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

Abstract

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.

Heart rate variability and baroreflex sensitivity in bilateral lung transplant recipients

“…In fact, the outliers were the two youngest patients, who were operated when they were 22 and 28 years old, respectively, 3Á5 and 2Á7 years before our study. As nerve plasticity is more efficient in younger than in later life (Burke & Barnes, 2006;Kumar et al, 2012;Kempsell & Fieber, 2015), we speculate that three years may have been enough, in these two patients, to recover afferent neural fibres between lungs and cardiorespiratory centres. It would be interesting to repeat the experiments on these patients in 2-4 years: if the hypothesis of a gradual reinnervation of transplanted lungs holds, we would expect a progressive increase in the power of the HF peak.…”

Synapse Formation Activates a Transcriptional Program for Persistent Enhancement in the Bi-directional Transport of Mitochondria

“…We next investigated the signaling pathways that regulate transport, with a focus on three that are critical for synaptic plasticity: inositol triphosphate (IP3) (Shuai et al, 2007; Swatton and Taylor, 2002), protein kinase C (PKC) (Furukawa et al, 1995; Kempsell and Fieber, 2015), and cyclic AMP (cAMP) (Azhderian et al, 1994). Our method was to expose SNs to either ADA (adenophostin A, activator of IP3 receptor signaling, concentration 10 μM) for 10 min, PMA (phorbol 12-myristate 13-acetate, activator of PKC signaling, concentration 50 nM) for 15 min, or forskolin (FK) (activator of cAMP signaling, concentration 50 μM) for 30 min.…”

Habituation in the Tail Withdrawal Reflex Circuit is Impaired During Aging in Aplysia californica

“…The complexity of the mammalian brain makes it difficult to study aging in defined circuits and individual neurons, particularly when trying to couple changes at the neuronal level with changes in even the simplest of behaviors. Age-related neural changes in Aplysia californica ( Aplysia ), such as declines in sensory and motoneuron excitability (Kempsell and Fieber, 2014 , 2015b ) and failure to respond to second messengers (Kempsell and Fieber, 2015a ), mirror hallmarks of aging in vertebrates, but are easily studied in this model organism. Simple behaviors in Aplysia , such as habituation, can be studied in individual neurons of simple reflex circuits to better understand aging-associated effects.…”

“…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, 2015a , b ). This study addressed another form of nonassociative learning in Aplysia .…”