NO Honey, I Don't Remember

Nitric oxide (NO) is a soluble gas that acts as a novel type of intercellular messenger molecule in the brain (Bredt and Snyder 1992). NO has been suggested to play a role in learning and memory (Table 1) and in types of neuronal plasticity thought to contribute to learning, including both long-term potentiation (LTP) in hippocampus and long-term depression (LTD) in cerebellum (for reviews seeHawkins et al. 1994; Zhuo and Hawkins 1995). However, the involvement of NO in mammalian learning, LTP, and LTD is controversial (Bannerman et al. 1994a; Bannerman et al. 1994b; Linden and Connor 1992), and the balance of the evidence has shifted back and forth. In this issue of Neuron, U. Müller 1996 describes experiments in which he took a new approach to this problem by using the honeybee to investigate the function of NO. He reports that there are several different memory systems that are engaged by different numbers of training trials and that cover different (but overlapping) time spans in honeybee. Inhibition of NO synthase (NOS) during training blocks only one of these: long-term (24 hr) memory following multiple training trials. NOS inhibitors have no effect on initial learning or medium-term (3 or 8 hr) memory and no effect on the modest level of long-term memory following a single training trial. Thus, in honeybee, NO seems to be critically involved in only one type of memory: long-term memory following repeated training trials. This conclusion is reminiscent of similar conclusions about the role of the transcription factor CREB in long-term memory in Aplysia, Drosophila, and mice (reviewed byFrank and Greenberg 1994), and Müller speculates that NO might act via CREB in honeybee. Consistent with this idea, NO is thought to act via CREB in mammalian PC12 cells (Peunova and Enlikolopov 1993).