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11. Uhl, M.A., Biery, M., Craig, N., and 14. Keniry, M.E., Kemp, H.A., Rivers, D.M., and by systematic analysis of protein complexes. Johnson, A.D. (2003). Haploinsufficiency-based Sprague, G.F., Jr. (2004). The identification of Nature 415, 141–147. large-scale forward genetic analysis of Pcl1-interacting proteins that genetically 18. Huang, D., Friesen, H., and Andrews, B. (2007). filamentous growth in the diploid human interact with Cla4 may indicate a link between Pho85, a multifunctional cyclin-dependent fungal pathogen C.albicans. EMBO J. 22, G1 progression and mitotic exit. Genetics 166, protein kinase in budding yeast. Mol. Microbiol. 2668–2678. 1177–1186. 66, 303–314. 12. Bruno, V.M., Kalachikov, S., Subaran, R., 15. Cullen, P.J., and Sprague, G.F., Jr. (2012). Nobile, C.J., Kyratsous, C., and Mitchell, A.P. The regulation of filamentous growth in yeast. (2006). Control of the C. albicans cell wall Genetics 190, 23–49. 200B Mellon Institute, Department of damage response by transcriptional regulator 16. Singh, S.D., Robbins, N., Zaas, A.K., Cas5. PLoS Pathog. 2, e21. Schell, W.A., Perfect, J.R., and Cowen, L.E. Biological Sciences, Carnegie Mellon 13. Rauceo, J.M., Blankenship, J.R., Fanning, S., (2009). Hsp90 governs echinocandin resistance University, 4400 Fifth Avenue, Pittsburgh, Hamaker, J.J., Deneault, J.S., Smith, F.J., in the pathogenic yeast Candida albicans via PA 15213, USA. Nantel, A., and Mitchell, A.P. (2008). Regulation calcineurin. PLoS Pathog. 5, e1000532. *E-mail: [email protected] of the Candida albicans cell wall damage 17. Gavin, A.C., Bosche, M., Krause, R., Grandi, P., response by transcription factor Sko1 and Marzioch, M., Bauer, A., Schultz, J., Rick, J.M., PAS kinase Psk1. Mol. Biol. Cell 19, Michon, A.M., Cruciat, C.M., et al. (2002). 2741–2751. Functional organization of the yeast proteome DOI: 10.1016/j.cub.2012.02.037

Olfactory Coding: Tagging and Tuning groups of projection . These firing patterns are also segmented into Odor-Activated for Memory a sequence of time bins by w20 Hz oscillations generated in the [8–11]. Intensely spiking A recent study in the locust olfactory system shows how neuromodulators can projection neurons carry this alter the rules of synaptic plasticity to form associative memories through the information from the antennal lobe to use of ‘tagged’ synapses. the calyx of the mushroom body, where huge numbers of Kenyon cells respond Zane N. Aldworth and Mark Stopfer believed to help encode odors to the odor sparsely with spikes that and form memories. But the are few and far between [12,13]. Scents evoke vivid recollections — the odor-evoked spiking was ephemeral; Kenyon cells are influenced by the smell of sunscreen brings the ocean it ended several seconds before oscillatory patterning generated in to mind; a whiff of perfume calls forth a rewarding drop of sugar water the antennal lobe [9] and transmit a long-ago friend. It seems effortless was presented to the animal, long the oscillations to postsynaptic to form and remember powerful after the millisecond-scale time targets, including the mushroom connections between odors and other window for STDP had closed [4]. body’s b-lobes [14]. sensory stimuli. Yet, a physiological Behavioral tests showed this training Cassenaer and Laurent [3] had understanding of how our brains procedure induced new memories, previously shown that STDP can occur instantiate these associations remains but because pre- and post-synaptic at the between Kenyon cells elusive. Hebb famously suggested [1] spiking linking odor and reward and b-lobe neurons in the locust. This that a synapse could be strengthened could not occur in these cells with first demonstration of STDP in an when the presynaptic and postsynaptic the required timing, STDP alone invertebrate showed that STDP acts neurons are activated together. The could not be responsible for forming here as a homeostatic mechanism, discovery of spike-timing-dependent them. How to resolve this dilemma? maintaining the integrity of the plasticity (STDP) [2], a process that An elegant new study by Cassenaer oscillatory signal passed along from can either increase synaptic strength and Laurent [5] points to a solution: the antennal lobe, rather than as (when the presynaptic cell is activated STDP can ‘tag’ an odor-activated a mechanism of memory. But in their milliseconds before the postsynaptic synapse, signifying and sustaining new work, Cassenaer and Laurent [5] cell), or decrease synaptic strength its identity until the reinforcement returned to the Kenyon cell–b-lobe (when the timing is reversed), provided signal arrives. synapse to explore whether a physiological mechanism for this Because the insect olfactory system STDP there