EVERYTHING IS WRONG

...about protein synthesis and memory formation, apparently. In keeping with the general theme of propranolol as a "memory eraser," a brand new iconoclastic paper (Canal, Chang, & Gold, 2007) claims that massive fluctuations in neurotransmitter levels (including norepinephrine, whose receptors are the target of beta blockers like propranolol; also dopamine and serotonin) -- rather than inhibition of protein synthesis (e.g., Doyere et al., 2007) -- are responsible for the amnestic quality of drugs like anisomycin:

New protein synthesis not essential to memory formation

Neuroscientist Paul E. Gold and colleagues have demonstrated that new protein synthesis is not required for long-term memory formation, a discovery that challenges basic assumptions about the mechanisms of memory....

. . .

Brain researchers have long used drugs that enhance or hinder memory formation to gain insight into the mechanisms at play. Early experiments in rats found that protein synthesis inhibitors injected into brain regions involved in memory processing could disrupt long-term memory formation. This led some to hypothesize that new protein synthesis was essential to the creation of long-term memories.

A research team led by neuroscientist Paul E. Gold discovered an alternate explanation for this effect. The researchers observed that the protein synthesis inhibitor anisomycin, which is commonly used in memory studies, causes dramatic changes in brain chemistry – apart from protein synthesis inhibition – that interfere with memory formation. They found that exposing rat brains to anisomycin sets off wild fluctuations in neurotransmitter levels in the brain region targeted in the experiment – the amygdala, one of several brain structures involved in processing memories and emotions. Large fluctuations in neurotransmitter levels in the amygdala are known to interfere with memory formation.

If this paper is correct, the results invalidate the premise of much previous research in the field [at the very least, regarding the mechanism of action for anisomycin in memory studies]. More later, hopefully...

References

Canal CE, Chang Q, Gold PE. (2007). Amnesia produced by altered release of neurotransmitters after intraamygdala injections of a protein synthesis inhibitor. Proc Natl Acad Sci. 104:12500-5.

Amnesia produced by protein synthesis inhibitors such as anisomycin provides major support for the prevalent view that the formation of long-lasting memories requires de novo protein synthesis. However, inhibition of protein synthesis might disrupt other neural functions to interfere with memory formation. Intraamygdala injections of anisomycin before inhibitory avoidance training impaired memory in rats tested 48 h later. Release of norepinephrine (NE), dopamine (DA), and serotonin, measured at the site of anisomycin infusions, increased quickly by ~1,000–17,000%, far above the levels seen under normal conditions. NE and DA release later decreased far below baseline for several hours before recovering at 48 h. Intraamygdala injections of a beta-adrenergic receptor antagonist or agonist, each timed to blunt effects of increases and decreases in NE release after anisomycin, attenuated anisomycin-induced amnesia. In addition, similar to the effects on memory seen with anisomycin, intraamygdala injections of a high dose of NE before training impaired memory tested at 48 h after training. These findings suggest that altered release of neurotransmitters may mediate amnesia produced by anisomycin and, further, raise important questions about the empirical bases for many molecular theories of memory formation.

Doyere V, Debiec J, Monfils MH, Schafe GE, Ledoux JE. (2007). Synapse-specific reconsolidation of distinct fear memories in the lateral amygdala. Nat Neurosci. 10:414-6.

When reactivated, memories enter a labile, protein synthesis–dependent state, a process referred to as reconsolidation. Here, we show in rats that fear memory retrieval produces a synaptic potentiation in the lateral amygdala that is selective to the reactivated memory, and that disruption of reconsolidation is correlated with a reduction of synaptic potentiation in the lateral amygdala. Thus, both retrieval and reconsolidation alter memories via synaptic plasticity at selectively targeted synapses.