but Requires ERK1/2 Activation and Protein Synthesis

Intact cholinergic innervation of visual cortex is critical for normal processing of visual information and for spatial memory acquisition and retention. However, a complete description of the mechanisms by which the cholinergic system modifies synaptic function in visual cortex is lacking. Previously it was shown that activation of the m1 subtype of muscarinic receptor induces an activity-dependent and partially N-methyl-d-aspartate receptor (NMDAR)-dependent long-term depression (LTD) at layer 4–layer 2/3 synapses in rat visual cortex slices in vitro. The cellular mechanisms downstream of the Gαq coupled m1 receptor required for induction of this LTD (which we term mLTD) are currently unknown. Here, we confirm a role for m1 receptors in mLTD induction and use a series of pharmacological tools to study the signaling molecules downstream of m1 receptor activation in mLTD induction. We found that mLTD is prevented by inhibitors of L-type Ca2+ channels, the Src kinase family, and the mitogen-activated kinase/extracellular kinase. mLTD is also partially dependent on phospholipase C but is unaffected by blocking protein kinase C. mLTD expression can be long-lasting (>2 h) and its long-term maintenance requires translation. Thus we report the signaling mechanisms underlying induction of an m1 receptor-dependent LTD in visual cortex and the requirement of protein synthesis for long-term expression. This plasticity could be a mechanism by which the cholinergic system modifies glutamatergic synapse function to permit normal visual system processing required for cognition.

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Tetanization during GABAA receptor activation induces long-term depression in visual cortex slices

Neuropharmacology ◽

10.1016/0028-3908(93)90178-6 ◽

1993 ◽

Vol 32 (5) ◽

pp. 511-513 ◽

Cited By ~ 7

Author(s):

Nobuo Kato ◽

Hiroshi Yoshimura

Keyword(s):

Visual Cortex ◽

Gabaa Receptor ◽

Receptor Activation ◽

Long Term Depression ◽

Cortex Slices

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Actomyosin-mediated nanostructural remodeling of the presynaptic vesicle pool by cannabinoids induces long-term depression

10.1101/444950 ◽

2018 ◽

Author(s):

Maureen H. McFadden ◽

Hao Xu ◽

Yihui Cui ◽

Rebecca A. Piskorowski ◽

Christophe Leterrier ◽

...

Keyword(s):

Molecular Mechanisms ◽

Receptor Activation ◽

Synaptic Function ◽

Actin Binding ◽

Functional Plasticity ◽

Structural Reorganization ◽

Long Term Depression ◽

Dynamic Regulation ◽

Presynaptic Vesicle

AbstractEndo- and exocannabinoids, such as the psychoactive component of marijuana, exert their effects on brain function by inducing several forms of synaptic plasticity through the modulation of presynaptic vesicle release1-3. However, the molecular mechanisms underlying the widely expressed endocannabinoid-mediated long-term depression3 (eCB-LTD), are poorly understood. Here, we reveal that eCB-LTD depends on the contractile properties of the pre-synaptic actomyosin cytoskeleton. Preventing this contractility, both directly by inhibiting non-muscle myosin II NMII ATPase and indirectly by inhibiting the upstream Rho-associated kinase ROCK, abolished long-term, but not short-term forms of cannabinoid-induced functional plasticity in both inhibitory hippocampal and excitatory cortico-striatal synapses. Furthermore, using 3D superresolution microscopy, we find an actomyosin contractility-dependent redistribution of synaptic vesicle pools within the presynaptic compartment following cannabinoid receptor activation, leading to vesicle clustering and depletion from the pre-synaptic active zone. These results suggest that cannabinoid-induced functional plasticity is mediated by a nanoscale structural reorganization of the presynaptic compartment produced by actomyosin contraction. By introducing the contractile NMII as an important actin binding/structuring protein in the dynamic regulation of synaptic function, our results open new perspectives in the understanding of mechanisms of synaptic and cognitive function, marijuana intoxication and psychiatric pathogenesis.

