- Email: [email protected]
Sensorimotor Neuroscience: Motor Precision Meets Vision
Current Biology
Dispatches be tested. Currently, our best estimate with the best data, and arguably the best tools, tells us sponges are the sister group to all other metazoans — we think. REFERENCES 1. Simion, P., Philippe, H., Baurain, D., Jager, M., Richter, D.J., Di Franco, A., Roure, B., Satoh, innec, E., Ereskovsky, A., et al. (2017). N., Que A large and consistent phylogenomic dataset supports sponges as the sister group to all other animals. Curr. Biol. 27, 958–967. 2. Telford, M.J., Budd, G.E., and Philippe, H. (2015). Phylogenomic insights into animal evolution. Curr. Biol. 25, R876–R887. 3. Leys, S.P., Nichols, S.A., and Adams, E.D. (2009). Epithelia and integration in sponges. Integr. Comp. Biol. 49, 167–177. 4. Dunn, C.W., Hejnol, A., Matus, D.Q., Pang, K., Browne, W.E., Smith, S.A., Seaver, E., Rouse, G.W., Obst, M., Edgecombe, G.D., et al. (2008). Broad phylogenomic sampling improves resolution of the animal tree of life. Nature 452, 745–749.
5. Philippe, H., Derelle, R., Lopez, P., Pick, K., Borchiellini, C., Boury-Esnault, N., Vacelet, J., innec, E., et al. Renard, E., Houliston, E., Que (2009). Phylogenomics revives traditional views on deep animal relationships. Curr. Biol. 19, 706–712. 6. Pisani, D., Pett, W., Dohrmann, M., Feuda, R., Rota-Stabelli, O., Philippe, H., Lartillot, N., and Wo¨rheide, G. (2015). Genomic data do not support comb jellies as the sister group to all other animals. Proc. Natl. Acad. Sci. USA 112, 15402–15407. 7. Borowiec, M.L., Lee, E.K., Chiu, J.C., and Plachetzki, D.C. (2015). Extracting phylogenetic signal and accounting for bias in whole-genome data sets supports the Ctenophora as sister to remaining Metazoa. BMC Genom. 16, 987. 8. Whelan, N.V., Kocot, K.M., Moroz, L.L., and Halanych, K.M. (2015). Error, signal, and the placement of Ctenophora sister to all other animals. Proc. Natl. Acad. Sci. USA 112, 5773–5778. 9. Philippe, H., Brinkmann, H., Lavrov, D.V., Littlewood, D.T., Manuel, M., Worheide, G., and Baurain, D. (2011). Resolving difficult phylogenetic questions: why more sequences are not enough. PLoS Biol. 9, e1000602.
10. Yang, Z., and Rannala, B. (2012). Molecular phylogenetics: principles and practice. Nat. Rev. Genet. 13, 303–314. 11. Lartillot, N., and Philippe, H. (2008). Improvement of molecular phylogenetic inference and the phylogeny of Bilateria. Phil. Trans. R. Soc. B 363, 1463–1472. 12. Whelan, N.V., and Halanych, K.M. (2017). Who let the CAT out of the bag? Accurately dealing with substitutional heterogeneity in phylogenomic analyses. Syst. Biol. http://dx. doi.org/10.1093/sysbio/syw084. 13. Ludeman, D.A., Farrar, N., Riesgo, A., Paps, J., and Leys, S.P. (2014). Evolutionary origins of sensation in metazoans: functional evidence for a new sensory organ in sponges. BMC Evol. Biol. 14, 3. 14. Presnell, J.S., Vandepas, L.E., Warren, K.J., Swalla, B.J., Amemiya, C.T., and Browne, W.E. (2016). The presence of a functionally tripartite through- gut in Ctenophora has implications for metazoan character trait evolution. Curr. Biol. 26, 2814–2820. 15. Ryan, J.F. (2016). Did the ctenophore nervous system evolve independently? Zoology 117, 225–226.
