Aging in Sensory and Motor Neurons Results in Learning Failure in Aplysia californica

Kempsell, Andrew T.; Fieber, Lynne A.

doi:10.1371/journal.pone.0127056

Cited by 24 publications

(35 citation statements)

References 70 publications

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“…As it has been previously shown that L-Glu activates NMDA-like receptors in Aplysia SN (Carlson and Fieber, 2011 ), it is possible that the decrements in iGluR signaling described in this study are due to NMDAR dysfunction similar to that seen in mammalian models of aging (Foster et al, 2001 ). Altered iGluR composition in aged Aplysia neurons likely contributes to the changes in learning and related changes in proxies for synaptic plasticity found in this study and others (Kempsell and Fieber, 2015 ).…”

Section: Discussionsupporting

confidence: 71%

“…PMA and dbcAMP previously were shown to increase tail SN excitability and facilitate tail SN-MN transmission (Byrne et al, 1988 ; Kandel, 2001 ). We recently reported that synaptic facilitation declined during aging in the TWR circuit whether the sensitizing stimulus was electrical stimulation or 5-HT treatment (Kempsell and Fieber, 2015 ). The ability of isolated aged II SN to respond to PMA and dbcAMP with facilitiated L-Glu-induced currents implied that excitability modulating intracellular pathways were at least partially intact in aging, and prompted questions about whether these agents could restore TWR responses to sensitizing stimuli that were absent in aged animals.…”

Section: Resultsmentioning

confidence: 99%

“…These elemental processes define the role of 5-HT in stimulating the formation and maintenance of memory. We have recently described changes in short-term memory for sensitization in TWR and related declines in facilitation between tail SN-MN synapses during aging, suggesting that nonassociative learning is impaired in aged Aplysia (Kempsell and Fieber, 2015 ). In that study, 5-HT-exposed, mature SN in intact ganglia responded to depolarizing stimuli with multiple AP compared to the single AP response before 5-HT, whereas aged SN showed no change in excitability with 5-HT.…”

Section: Discussionmentioning

confidence: 99%

“…Animals were anesthetized by injection of isotonic MgCl 2 (~50% animal weight by volume) into the body cavity. A ganglia-tail preparation was made, consisting of either the left or right pleural-pedal hemiganglia that remained connected to the tail by nerve p9 (Kempsell and Fieber, 2015 ); all other connectives were severed. The ganglia-tail preparation was pinned tightly to a Sylgarded dish.…”

Section: Methodsmentioning

confidence: 99%

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Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica

Kempsell

Fieber

2015

Front. Aging Neurosci.

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Brain aging is associated with declines in synaptic function that contribute to memory loss, including reduced postsynaptic response to neurotransmitters and decreased neuronal excitability. To understand how aging affects memory in a simple neural circuit, we studied neuronal proxies of memory for sensitization in mature vs. advanced age Aplysia californica (Aplysia). L-Glutamate-(L-Glu-) evoked excitatory currents were facilitated by the neuromodulator serotonin (5-HT) in sensory neurons (SN) isolated from mature but not aged animals. Activation of protein kinase A (PKA) and protein kinase C (PKC) signaling rescued facilitation of L-Glu currents in aged SN. Similarly, PKA and PKC activators restored increased excitability in aged tail SN. These results suggest that altered synaptic plasticity during aging involves defects in second messenger systems.

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Section: Discussionsupporting

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica

Kempsell

Fieber

2015

Front. Aging Neurosci.

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“…With aging there is impairment of regulatory systems such as autophagy and redox homeostasis at the NMJ, which can lead to reactive oxygen species (ROS) accumulation followed by organelle damage and cell death (Li et al 2018; Stefanatos and Sanz 2018). Synaptic plasticity, which allows for the maintenance of functional activity to protect against degeneration, can decline during aging, resulting in decreased neuronal responsiveness and synaptic deterioration (Bergado and Anlmaguer 2002; Kempsell and Fieber 2015; Wagner et al 2015).…”