can be mnemonic. The plasticity. STDP has been shown to is relatively simple and accessible it authors first characterized responses occur in many species, including the has become a useful model for the of b-lobe neurons to a range of locust [3]. study of sensory processing and odorants believed relevant to behaving Connecting Hebbian STDP to the associative memory [6]. Odors are locusts. Consistent with previous formation of memory, however, has transduced by odorant receptors and studies [3,14], the authors found that been surprisingly difficult, partly their associated olfactory receptor the temporally patterned spiking because STDP operates at much neurons in the antennae (Figure 1A) responses of b-lobe neurons varied shorter time scales than the behavioral [7]. These afferent neurons carry with the odor, and that firing rates of the experiences that lead to new information to the antennal lobe, where b-lobe neuron vastly exceeded those memories. For example, a recent study lateral interactions among the receptor of their presynaptic Kenyon cells. showed that in moths, animals that neurons, local neurons and projection The authors also found individual readily learn to associate odors with neurons rearrange odor-evoked b-lobe neurons responded much less a tasty reward, odors reliably evoke responses into temporally structured selectively to odorants than did spiking in Kenyon cells, neurons long patterns of spiking distributed across individual Kenyon cells, and that their Current Biology Vol 22 No 7 R228

A S1 S2 BCcells was activated at delays much dt>0 dt<0 Response to Odor 1 longer than the STDP window bLN bLN At first KCs S1 S1 After Odor 2 + OCT S2 (stimulation at site S2 in Figure 1A,B) MB Calyx S2 After Odor 1 + OCT STDP STDP did not affect synaptic strength. bLN bLN S1 S1 S2 S2 These results revealed a new STDP + OCT STDP + OCT property of STDP: even though Antenna bLN bLN + S1 S1 + S2 S2 octopamine had spread throughout bLNs Test Test the b-lobe, its neuromodulatory ORNs S1 S2 S1 S2 MB β Lobe + effect occurred only at synapses

-/+ bLN Response Rate PN that had been ‘tagged’ earlier by STDP. Avg EPSP Time Time Cassenaer and Laurent [5] found the + LN Before STDP STDP–octopamine modulation could Test EPSP After STDP take place when the b-lobe neurons Antennal Lobe After STDP + OCT Time Current Biology were activated by odorants rather than by current injection: odor-evoked b Figure 1. Neuromodulation of STDP in the insect olfactory system. firing rates of -lobe neurons dropped significantly after that odor (A) The locust olfactory system receives sensory input from olfactory receptor neurons (ORNs) mainly on the antennae. These neurons synapse with both local neurons (LNs) and projection had been paired with octopamine neurons (PNs) in the antennal lobe (AL), the first olfactory center within the brain. The PNs alone injection (Figure 1C). This reduction carry olfactory information to other areas of the brain, including the Kenyon cells (KCs) of the reflected a specific decrease in mushroom body calyx (MB calyx), which in turn synapse on the b-lobe neurons (bLNs). (B) synaptic strength that the modulator Spike-timing-dependent plasticity (STDP) was elicited at the KC–bLN synapse. Two well-sepa- induced between STDP-tagged rated groups of KCs in the mushroom body (MB; S1 and S2, one for pairing, one for control) presynaptic Kenyon cells and b-lobe could be activated extracellularly, and individual bLNs could be activated intracellularly. To elicit STDP, stimuli to KCs and bLNs were paired, forward (dt > 0) or backward (dt < 0), within narrow neurons; a control experiment in temporal windows (630 ms, upper sets of traces). Induction of STDP was sometimes followed which other odorants were paired by injection of octopamine (OCT) into the b lobe (middle trace). The results of these manipula- with the octopamine injection did not tions were tested afterward (bottom traces): STDP facilitated the KC-elicited response in the show this reduction. Since the bLN (rising phase of the EPSP is shown) when dt > 0, and diminished the response when dt < connections b-lobe neurons make 0; delayed delivery of OCT decreased EPSPs elicited only at STDP-tagged synapses (S1). (C) with other b-lobe neurons are In a more naturalistic test, firing in the bLNs elicited by an odor (odor 1) was reduced after that odor specifically (odor 1, but not odor 2) had been paired with OCT injection into the b-lobe. inhibitory, the authors suggested the decrease in spiking associated with octopamine reinforcement would spikes occurred at a favored phase But could STDP contribute to cause the as-yet unidentified position of the oscillatory cycle. associative memory? To test this postsynaptic targets of tagged b-lobe To test whether these responses