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Layer 2/3 Synapses in Monocular and Binocular Regions of Tree Shrew Visual Cortex Express mAChR-Dependent Long-Term Depression and Long-Term Potentiation

Journal of Neurophysiology ◽

10.1152/jn.01134.2007 ◽

2008 ◽

Vol 100 (1) ◽

pp. 336-345 ◽

Cited By ~ 20

Author(s):

Portia McCoy ◽

Thomas T. Norton ◽

Lori L. McMahon

Keyword(s):

Visual Cortex ◽

Learning And Memory ◽

Tree Shrew ◽

Long Term Potentiation ◽

Synaptic Function ◽

Muscarinic Acetylcholine Receptors ◽

Long Term Depression ◽

Term Potentiation ◽

Layer 2

Acetylcholine is an important modulator of synaptic efficacy and is required for learning and memory tasks involving the visual cortex. In rodent visual cortex, activation of muscarinic acetylcholine receptors (mAChRs) induces a persistent long-term depression (LTD) of transmission at synapses recorded in layer 2/3 of acute slices. Although the rodent studies expand our knowledge of how the cholinergic system modulates synaptic function underlying learning and memory, they are not easily extrapolated to more complex visual systems. Here we used tree shrews for their similarities to primates, including a visual cortex with separate, defined regions of monocular and binocular innervation, to determine whether mAChR activation induces long-term plasticity. We find that the cholinergic agonist carbachol (CCh) not only induces long-term plasticity, but the direction of the plasticity depends on the subregion. In the monocular region, CCh application induces LTD of the postsynaptic potential recorded in layer 2/3 that requires activation of m3 mAChRs and a signaling cascade that includes activation of extracellular signal-regulated kinase (ERK) 1/2. In contrast, layer 2/3 postsynaptic potentials recorded in the binocular region express long-term potentiation (LTP) following CCh application that requires activation of m1 mAChRs and phospholipase C. Our results show that activation of mAChRs induces long-term plasticity at excitatory synapses in tree shrew visual cortex. However, depending on the ocular inputs to that region, variation exists as to the direction of plasticity, as well as to the specific mAChR and signaling mechanisms that are required.

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Hippocampal long term memory: Effect of the cholinergic system on local protein synthesis

Neurobiology of Learning and Memory ◽

10.1016/j.nlm.2013.09.013 ◽

2013 ◽

Vol 106 ◽

pp. 246-257 ◽

Cited By ~ 19

Author(s):

Daniele Lana ◽

Francesca Cerbai ◽

Jacopo Di Russo ◽

Francesca Boscaro ◽

Ambra Giannetti ◽

...

Keyword(s):

Protein Synthesis ◽

Memory Effect ◽

Cholinergic System ◽

Long Term Memory ◽

Term Memory ◽

Local Protein Synthesis ◽

Local Protein

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Involvement of Synaptic NR2B-Containing NMDA Receptors in Long-Term Depression Induction in the Young Rat Visual Cortex In Vitro

The Chinese Journal of Physiology ◽

10.4077/cjp.2011.amm020 ◽

2011 ◽

Vol 54 (3) ◽

pp. 190-195 ◽

Cited By ~ 3

Author(s):

Yan-Hai Li

Keyword(s):

Visual Cortex ◽

Nmda Receptors ◽

Long Term Depression ◽

Young Rat

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Impairment of cerebellar long-term depression and GABAergic transmission in prion protein deficient mice ectopically expressing PrPLP/Dpl

Scientific Reports ◽

10.1038/s41598-020-72753-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Yasushi Kishimoto ◽

Moritoshi Hirono ◽

Ryuichiro Atarashi ◽

Suehiro Sakaguchi ◽

Tohru Yoshioka ◽

...