Sensorimotor Neuroscience: Motor Precision Meets Vision Kit D. Longden, Stephen J. Huston, and Michael B. Reiser* Janelia Research Campus19700, Helix Drive, Ashburn, VA 20147, USA *Correspondence: [email protected] http://dx.doi.org/10.1016/j.cub.2017.02.047
Visual motion sensing neurons in the fly also encode a range of behavior-related signals. These nonvisual inputs appear to be used to correct some of the challenges of visually guided locomotion.
The ability to pivot on the spot and change your direction is a useful skill, and not just for a politician. To do so our motor systems edit our visual responses, augmenting and adjusting our reality. This motor creation of sensory news happens in many and sophisticated ways, some of which are well known, and some have only recently been discovered [1,2]. At the most basic level, we structure our movements to suit our visual systems — witness a dancer ‘spotting’ a pirouette to minimize the time spent experiencing visual blur [3]. At the neural level, motor control centers conveniently silence our visual perception during rapid eye-
movements — saccades — when the world is also blurred, such that we never see the blur [4]. Recent data from mice and flies indicate that visual processing is also widely affected by locomotion, such that neurons serving many visual circuits encode not only visual motion, but also self-motion velocity, even in the dark [2,5]. Two new studies [6,7] indicate that flies pack all this motor modulation of visual processing into one visual pathway. For those of us studying sensory systems, this is something of a revelation — the motor activity occurs in benchmark cells for understanding efficient coding of
sensory information [8]. For those with a motor bent, the discoveries echo many of the principles operating in statedependent reflexes and their disengagement in voluntary actions, in cells with proposed roles in visual course control and object detection [9,10]. To dig into these stories, we need to meet the protagonists, the fly’s horizontal system (HS) and vertical system (VS) cells. The fly’s HS and VS cells are found in a visual brain area, the lobula plate (Figure 1A). They are exquisitely accessible for physiological recordings, and many decades of study have led to a
Current Biology 27, R259–R281, April 3, 2017 ª 2017 Elsevier Ltd. R261
Current Biology
Dispatches A
B
Central brain
Walking turn
Octopaminergic projection neuron
Visual motion
Visual motion inputs Extraretinal inputs
VS cell Optic lobe
HS cell
HS
Ascending Descending interneuron interneuron
C1 Flying saccade
C2 Visual motion
C3
Head saccade
Gazestabilizing reflex
Visual motion inputs
Head saccade
Gazestabilizing reflex
SRP
Roll
Visual motion inputs SRP
VS
Yaw
HS Current Biology
Figure 1. Behavioral signals influence the responses of fly visual neurons. (A) A population of visual neurons called HS (single example neuron shown in orange) and VS (green) cells respond to the visual motion that a fly sees when it turns relative to the world. The silhouette of the fly brain is shown in black, with visual neurons projecting from the optic lobe to the central brain. The VS and HS neurons synapse onto motor neurons (not shown) and descending neurons (red) that convey visual information to the thorax where the motor centers for flight and walking reside. This circuit can be modulated at many points, including potentially by octopaminergic neurons (turquoise) and ascending neurons (blue) providing feedback from the thorax. (Example neurons traced from images of stochastically labelled single neurons courtesy of Aljoscha Nern [20]). (B) When a walking fly turns to the left the image of the world moves to the right across its retina. The HS cell on the right side of the brain responds to the resulting visual motion. Fujiwara et al. [6] found that in addition to these cells receiving a visual signal indicating a leftward turn, they also receive a matching non-visual signal during leftward turns (triangles, excitation; circles, inhibition). This novel input ensures that the neuron responds to turns even under conditions where the visual system is unreliable, such as during rapid turns or in the dark. (C) Flying flies perform saccadic banked turns (C1), which contain both roll (C2, rotating about the body’s long axis) and yaw (C3, rotating about the vertical axis) components. When the fly rotates a gaze-stabilizing reflex normally drives the head to follow the direction of the resulting visual motion. HS cells are part of this reflex arc for yaw rotations and VS cells contribute to the same reflex for roll rotations [7,12,13]. During a saccadic turn, the roll component of this gaze stabilization reflex keeps the head level (C2), but the yaw component would interfere by preventing the head aligning with the turning direction (C3). Kim et al. [7] found that the more a neuron is responsive to yaw rotations, the more it is inhibited by an extra-retinal ‘saccade related potential’ (SRP) during a turn. The roll-responsive VS cells are only weakly affected by the SRP during the turn (C2) but the yawresponsive HS cells are strongly silenced (C3). Kim et al. [7] suggest that this ensures the counterproductive yaw gaze-stabilization reflex is transiently ‘turned-off’ during a turn but the useful roll reflex remains intact.
