Behavioral aging is associated with reduced sensory neuron excitability in Aplysia californica

Abstract

Invertebrate models have advantages for understanding the basis of behavioral aging due to their simple nervous systems and short lifespans. The potential usefulness of Aplysia californica in aging research is apparent from its long history of neurobiological research, but it has been underexploited in this model use. Aging of simple reflexes at both single sensory neuron and neural circuit levels was studied to connect behavioral aging to neurophysiological aging. The tail withdrawal reflex (TWR), righting reflex, and biting response were measured throughout sexual maturity in 3 cohorts of hatchery-reared animals of known age. Reflex times increased and reflex amplitudes decreased significantly during aging. Aging in sensory neurons of animals with deficits in measures of the TWR and biting response resulted in significantly reduced excitability in old animals compared to their younger siblings. The threshold for firing increased while the number of action potentials in response to depolarizing current injection decreased during aging in sensory neurons, but not in tail motoneurons. Glutamate receptor-activated responses in sensory neurons also decreased with aging. In old tail motoneurons, the amplitude of evoked EPSPs following tail shock decreased, presumably due to reduced sensory neuron excitability during aging. The results were used to develop stages of aging relevant to both hatchery-reared and wild-caught Aplysia. Aplysia is a viable aging model in which the contributions of differential aging of components of neural circuits may be assessed.

Taste‐related sensations in old age

“…Investigations on the central nervous system structures with crucial roles in cognitive processing have shown age‐related alteration of intrinsic neuronal excitability . Consistent with this hypothesis, ageing neurons have been observed undergoing structural changes such as decreases in soma size , loss/regression of dendrites and loss of dendritic spines , loss of synapses , alterations in neurotransmitter receptors and/or decreased response to neurotransmitters . Changes in neuronal physiology and structure lead to a less efficient transmission of information encoded in the form of action potentials and impairment of the computational efficacy of the neuronal network .…”

Phospholipase A2 – nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment

“…In addition, Janse et al (1999) showed a correlation between reproductive senescence and reduced electrical excitability of the caudodorsal cells (CDCs), neuroendocrine cells producing Lymnaea’s ovulation hormone and other neuropeptides involved in the regulation of reproductive behavior ( Janse et al, 1999 ). In Aplysia , studies from the Peretz lab and a recent study by Kempsell and Fieber (2014) have linked age-associated behavioral and homeostatic deficiencies to declining neuronal excitability ( Rattan and Peretz, 1981 ; Peretz, 1988 ; Skinner and Peretz, 1989 ). Interestingly, in the nematode C. elegans age-associated decline in chemotactic behavior is associated with a decline in sensory neuron excitability due to oxidation-induced enhancement of voltage-gated K + currents ( Cai and Sesti, 2009 ; Sesti et al, 2010 ).…”

Dissecting mechanisms of brain aging by studying the intrinsic excitability of neurons

“…Investigations on the central nervous system (CNS) structures with crucial roles in cognitive processing have shown age-related alteration of intrinsic neuronal excitability (Landfield and Pitler, 1984 ; Disterhoft and Oh, 2007 ; Matthews et al, 2009 ; Oh et al, 2010 ; Wang et al, 2011 ). Consistent with this idea, aging neurons have been observed undergoing structural changes such as decreases in soma size (de Brabander et al, 1998 ; Wong et al, 2000 ; Figure 1 ), loss/regression of dendrites and loss of dendritic spines (Jacobs et al, 1997 ; Peters et al, 1998 ; Page et al, 2002 ; Duan et al, 2003 ; Figure 1 ), loss of synapses (Chen et al, 1995 ; Wong et al, 1998 ; Figure 1 ), alterations in neurotransmitter receptors (Post-Munson et al, 1994 ; Rosene and Nicholson, 1999 ; Figure 1 ) and/or decreased response to neurotransmitters (Fieber et al, 2010 ; Akhmedov et al, 2013 ; Kempsell and Fieber, 2014 ). Changes in neuronal physiology and structure lead to a less efficient transmission of information encoded in the form of action potentials (APs; Chang et al, 2005 ; Luebke and Chang, 2007 ) and impairment of the computational efficacy of the neuronal network (Randall et al, 2012 ).…”

“…AP threshold is the critical level to which the membrane potential must be depolarized in order to initiate an AP and hence it is often used as a measure for neuron excitability. Recent studies have reported an age-related increase in the AP threshold of the rat hippocampal CA1 pyramidal cell (HP-CA1-PC; Matthews et al, 2009 ) and primary somatosensory cortex layer 3 pyramidal cell (S1-PC) (Hickmott and Dinse, 2013 ), mice (Randall et al, 2012 ) and rabbit HP-CA1-PC (Power et al, 2002 ) and also in the ventral pleural ganglion sensory neuron (PVC-SN) and buccal ganglion sensory neuron (BSC-SN) of aging Aplysia (Kempsell and Fieber, 2014 ). While the basis of this change has not yet been clarified, age-related depolarization of the AP threshold could likely be ascribed to alterations of voltage-gated Na + channel (Na v channel) activation properties or channel subtype expression patterns (Randall et al, 2012 ).…”