Keyword(s):

Synaptic Transmission ◽

Prion Protein ◽

Neural Plasticity ◽

Late Onset ◽

Eyeblink Conditioning ◽

Electrophysiological Study ◽

Synaptic Function ◽

Long Term Depression ◽

Underlying Mechanisms

Abstract Prion protein (PrPC) knockout mice, named as the “Ngsk” strain (Ngsk Prnp0/0 mice), show late-onset cerebellar Purkinje cell (PC) degeneration because of ectopic overexpression of PrPC-like protein (PrPLP/Dpl). Our previous study indicated that the mutant mice also exhibited alterations in cerebellum-dependent delay eyeblink conditioning, even at a young age (16 weeks of age) when neurological changes had not occurred. Thus, this electrophysiological study was designed to examine the synaptic function of the cerebellar cortex in juvenile Ngsk Prnp0/0 mice. We showed that Ngsk Prnp0/0 mice exhibited normal paired-pulse facilitation but impaired long-term depression of excitatory synaptic transmission at synapses between parallel fibres and PCs. GABAA-mediated inhibitory postsynaptic currents recorded from PCs were also weakened in Ngsk Prnp0/0 mice. Furthermore, we confirmed that Ngsk Prnp0/0 mice (7–8-week-old) exhibited abnormalities in delay eyeblink conditioning. Our findings suggest that these alterations in both excitatory and inhibitory synaptic transmission to PCs caused deficits in delay eyeblink conditioning of Ngsk Prnp0/0 mice. Therefore, the Ngsk Prnp0/0 mouse model can contribute to study underlying mechanisms for impairments of synaptic transmission and neural plasticity, and cognitive deficits in the central nervous system.

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Muscarinic Receptor-Dependent Long Term Depression in the Perirhinal Cortex and Recognition Memory are Impaired in the rTg4510 Mouse Model of Tauopathy

Neurochemical Research ◽

10.1007/s11064-018-2487-x ◽

2018 ◽

Vol 44 (3) ◽

pp. 617-626 ◽

Cited By ~ 1

Author(s):

Sarah E. Scullion ◽

Gareth R. I. Barker ◽

E. Clea Warburton ◽

Andrew D. Randall ◽

Jonathan T. Brown

Keyword(s):

Recognition Memory ◽

Mouse Model ◽

Muscarinic Receptor ◽

Perirhinal Cortex ◽

Long Term Depression ◽

Rtg4510 Mouse

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Modulation of Presynaptic Calcium Transients by Metabotropic Glutamate Receptor Activation: A Differential Role in Acute Depression of Synaptic Transmission and Long-Term Depression

Journal of Neuroscience ◽

10.1523/jneurosci.22-16-06885.2002 ◽

2002 ◽

Vol 22 (16) ◽

pp. 6885-6890 ◽

Cited By ~ 65

Author(s):

Guido C. Faas ◽

Hita Adwanikar ◽

Robert W. Gereau ◽

Peter Saggau

Keyword(s):

Synaptic Transmission ◽

Glutamate Receptor ◽

Metabotropic Glutamate Receptor ◽

Receptor Activation ◽

Calcium Transients ◽

Long Term Depression ◽

Metabotropic Glutamate ◽

Presynaptic Calcium

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Calcium: A Trigger for Long-Term Depression and Potentiation in the Hippocampus

Physiology ◽

10.1152/physiologyonline.1994.9.6.256 ◽

1994 ◽

Vol 9 (6) ◽

pp. 256-260

Author(s):

D Debanne ◽

SM Thompson

Keyword(s):

Protein Kinases ◽

Long Term Potentiation ◽

Receptor Activation ◽

Synaptic Strength ◽

Excitatory Synapses ◽

Long Term Depression ◽

Aspartate Receptor ◽

Term Potentiation ◽

Different Levels

Two opposing types of plasticity at excitatory synapses in the hippocampus, long-term potentiation and depression, require N-methyl-D-aspartate receptor activation and Ca2+ influx for their induction.The direction of the change in synaptic strength is determined by a balance between phosphorylation and dephosphorylation, as regulated by protein kinases and phosphatases that are activated selectively by different levels of intracellular Ca2+.

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