{'fraction_non_alphanumeric': 0.03110419906687403, 'fraction_numerical': 0.013996889580093312, 'mean_word_length': 5.795774647887324, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Spike Frequency Decoding and Autonomous Activation of Ca2+–Calmodulin-Dependent Protein Kinase II in Dorsal Root Ganglion Neurons

Autonomous activation of calcium–calmodulin kinase (CaMKII) has been proposed as a molecular mechanism for decoding Ca2+ spike frequencies resulting from action potential firing, but this has not been investigated in intact neurons. This was studied in mouse DRG neurons in culture using confocal measurements of [Ca2+]i and biochemical measurements of CaMKII autophosphorylation and autonomous activity. Using electrical stimulation at different frequencies, we find that CaMKII autonomous activity reached near maximal levels after ∼45 impulses, regardless of firing frequency (1–10 Hz), and autonomous activity declined with prolonged stimulation. Frequency-dependent activation of CaMKII was limited to spike frequencies in the range of 0.1–1 Hz, despite marked increases in [Ca2+]i at higher frequencies (1–30 Hz). The high levels of autonomous activity measured before stimulation and the relatively long duration of Ca2+ spikes induced by action potentials (∼300 msec) are consistent with the lower frequency range of action potential decoding by CaMKII. The high autonomous activity under basal conditions was associated with extracellular [Ca2+], independently from changes in [Ca2+]i, and unrelated to synaptic or spontaneous impulse activity. CaMKII autonomous activity in response to brief bursts of action potentials correlated better with the frequency of Ca2+ transients than with the concentration of [Ca2+]i. In conclusion, CaMKII may decode frequency-modulated responses between 0.1 and 1 Hz in these neurons, but other mechanisms may be required to decode higher frequencies. Alternatively, CaMKII may mediate high-frequency responses in subcellular microdomains in which the enzyme is maintained at a low level of autonomous activity or the Ca2+ transients have faster kinetics.