detailed understanding of their physiology and anatomy, and how these properties may contribute to behavior. Crucially, they are individually tuned to rotations of the fly along different body axes [11], a property that is thought to be used in at least two ways. First, they play a role in visual steering: they synapse with cells in the central brain and descending to the motor systems of the thorax [12], and lesioning these connections or the cells themselves reduces the stability of flight control [9]. Second, they also connect directly with neck motor neurons used in gaze-stabilizing head movements [12,13]. So while it has long been known that these cells are premotor neurons for the neck, it
has often been tacitly assumed that their main role is to provide visual motion information. In recent years, several findings have challenged this view. First, the HS and VS cells become more sensitive when the fly walks or flies [1,2], boosting visual responses. Second, the strength of the enhancement in the cells’ responses is correlated with walking speed [2]. Finally, the HS cells are inhibited during flight, when the fly makes rapid turns, also known as ‘saccades’ [14]. These observations have now been updated with detailed studies that demonstrate the precision and specificity with which the behavioral
R262 Current Biology 27, R259–R281, April 3, 2017
state and motor actions affect the HS and VS cells [6,7]. Fujiwara et al. [6] recorded the activity of HS cells while the fly walked on an air-supported ball, and discovered that the cells’ responses were simultaneously modulated by several components of the animal’s locomotion — the most striking was a strong effect of the turning direction (Figure 1B). These non-visual, or extraretinal, signals persisted even when vision and other sensory systems were physically or genetically silenced, suggesting that they were internally generated. Remarkably, the direction of turning that excited a given cell complemented the direction of visual motion to which the cell was tuned. That is, rightward turns and leftward visual motion (typically seen during a rightward turn) both excited the same neuron. As a result, the HS cells encode the turning of the fly, even without visual input. The effect of turning on the HS cell activity occurred with a delay of 100 milliseconds, which is within the timescale of an HS cell’s response to a visual turn [15]. To identify the effect of exciting HS cells, Fujiwara et al. [6] genetically expressed ATP-gated ion channels in them: activating the cells on one side of the brain induced walking turns. To synthesize these results requires speculation and further study: one tantalizing possibility is that the motor signal to the HS cell augments, with a suitable delay, a corrective steering response that follows when an HS cell is excited. These extraretinal signals were identified as common features across the fly’s rich repertoire of walking modes, but it is quite possible that different kinds of turns require alternative control strategies and sensorimotor regulation. Kim et al. [7] investigated how the activity of HS and VS cells is altered during flight saccades, and found an additional level of sophistication in how turning modulates their activity. They recorded the cells in tethered flight — a serendipitous configuration in which flies sustain somewhat naturalistic flight behavior (Figure 1C1). In a flight saccade, the body rotates with a mixture of roll and yaw rotations to achieve a banked turn [16]. As the body rolls, the head counter-rolls to keep the eyes level, and as the body yaws, the head turns sideways
Current Biology