Cassenaer and Laurent [5] delivered neurons to increase their odor-evoked were consistent with known properties current pulses extracellularly to elicit spiking. of the mushroom body circuit, spikes in presynaptic Kenyon cells Together, these results could Cassenaer and Laurent [5] devised and intracellularly to elicit spikes in resolve the timing mismatch a computational model including b-lobe neurons (Figure 1B). By varying exemplified by the experiments in connectivity and STDP rules known the timing of these paired stimuli, the moths [4]: octopamine release, even to exist between Kenyon cells and authors confirmed the STDP rules if delayed beyond the narrow STDP b-lobe neurons. The model gave mixed they had previously characterized in window, could specifically modulate results: it could reproduce the phase the locust. Now they added a new those odor-specific synapses earlier of firing seen in b-lobe neurons in vivo, ingredient: the neuromodulator tagged through STDP. By changing but could not reproduce response octopamine, which is believed to be the rules of STDP, octopamine probability or the extent of response released throughout the insect brain could allow a well-described form of saturation across the population of as a reward signal when the animal Hebbian plasticity to serve as the b-lobe neurons. This mismatch consumes an appetitive stimulus like neural mechanism for memory between model and brain suggested sugar water [15]. Remarkably, injecting formation. a page was missing from the STDP a tiny squirt of octopamine into the This exciting work opens several rulebook. The authors thus launched b-lobe one second after an STDP enticing new avenues of inquiry. One a set of experiments to learn more pairing (stimulation at site S1 in particularly interesting question will about the b-lobe neurons. Figure 1A,B) caused a reliable be to test whether different types of Simultaneous intracellular recordings decrease in the size of the response neurons play by different rules. In from pairs of b-lobe neurons revealed that Kenyon cell activation triggered in Drosophila, for example, different something new: about one of every the b-lobe neuron. This decrease subpopulations of Kenyon cells are four pairs was interconnected by occurred whether the timing of the required at different times for memory inhibitory synapses. Adding lateral Kenyon cell–b-lobe neuron pairing acquisition and retrieval [16].In inhibition to the model brought its would otherwise have led to increased addition, while the b-lobe neurons results into close agreement with or decreased synaptic strength in the characterized by Cassenaer and experimental data and, further, showed absence of the neuromodulator. A Laurent [5] appear to be inhibitory, that the b-lobe neurons maximize their control procedure in which other neurons in the b-lobe may be available dynamic range for coding octopamine was delivered, but in excitatory; the properties and odors. which a different population of Kenyon projection sites of all neurons of the Dispatch R229 b-lobe remain to be revealed. The story References coding in an olfactory system. J. Neurosci. 27, 1. Hebb, D.O. (1949). The Organization of 1659–1669. of STDP within the mushroom body, Behavior: A Neuropsychological Theory 13. Perez-Orive, J., Mazor, O., Turner, G.C., already rich and complex, is just (New York: Wiley). Cassenaer, S., Wilson, R.I., and Laurent, G. beginning. 2. Markram, H., Lubke, J., Frotscher, M., and (2002). Oscillations and sparsening of odor Sakmann, B. (1997). Regulation of synaptic representations in the mushroom body. It will be important to know how efficacy by coincidence of postsynaptic APs Science 297, 359–365. neuromodulators like octopamine and EPSPs. Science 275, 213–215. 14. MacLeod, K., Backer, A., and Laurent, G. 3. Cassenaer, S., and Laurent, G. (2007). Hebbian (1998). Who reads temporal information affect other points within the STDP in facilitates the contained across synchronized and oscillatory olfactory system. Octopaminergic synchronous flow of olfactory information in spike trains? Nature 395, 693–698. neurons are widely branching, locusts. Nature 448, 709–713. 15. Hammer, M., and Menzel, R. (1998). Multiple 4. Ito, I., Ong, R.C., Raman, B., and Stopfer, M. sites of associative odor learning as revealed extending into the antennal lobe and (2008). Sparse odor representation and by local brain microinjections of octopamine the mushroom body [17]. Although olfactory learning. Nat. Neurosci. 11, in honeybees. Learn. Mem. 5, 146–156. 1177–1184. 