The results of two studies indicate that PKM has an essential role in LTP and memory maintenance, adding another degree of freedom to the molecular mechanisms that underlie synaptic plasticity.
You are packed in a dimly lit, narrow hallway. It is hot and the air feels heavy from the humidity. The current of air that runs through suddenly changes to a sharp stench that can only be compared to sweaty socks. Then it happens — a current of electricity runs across the floor and jolts you over and over. A second, equally foul odour follows. You prepare for the worst, but nothing happens. Suddenly, you are slammed sideways and crammed into an even smaller space. After some jostling, the space opens into another hall. From one direction you smell socks; from the other, that second foul odour. Where to go? This is what a fly might experience in an odour-avoidance learning task that was used in one of two papers in Nature Neuroscience to unravel the role of protein kinase C (PKC) in memory and long-term potentiation (LTP).
There are three main categories of PKC molecules — conventional, novel and atypical. To add another layer of complexity, these kinases can exist in two forms — a full-length form and a truncated form that lacks the amino-terminal regulatory domain, leaving a constitutively active catalytic domain (PKM). There is evidence that one form in particular — atypical PKM — is maintained at an elevated level during the maintenance phase of LTP. But what is it doing? Drier et al. obtained evidence that the acute expression of mouse or Drosophila PKM in flies enhances memory formation after olfactory avoidance training. Curiously, PKM was not able to enhance long-term memory formation, but only affected a protein-synthesis-independent form that is referred to as anaesthesia-resistant memory. The authors argue that the enhancement of long-term memory might not be detected if PKM is crucial for memory maintenance, because the endogenous enzyme would already have been activated by training.
The experiments by Drier et al. are in agreement with work done at the cellular level by Ling et al., who show that PKM can maintain LTP over a six-hour period in rat hippocampal slices. Injection of mouse PKM into postsynaptic neurons elicited a potentiation of transmission that occluded LTP induced by synaptic activity. Moreover, manipulation of enzyme activity using a dominant-negative form of PKM enabled Ling et al. to block both the PKM-induced potentiation and the activity-dependent LTP.
The results of these two studies indicate that PKM has an essential role in LTP and memory maintenance, adding another degree of freedom to the molecular mechanisms that underlie synaptic plasticity, a field in which the focus has been centred largely on other protein kinases, such as CaMKII.
Michael Stebbins
References
Ling, D. S. F. et al. Protein kinase M is necessary and sufficient for LTP maintenance. Nature Neurosci.5, 295–296 (2002) | Article | PubMed |
Drier, E. A. et al. Memory enhancement and formation by atypical PKM activity in Drosophila melanogaster. Nature Neurosci.5, 316–324 (2002) | Article | PubMed |
Paulsen, O. & Morris, R. Flies put the buzz back into long-term-potentiation. Nature Neurosci.5, 289–290 (2002) | Article | PubMed |
has an essential role in LTP and memory maintenance, adding another degree of freedom to the molecular mechanisms that underlie synaptic plasticity.