Dispatches faster than the body, minimizing the period of visual blur, much like the dancer ‘spotting’ a turn [17]. Around the roll axis the head is moving in the opposite direction to the body to stabilize gaze, and around the yaw axis the head is moving in the same direction as the body. The first component is well explained by the roll gaze-stabilization reflex in which the VS cells are thought to participate (Figure 1C2). However, the yaw gaze-stabilization reflex, likely mediated by the HS cells, should counteract the second component (Figure 1C3): some mechanism is required to temporarily release the head from its yaw-stabilization. In contrast to the cooperative turning signal seen during walking [6], HS cells are inhibited during saccades in the direction that drive their visual input [14]. This ‘saccade related potential’ is well placed to effectively countermand the gaze-stabilization reflex during the turn. But are these signals simply silencing all of the HS and VS cells or was the effect more targeted? To address this question, Kim et al. [7] recorded from the entire population of HS and VS cells, which are tuned to distinct rotations. Remarkably, the more a cell was tuned to the rotational yaw component, the more its visual response was silenced during a turn [7]. The saccade signals were exquisitely tuned, arriving at the correct cells with the timing and strength to cancel only motion around the correct axis of rotation and leave other visual motion signals intact. Kim et al. [7] argue that this is precisely what is required during a saccade: to specifically damp down only the undesirable gazestabilizing head movements during a turn. One note of caution is in order: remember that these neurons contribute to controlling head movements [7]. At present, in vivo physiology in behaving flies is only practical in head-fixed animals, a situation that hinders the study of a head-movement regulating system. For example, the onset of saccades is reasonably preserved in these pseudo-flying flies, but their time course is dramatically altered by the absence of appropriate sensory feedback [18]. These studies provide an exciting opportunity to understand the
interconnected control systems for course control and gaze stabilization. A key step to synthesizing the results will be to identify how and where the behaviorrelated and visual signals are integrated. One likely source is projections from the central brain to the optic lobes. When the primary visual motion inputs to the HS cells were silenced using genetic methods, a nonspecific ‘arousal’-like depolarizing signal was eliminated, indicating it is presynaptic to the HS and VS cells [6]. Intriguingly, the axon terminals of HS and VS cells contain many pre-synaptic and post-synaptic sites [19], and are surrounded by the processes of interneurons descending to and ascending from the ventral nervous system [12], so the cells may be directly modulated by descending motor commands or ascending sensory or motor feedback. Now is the golden age of Drosophila neuroanatomy, ushered in by a combination of a much-improved genetic toolkit, advances in light microscopy, and connectomic reconstructions from electron microscopy data. Brain regions that were once too complex to be exhaustively studied at the level of identified neurons can now have their cells and circuitry catalogued [20]. Identifying the neurons conveying these motor-related signals and examining their functional properties will go a long way towards elucidating the dialogue between the so-called sensory systems and the motor-control centers during ongoing behavior. REFERENCES 1. Maimon, G., Straw, A.D., and Dickinson, M.H. (2010). Enhanced responses of visual neurons in flying Drosophila. Nat. Neurosci. 13, 393–399. 2. Chiappe, M.E., Seelig, J.D., Reiser, M.B., and Jayaraman, V. (2010). Walking modulates speed sensitivity in Drosophila motion vision. Curr. Biol. 20, 1470–1475. 3. Land, M.F. (2015). Eye movements of vertebrates and their relation to eye form and function. J. Comp. Physiol. A 201, 195–214. 4. Crapse, T.B., and Sommer, M.A. (2008). Corollary discharge circuits in the primate brain. Curr. Opin. Neurobiol. 18, 552–557. 5. Saleem, A.B., Ayaz, A., Jeffery, K.J., Harris, K.D., and Carandini, M. (2013). Integration of visual motion and locomotion in mouse visual cortex. Nat. Neurosci. 16, 1864–1869.
