High neural activity accelerates the decline of cognitive plasticity with age in Caenorhabditis elegans

Abstract

The ability to learn progressively declines with age. Neural hyperactivity has been implicated in impairing cognitive plasticity with age, but the molecular mechanisms remain elusive. Here, we show that chronic excitation of the Caenorhabditis elegans O2-sensing neurons during ageing causes a rapid decline of experience-dependent plasticity in response to environmental O2 concentration, whereas sustaining lower activity of O2-sensing neurons retains plasticity with age. We demonstrate that neural activity alters the ageing trajectory in the transcriptome of O2-sensing neurons, and our data suggest that high-activity neurons redirect resources from maintaining plasticity to sustaining continuous firing. Sustaining plasticity with age requires the K+-dependent Na+/Ca2+ (NCKX) exchanger, whereas the decline of plasticity with age in high-activity neurons acts through calmodulin and the scaffold protein Kidins220. Our findings demonstrate directly that the activity of neurons alters neuronal homeostasis to govern the age-related decline of neural plasticity and throw light on the mechanisms involved.

Regulation of longevity by depolarization-induced activation of PLC-β–IP 3 R signaling in neurons

“…Our data reveal a signaling circuit that actuates the relationship between glutamatergic excitability and organismal lifespan (Fig. 4H) (7,8). The crux of this model is our finding that depolarization increases the gain of PLC-β-IP 3 R signaling.…”

“…1I). Thus, depolarization augments PIP 2-PLC-β1 association such that subsequent Hyperexcitability of glutamatergic neurons induces premature aging and shortens lifespan in many organisms (7,8). Since inhibition of the Na + /K + ATPase potentiated PLC-β-IP 3 R signaling in N2a cells (Fig.…”

The Developmental Phosphoproteome of Fasciola Gigantica by Shotgun

“…While in F. hepatica, the FhCaMs functioned as a Ca 2+ modulator was proved to be important for the growth and movement of juvenile uke [42,43]. Recent research clari ed calmodulin of Caenorhabditis elegans was implicated in the plasticity impairment of high-activity neurons with age, indicating a different but novel role in neuronal activity [44]. Furthermore, others phosphoproteins of F. gigantica annotated in more than 10 KEGG pathways were compared with other parasites (Table 1).…”

Tyraminergic corollary discharge filters reafferent perception in a chemosensory neuron

“…69 Moreover, preventing over-activation of BAG may serve as protective measure against aging and loss of neural plasticity over longer timescales. It was shown that higher neuronal activity levels can be detrimental, leading to degenerative plaque formation in humans and mice as well as loss of neural plasticity in worms, 70,71 whereas reduced BAG activity increases the worm's lifespan. 72 These responses could not be studied in standard laboratory conditions, where worms are typically held on a bare agarose surface supplied with a bacterial lawn.…”