Date Published: May 23, 2019
Publisher: Public Library of Science
Author(s): Justin B. Greer, Edward M. Mager, Lynne A. Fieber, Michelle M. Adams.
The simplified nervous system of Aplysia californica (Aplysia) allows for detailed studies of physiological and molecular changes in small sets of neurons. Sensory neurons of the biting and tail withdrawal reflexes are glutamatergic and show reduced L-Glutamate current density in aged animals, making them a good candidate to study age-related changes in glutamatergic responses. To examine if changes in ionotropic L-Glu receptor (iGluR) transcription underlie reduced physiology, mRNA expression of iGluR was quantified in two sensory neuron clusters of two cohorts of Aplysia at both sexual maturity (~8 months) and advanced age (~12 months). Sensory neuron aging resulted in a significant overall decrease in expression of iGluR subunits in both sensory neuron clusters and cohorts. Although the individual subunits differentially expressed varied between sensory neuron clusters and different cohorts of animals, all differentially expressed subunits were downregulated, with no subunits showing significantly increased expression with age. Overall declines in transcript expression suggest that age-related declines in L-Glu responsiveness in Aplysia sensory neurons could be linked to overall declines in iGluR expression, rather than dysregulation of specific subunits. In both sensory neuron clusters tested the N-methyl-D-aspartate receptor subtype was expressed at significantly greater levels than other iGluR subtypes, suggesting an in vivo role for NMDAR-like receptors in Aplysia sensory neurons.
Aging is associated with impairments in neuronal function that result in declines in cognitive function and reflex systems of aged animals. A reduced number of synaptic contacts and reduced dendritic spine density can alter the strength of synaptic connections, leading to diminished excitatory postsynaptic potential amplitude in aged neurons [1–3]. The marine mollusk Aplysia californica (Aplysia) has been used extensively as a model for studying the effects of aging due to a relatively simple nervous system, easily identifiable neurons, and short life span of ~12 months. Well-mapped neural circuits in the Aplysia nervous system have allowed researchers to more closely correlate age-related changes in reflex behaviors with physiological and molecular changes in the relevant underlying neurons [4–9].
Previous studies in Aplysia have extensively documented age-related changes in behavior, neuronal function, neurotransmitter regulation, and transcriptional regulation [4, 28–31]. In this study we used the glutamatergic PVC and BSC sensory neurons clusters to examine molecular changes that may underlie declines in L-Glu physiology with age. Although the exact function of iGluR currents in sensory neurons of Aplysia is undemonstrated, PVC and BSC clusters provide a large number of easily identifiable and homogeneous neurons that may be a model for changes in glutamatergic transmission during learning or aging. PVC and BSC sensory neurons show diminished or absent iGluR during aging, suggesting that ion channel function may be compromised. We therefore examined transcriptional changes of iGluR subunits during aging as a potential contributor to reduced L-Glu physiology.