6. Fujiwara, T., Cruz, T.L., Bohnslav, J.P., and Chiappe, M.E. (2017). A faithful internal representation of walking movements in the Drosophila visual system. Nat. Neurosci. 20, 72–81. 7. Kim, A.J., Fenk, L.M., Lyu, C., and Maimon, G. (2017). Quantitative predictions orchestrate visual signaling in Drosophila. Cell 168, 280– 294.e12. 8. Harris, R.A., O’Carroll, D.C., and Laughlin, S.B. (2000). Contrast gain reduction in fly motion adaptation. Neuron 28, 595–606. 9. Hausen, K., and Wehrhahn, C. (1990). Neural circuits mediating visual flight control in flies. II. Separation of two control systems by microsurgical brain lesions. J. Neurosci. 10, 351–360. 10. Haikala, V., Joesch, M., Borst, A., and Mauss, A.S. (2013). Optogenetic control of fly optomotor responses. J. Neurosci. 33, 13927– 13934. 11. Krapp, H.G., Hengstenberg, R., and Egelhaaf, M. (2001). Binocular contributions to optic flow processing in the fly visual system. J. Neurophysiol. 85, 724–734. 12. Strausfeld, N.J., and Bassemir, U.K. (1985). Lobula plate and ocellar interneurons converge onto a cluster of descending neurons leading to neck and leg motor neuropil in Calliphora erythrocephala. Cell Tissue Res. 240, 617–640. 13. Huston, S.J., and Krapp, H.G. (2008). Visuomotor transformation in the fly gaze stabilization system. PLoS Biol. 6, 1468–1478. 14. Kim, A.J., Fitzgerald, J.K., and Maimon, G. (2015). Cellular evidence for efference copy in Drosophila visuomotor processing. Nat. Neurosci. 18, 1247–1255. 15. Schnell, B., Weir, P.T., Roth, E., Fairhall, A.L., and Dickinson, M.H. (2014). Cellular mechanisms for integral feedback in visually guided behavior. Proc. Natl. Acad. Sci. USA 111, 5700–5705. 16. Muijres, F.T., Elzinga, M.J., Iwasaki, N.A., and Dickinson, M.H. (2015). Body saccades of Drosophila consist of stereotyped banked turns. J. Exp. Biol. 218, 864–875. 17. van Hateren, J.H., and Schilstra, C. (1999). Blowfly flight and optic flow. II. Head movements during flight. J. Exp. Biol. 202, 1481–1490. 18. Bender, J.A., and Dickinson, M.H. (2006). A comparison of visual and haltere-mediated feedback in the control of body saccades in Drosophila melanogaster. J. Exp. Biol. 209, 4597–4606. 19. Pierantoni, R. (1976). A look into the cock-pit of the fly - The architecture of the lobular plate. Cell Tissue Res. 171, 101–122. 20. Nern, A., Pfeiffer, B.D., and Rubin, G.M. (2015). Optimized tools for multicolor stochastic labeling reveal diverse stereotyped cell arrangements in the fly visual system. Proc. Natl. Acad. Sci. USA 112, E2967– E2976.
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Dispatches be tested. Currently, our best estimate with the best data, and arguably the best tools, tells us sponges are the sister group to all other metazoans — we think. REFERENCES 1. Simion, P., Philippe, H., Baurain, D., Jager, M., Richter, D.J., Di Franco, A., Roure, B., Satoh, innec, E., Ereskovsky, A., et al. (2017). N., Que A large and consistent phylogenomic dataset supports sponges as the sister group to all other animals. Curr. Biol. 27, 958–967. 2. Telford, M.J., Budd, G.E., and Philippe, H. (2015). Phylogenomic insights into animal evolution. Curr. Biol. 25, R876–R887. 3. Leys, S.P., Nichols, S.A., and Adams, E.D. (2009). Epithelia and integration in sponges. Integr. Comp. Biol. 49, 167–177. 4. Dunn, C.W., Hejnol, A., Matus, D.Q., Pang, K., Browne, W.E., Smith, S.A., Seaver, E., Rouse, G.W., Obst, M., Edgecombe, G.D., et al. (2008). Broad phylogenomic sampling improves resolution of the animal tree of life. Nature 452, 745–749.