Section: Introductionmentioning

confidence: 99%

FOXO regulates neuromuscular junction homeostasis duringDrosophilaaging

Birnbaum

Chang

Bai

2020

Preprint

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15The transcription factor FOXO is a known regulator of lifespan extension and tissue 16 homeostasis. It has been linked to the maintenance of neuronal processes across many species, and 17 has been shown to promote youthful characteristics by regulating cytoskeletal flexibility and 18 synaptic plasticity at the neuromuscular junction (NMJ). However, the role of FOXO in aging 19 neuromuscular junction function has yet to be determined. We profiled adult Drosophila null mutant abdominal ventral longitudinal muscles and found that young mutants exhibited 21 morphological profiles similar to those of aged wild-type flies, such as larger bouton areas and 22 shorter terminal branches. We also observed changes to the axonal cytoskeleton and an 23 accumulation of late endosomes in FOXO null mutants and motor neuron-specific FOXO 24 knockdown flies, similar to those of aged wild-types. Motor neuron-specific overexpression of 25 FOXO can delay age-dependent changes to NMJ morphology, suggesting FOXO is responsible 26 for maintaining NMJ integrity during aging. Through genetic screening, we identify several 27 downstream factors mediated through FOXO-regulated NMJ homeostasis, including genes 28 involved in the p38-MAPK pathway. Interestingly, the phosphorylation of p38 and ERK were 29 increased in the motor neuron-specific FOXO knockdown flies, suggesting FOXO acts as a 30 suppressor of MAPK activation. Our work reveals that FOXO is a key regulator for NMJ 31 homeostasis, and it maintains NMJ integrity by repressing MAPK signaling during aging.32 Introduction 33 Aging involves the progressive functional decline of cellular mechanisms and tissue 34 integrity (Rose 1994; Partridge and Barton 1996; Lopez-Otin et al 2013) In the adult brain, this 35 results in a gradual decline of synaptic contacts to skeletal muscle tissue, resulting in a loss of 36 strength and muscle mass (Hall and Sanes 1993). The neuromuscular junction (NMJ) serves as the 37 synaptic interface between the branched terminals of motor neurons and the skeletal muscle fibers 38 (Punga and Ruegg 2012). The NMJ is highly dynamic in response to cellular signals and stressors, 39 and a dysregulation of molecular processes in both the pre-and post-synaptic regions can lead to 40 the onset of neurodegenerative diseases (Gonzalez-Freire et al 2014; Monani and De Vivo 2014). 41 With aging there is impairment of regulatory systems such as autophagy and redox homeostasis at 42 the NMJ, which can lead to reactive oxygen species (ROS) accumulation followed by organelle 43 damage and cell death (Li et al 2018; Stefanatos and Sanz 2018). Synaptic plasticity, which allows 44 for the maintenance of functional activity to protect against degeneration, can decline during aging, 45 resulting in decreased neuronal responsiveness and synaptic deterioration (Bergado and 46 Anlmaguer 2002; Kempsell and Fieber 2015; Wagner et al 2015).47 76 1995; Liu et al 2013). These results indicate that FOXO is an important regulator of neuronal 77 function, and that it has influence on...

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An age-related decline in the cholinergic synaptic response may cause the firing pattern in the jaw-closing motor neurons, which resembles the aversive taste response in the feeding behavior of old Aplysia kurodai

2022

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Anorexia due to aging is recognized as a syndrome of animal feeding behavior. Age-related functional disorders of the brain often cause behavioral changes. We used Aplysia kurodai to study this neural mechanism, following our previous study on food preference behaviors. The age of each wild animal was defined by a previously described method, and a significant age-related decline in food intake was observed. In this study, we explored the effects of aging on a specific inhibitory synaptic response in jaw-closing (JC) motor neurons produced by cholinergic multiaction (MA) neurons, the size of which determines the delay between MA and JC firings and this delay is reduced during aversive taste responses; in our analyses, we found a significant age-related decline in the synaptic response. Thereafter, we further explored whether such functional decline affects the JC firing pattern during the normal feeding response. During the feeding-like rhythmic responses induced by electrical nerve stimulation, the firing of the JC motor neurons advanced toward that of the MA burst, which typically happens during aversive taste responses. These results suggest that the age-related decline in the cholinergic synaptic response may partly cause the JC firing patterns that resemble the aversive taste response in old animals.

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Aging in Sensory and Motor Neurons Results in Learning Failure in Aplysia californica

Cited by 24 publications

References 70 publications

Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica

Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica

FOXO regulates neuromuscular junction homeostasis duringDrosophilaaging

An age-related decline in the cholinergic synaptic response may cause the firing pattern in the jaw-closing motor neurons, which resembles the aversive taste response in the feeding behavior of old Aplysia kurodai

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