RESEARCH HIGHLIGHTS NEUROTRANSMISSION Exploring profilin DOI: 10.1038/nrn2182 Surprisingly, they found that Pfn2–/– mice, pointing towards a Pfn2–/– mice displayed normal higher vesicle release probability. development and brain anatomy. Immunoprecipitation and EM studies Learning and memory, long-term also indicated that the number of potentiation (LTP) and long-term docked vesicles is approximately 25% depression (LTD) were not impaired higher in Pfn2–/– mice. in Pfn2–/– mice when compared with How does profilin 2 alter vesicle control mice. These results suggest release? When neurotransmitter that profilin 2 is not required for secretion was stimulated in cortical development, synaptic plasticity or synaptosomes from control mice, learning and memory. F-actin levels were significantly The authors noticed, however, increased. This did not occur in that the Pfn2–/– mice behaved synaptosome preparations from differently to control mice. They Pfn2–/– mice. In addition, profilin 2, were hyperactive, and they showed but not profilin 1, was shown to be elevated exploratory and novelty- tightly associated with the WAVE- Profilins are regulators of actin seeking behaviour when placed into complex, a protein complex that is polymerization. Profilin 2 is a new environment. This included implicated in actin dynamics and expressed mainly in neurons, but increased locomotor activity, wall is abundant in synaptosomal prepa- its specific function is unknown. A rearings and rearings in the centre of rations. The authors therefore study by Boyl et al. provides evidence the experimental area. Conversely, suggest that WAVE and profilin 2 that profilin 2 is required for activ- in the familiar environment of their might cooperate to restrict synaptic ity-stimulated actin polymerization home cage, they showed reduced vesicle release. in the synapse, which controls locomotor activity compared with These results show that profilin 2 neurotransmitter release, neuronal control mice. is crucial for actin polymerization excitability and novelty-seeking Locomotor and exploratory at the synapse, which might provide behaviour in mice. behaviour are known to be mediated a physical barrier to vesicle release. There are four mammalian by the striatum. Ultrastructural Future studies focussing on the profilin isoforms, all of which are analysis of this brain region showed downstream signalling pathways G-actin binding proteins. Profilins are differences in the organization used by profilin 1 and profilin 2 will implicated in the actin dynamics that of synapses when Pfn2–/–and further contribute to our understand- control membrane trafficking events wild-type mice were compared. ing of neurotransmitter release and such as vesicle endo- and exocytosis. Electrophysiological recordings from the role of actin in this process. Brain cells express profilin 2, but the striatal spiny neurons showed that Claudia Wiedemann role of this protein in brain function the frequency of miniature excitatory is not well understood. The authors postsynaptic currents (mEPSPs) was ORIGINAL RESEARCH PAPER Boyl, P. P. et al. therefore used profilin 2-knockout slightly higher, indicating that more Profilin2 contributes to synaptic vesicle mice (Pfn2–/–) to investigate the effects vesicles at striatal Pfn2–/– synapses exocytosis, neuronal excitability, and novelty- seeking behaviour. EMBO J. 31 May 2007 of profilin 2 at anatomical, electro- were released. Furthermore, paired- (doi:10.1038/sj.emboj.7601737) physiological and behavioural levels. pulse facilitation was decreased in NATURE REVIEWS | NEUROSCIENCE VOLUME 8 | JULY 2007 © 2007 Nature Publishing Group .