5. Philippe, H., Derelle, R., Lopez, P., Pick, K., Borchiellini, C., Boury-Esnault, N., Vacelet, J., innec, E., et al. Renard, E., Houliston, E., Que (2009). Phylogenomics revives traditional views on deep animal relationships. Curr. Biol. 19, 706–712. 6. Pisani, D., Pett, W., Dohrmann, M., Feuda, R., Rota-Stabelli, O., Philippe, H., Lartillot, N., and Wo¨rheide, G. (2015). Genomic data do not support comb jellies as the sister group to all other animals. Proc. Natl. Acad. Sci. USA 112, 15402–15407. 7. Borowiec, M.L., Lee, E.K., Chiu, J.C., and Plachetzki, D.C. (2015). Extracting phylogenetic signal and accounting for bias in whole-genome data sets supports the Ctenophora as sister to remaining Metazoa. BMC Genom. 16, 987. 8. Whelan, N.V., Kocot, K.M., Moroz, L.L., and Halanych, K.M. (2015). Error, signal, and the placement of Ctenophora sister to all other animals. Proc. Natl. Acad. Sci. USA 112, 5773–5778. 9. Philippe, H., Brinkmann, H., Lavrov, D.V., Littlewood, D.T., Manuel, M., Worheide, G., and Baurain, D. (2011). Resolving difficult phylogenetic questions: why more sequences are not enough. PLoS Biol. 9, e1000602.
10. Yang, Z., and Rannala, B. (2012). Molecular phylogenetics: principles and practice. Nat. Rev. Genet. 13, 303–314. 11. Lartillot, N., and Philippe, H. (2008). Improvement of molecular phylogenetic inference and the phylogeny of Bilateria. Phil. Trans. R. Soc. B 363, 1463–1472. 12. Whelan, N.V., and Halanych, K.M. (2017). Who let the CAT out of the bag? Accurately dealing with substitutional heterogeneity in phylogenomic analyses. Syst. Biol. http://dx. doi.org/10.1093/sysbio/syw084. 13. Ludeman, D.A., Farrar, N., Riesgo, A., Paps, J., and Leys, S.P. (2014). Evolutionary origins of sensation in metazoans: functional evidence for a new sensory organ in sponges. BMC Evol. Biol. 14, 3. 14. Presnell, J.S., Vandepas, L.E., Warren, K.J., Swalla, B.J., Amemiya, C.T., and Browne, W.E. (2016). The presence of a functionally tripartite through- gut in Ctenophora has implications for metazoan character trait evolution. Curr. Biol. 26, 2814–2820. 15. Ryan, J.F. (2016). Did the ctenophore nervous system evolve independently? Zoology 117, 225–226.
Sensorimotor Neuroscience: Motor Precision Meets Vision Kit D. Longden, Stephen J. Huston, and Michael B. Reiser* Janelia Research Campus19700, Helix Drive, Ashburn, VA 20147, USA *Correspondence: [email protected] http://dx.doi.org/10.1016/j.cub.2017.02.047
Visual motion sensing neurons in the fly also encode a range of behavior-related signals. These nonvisual inputs appear to be used to correct some of the challenges of visually guided locomotion.