16. Krashes, M.J., Keene, A.C., Leung, B., Cassenaer and Laurent [5] restricted 5. Cassenaer, S., and Laurent, G. (2012). Armstrong, J.D., and Waddell, S. (2007). application of octopamine to the Conditional modulation of spike-timing- Sequential use of mushroom body neuron b-lobe, it will be interesting to dependent plasticity for olfactory learning. subsets during drosophila odor memory Nature 482, 47–52. processing. Neuron 53, 103–115. evaluate its other effects, which may 6. Menzel, R., and Muller, U. (1996). Learning and 17. Braunig, P. (1991). Suboesophageal DUM be systemic, and may affect the ways memory in honeybees: from behavior to neural neurons innervate the principal neuropiles of substrates. Annu. Rev. Neurosci. 19, 379–404. the locust brain. Phil. Trans. R. Soc. Lond. B output from the mushroom body is 7. Vosshall, L.B., Amrein, H., Morozov, P.S., 332, 221–240. interpreted downstream. It will be Rzhetsky, A., and Axel, R. (1999). A spatial map 18. Frey, U., and Morris, R.G. (1997). Synaptic interesting as well to explore of olfactory receptor expression in the tagging and long-term potentiation. Nature 385, Drosophila antenna. Cell 96, 725–736. 533–536. mechanisms by which STDP tags 8. Ito, I., Bazhenov, M., Ong, R.C., Raman, B., and 19. Murase, S., Mosser, E., and Schuman, E.M. synapses, particularly with respect Stopfer, M. (2009). Frequency transitions in (2002). Depolarization drives beta-catenin into odor-evoked neural oscillations. Neuron 64, neuronal spines promoting changes in to possibly analogous 692–706. synaptic structure and function. Neuron 35, tagging mechanisms observed in 9. Laurent, G., and Davidowitz, H. (1994). 91–105. mammals [18,19]. The recent Encoding of olfactory information with 20. Simoes, P., Ott, S.R., and Niven, J.E. (2011). oscillating neural assemblies. Science 265, Associative olfactory learning in the desert development of a behavioral 1872–1875. locust, Schistocerca gregaria. J. Exp. Biol. 214, paradigm for assessing associative 10. Stopfer, M., Bhagavan, S., Smith, B.H., and 2495–2503. Laurent, G. (1997). Impaired odour learning in locusts [20] will allow discrimination on desynchronization of researchers to tackle these problems odour-encoding neural assemblies. Nature 390, NIH-NICHD, Building 35, 35 Lincoln Drive, from physiology to behavior in 70–74. Room 3A-102, msc 3715, Bethesda, 11. Tanaka, N.K., Ito, K., and Stopfer, M. (2009). a single animal. This will be an MD 20892 USA. Odor-evoked neural oscillations in Drosophila E-mail: [email protected] important step to understanding are mediated by widely branching interneurons. J. Neurosci. 29, 8595–8603. the formation of associative 12. Jortner, R.A., Farivar, S.S., and Laurent, G. memories. (2007). A simple connectivity scheme for sparse DOI: 10.1016/j.cub.2012.02.047

Microtubule Organization: A cytoskeleton accomplished? A new study published in this issue of Pericentriolar Material-Like Structure Current Biology [4] shows that the transient generation of a novel in Yeast Meiosis microtubule organizing center called the radial microtubule organizing center (rMTOC) underlies formation During meiotic prophase in fission yeast, the nucleus undergoes dramatic of the radial microtubule array during oscillatory movements. A newly identified structure, the radial microtubule meiotic prophase. organizing center (rMTOC), mediates these movements and shares some Performing EM tomographic of the features of the pericentriolar material in higher eukaryotes. reconstructions of cells undergoing meiotic prophase, Funaya et al. [4] Alexander Dammermann1, so-called horsetail movements, which made the exciting observation that Lubos Cipak1,2, and Juraj Gregan1,* have been shown to be important for microtubules do not emanate directly meiotic recombination and proper from the spindle pole bodies as The microtubule cytoskeleton segregation of chromosomes [2,3]. previously thought, but rather from an undergoes dramatic rearrangements This process requires conversion electron-dense area located a distance during the cell cycle in order to create of interphase microtubule bundles of 30–180 nm away from the spindle various specialized structures such as generated from multiple microtubule pole body. They call this area the the mitotic spindle [1]. During prophase organizing centers (MTOCs) into radial microtubule organizing center of fission yeast meiosis, microtubules a single radial microtubule (rMT) array. (rMTOC). This observation was are reorganized to form a single radial At the end of prophase, microtubules unexpected because previous studies array associated with the spindle pole need to be reorganized again to showed interphase microtubules to be body (SPB), the yeast centrosome allow formation of a bipolar spindle located in close proximity to the equivalent. This structure facilitates (Figure 1). How are these dramatic spindle pole body [5]. What do we know oscillatory movements of the nucleus, reorganizations of microtubule about this rMTOC and how is it