Abstract
Evidence from invertebrate systems including Aplysia and Drosophila, as well as studies carried out with mammalian brain, suggests that Ca2+-sensitive adenylyl cyclases may be important for long-term synaptic changes and learning and memory. Furthermore, some forms of long-term potentiation (LTP) in the hippocampus elevate cyclic AMP (cAMP) signals, and activation of adenylyl cyclases and cAMP-dependent protein kinase may be required for late stages of LTP. We propose that long-term changes in neurons and at synapses may require synergism between the cAMP and Ca2+ signal transduction systems which regulates transcription and synthesis of specific proteins required for long-term synaptic changes. During LTP, protein kinase C is activated and intracellular Ca2+ increases. We hypothesize that the calmodulin (CaM)-regulated adenylyl cyclases may be activated during LTP because of increases in intracellular Ca2+, release of free CaM from neuromodulin, activation by protein kinase C, release of neurotransmitters, or a combination of these events. Synergistic activation of CaM-sensitive adenylyl cyclases may produce a robust or prolonged cAMP signal required for transcriptional control. Furthermore, the coupling of the Ca2+ and cAMP systems may provide positive feedback regulation of Ca2+ channels by cAMP-dependent protein kinase.
Original language | English |
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Pages (from-to) | 429-440 |
Number of pages | 12 |
Journal | Behavioral and Brain Sciences |
Volume | 18 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1995 |
Externally published | Yes |
Keywords
- adenylyl cyclase
- cAMP
- calcium
- calmodulin
- long-term potentiation
- neuroplasticity
ASJC Scopus subject areas
- Neuropsychology and Physiological Psychology
- Physiology
- Behavioral Neuroscience