The ability to pivot on the spot and change your direction is a useful skill, and not just for a politician. To do so our motor systems edit our visual responses, augmenting and adjusting our reality. This motor creation of sensory news happens in many and sophisticated ways, some of which are well known, and some have only recently been discovered [1,2]. At the most basic level, we structure our movements to suit our visual systems — witness a dancer ‘spotting’ a pirouette to minimize the time spent experiencing visual blur [3]. At the neural level, motor control centers conveniently silence our visual perception during rapid eye-
movements — saccades — when the world is also blurred, such that we never see the blur [4]. Recent data from mice and flies indicate that visual processing is also widely affected by locomotion, such that neurons serving many visual circuits encode not only visual motion, but also self-motion velocity, even in the dark [2,5]. Two new studies [6,7] indicate that flies pack all this motor modulation of visual processing into one visual pathway. For those of us studying sensory systems, this is something of a revelation — the motor activity occurs in benchmark cells for understanding efficient coding of
sensory information [8]. For those with a motor bent, the discoveries echo many of the principles operating in statedependent reflexes and their disengagement in voluntary actions, in cells with proposed roles in visual course control and object detection [9,10]. To dig into these stories, we need to meet the protagonists, the fly’s horizontal system (HS) and vertical system (VS) cells. The fly’s HS and VS cells are found in a visual brain area, the lobula plate (Figure 1A). They are exquisitely accessible for physiological recordings, and many decades of study have led to a
Current Biology 27, R259–R281, April 3, 2017 ª 2017 Elsevier Ltd. R261
Current Biology
Dispatches A
B
Central brain
Walking turn
Octopaminergic projection neuron
Visual motion
Visual motion inputs Extraretinal inputs
VS cell Optic lobe
HS cell
HS
Ascending Descending interneuron interneuron
C1 Flying saccade
C2 Visual motion
C3
Head saccade
Gazestabilizing reflex
Visual motion inputs
Head saccade
Gazestabilizing reflex
SRP
Roll
Visual motion inputs SRP
VS
Yaw
HS Current Biology
Figure 1. Behavioral signals influence the responses of fly visual neurons. (A) A population of visual neurons called HS (single example neuron shown in orange) and VS (green) cells respond to the visual motion that a fly sees when it turns relative to the world. The silhouette of the fly brain is shown in black, with visual neurons projecting from the optic lobe to the central brain. The VS and HS neurons synapse onto motor neurons (not shown) and descending neurons (red) that convey visual information to the thorax where the motor centers for flight and walking reside. This circuit can be modulated at many points, including potentially by octopaminergic neurons (turquoise) and ascending neurons (blue) providing feedback from the thorax. (Example neurons traced from images of stochastically labelled single neurons courtesy of Aljoscha Nern [20]). (B) When a walking fly turns to the left the image of the world moves to the right across its retina. The HS cell on the right side of the brain responds to the resulting visual motion. Fujiwara et al. [6] found that in addition to these cells receiving a visual signal indicating a leftward turn, they also receive a matching non-visual signal during leftward turns (triangles, excitation; circles, inhibition). This novel input ensures that the neuron responds to turns even under conditions where the visual system is unreliable, such as during rapid turns or in the dark. (C) Flying flies perform saccadic banked turns (C1), which contain both roll (C2, rotating about the body’s long axis) and yaw (C3, rotating about the vertical axis) components. When the fly rotates a gaze-stabilizing reflex normally drives the head to follow the direction of the resulting visual motion. HS cells are part of this reflex arc for yaw rotations and VS cells contribute to the same reflex for roll rotations [7,12,13]. During a saccadic turn, the roll component of this gaze stabilization reflex keeps the head level (C2), but the yaw component would interfere by preventing the head aligning with the turning direction (C3). Kim et al. [7] found that the more a neuron is responsive to yaw rotations, the more it is inhibited by an extra-retinal ‘saccade related potential’ (SRP) during a turn. The roll-responsive VS cells are only weakly affected by the SRP during the turn (C2) but the yawresponsive HS cells are strongly silenced (C3). Kim et al. [7] suggest that this ensures the counterproductive yaw gaze-stabilization reflex is transiently ‘turned-off’ during a turn but the useful roll reflex remains intact.
detailed understanding of their physiology and anatomy, and how these properties may contribute to behavior. Crucially, they are individually tuned to rotations of the fly along different body axes [11], a property that is thought to be used in at least two ways. First, they play a role in visual steering: they synapse with cells in the central brain and descending to the motor systems of the thorax [12], and lesioning these connections or the cells themselves reduces the stability of flight control [9]. Second, they also connect directly with neck motor neurons used in gaze-stabilizing head movements [12,13]. So while it has long been known that these cells are premotor neurons for the neck, it
has often been tacitly assumed that their main role is to provide visual motion information. In recent years, several findings have challenged this view. First, the HS and VS cells become more sensitive when the fly walks or flies [1,2], boosting visual responses. Second, the strength of the enhancement in the cells’ responses is correlated with walking speed [2]. Finally, the HS cells are inhibited during flight, when the fly makes rapid turns, also known as ‘saccades’ [14]. These observations have now been updated with detailed studies that demonstrate the precision and specificity with which the behavioral
R262 Current Biology 27, R259–R281, April 3, 2017
state and motor actions affect the HS and VS cells [6,7]. Fujiwara et al. [6] recorded the activity of HS cells while the fly walked on an air-supported ball, and discovered that the cells’ responses were simultaneously modulated by several components of the animal’s locomotion — the most striking was a strong effect of the turning direction (Figure 1B). These non-visual, or extraretinal, signals persisted even when vision and other sensory systems were physically or genetically silenced, suggesting that they were internally generated. Remarkably, the direction of turning that excited a given cell complemented the direction of visual motion to which the cell was tuned. That is, rightward turns and leftward visual motion (typically seen during a rightward turn) both excited the same neuron. As a result, the HS cells encode the turning of the fly, even without visual input. The effect of turning on the HS cell activity occurred with a delay of 100 milliseconds, which is within the timescale of an HS cell’s response to a visual turn [15]. To identify the effect of exciting HS cells, Fujiwara et al. [6] genetically expressed ATP-gated ion channels in them: activating the cells on one side of the brain induced walking turns. To synthesize these results requires speculation and further study: one tantalizing possibility is that the motor signal to the HS cell augments, with a suitable delay, a corrective steering response that follows when an HS cell is excited. These extraretinal signals were identified as common features across the fly’s rich repertoire of walking modes, but it is quite possible that different kinds of turns require alternative control strategies and sensorimotor regulation. Kim et al. [7] investigated how the activity of HS and VS cells is altered during flight saccades, and found an additional level of sophistication in how turning modulates their activity. They recorded the cells in tethered flight — a serendipitous configuration in which flies sustain somewhat naturalistic flight behavior (Figure 1C1). In a flight saccade, the body rotates with a mixture of roll and yaw rotations to achieve a banked turn [16]. As the body rolls, the head counter-rolls to keep the eyes level, and as the body yaws, the head turns sideways
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Dispatches faster than the body, minimizing the period of visual blur, much like the dancer ‘spotting’ a turn [17]. Around the roll axis the head is moving in the opposite direction to the body to stabilize gaze, and around the yaw axis the head is moving in the same direction as the body. The first component is well explained by the roll gaze-stabilization reflex in which the VS cells are thought to participate (Figure 1C2). However, the yaw gaze-stabilization reflex, likely mediated by the HS cells, should counteract the second component (Figure 1C3): some mechanism is required to temporarily release the head from its yaw-stabilization. In contrast to the cooperative turning signal seen during walking [6], HS cells are inhibited during saccades in the direction that drive their visual input [14]. This ‘saccade related potential’ is well placed to effectively countermand the gaze-stabilization reflex during the turn. But are these signals simply silencing all of the HS and VS cells or was the effect more targeted? To address this question, Kim et al. [7] recorded from the entire population of HS and VS cells, which are tuned to distinct rotations. Remarkably, the more a cell was tuned to the rotational yaw component, the more its visual response was silenced during a turn [7]. The saccade signals were exquisitely tuned, arriving at the correct cells with the timing and strength to cancel only motion around the correct axis of rotation and leave other visual motion signals intact. Kim et al. [7] argue that this is precisely what is required during a saccade: to specifically damp down only the undesirable gazestabilizing head movements during a turn. One note of caution is in order: remember that these neurons contribute to controlling head movements [7]. At present, in vivo physiology in behaving flies is only practical in head-fixed animals, a situation that hinders the study of a head-movement regulating system. For example, the onset of saccades is reasonably preserved in these pseudo-flying flies, but their time course is dramatically altered by the absence of appropriate sensory feedback [18]. These studies provide an exciting opportunity to understand the
interconnected control systems for course control and gaze stabilization. A key step to synthesizing the results will be to identify how and where the behaviorrelated and visual signals are integrated. One likely source is projections from the central brain to the optic lobes. When the primary visual motion inputs to the HS cells were silenced using genetic methods, a nonspecific ‘arousal’-like depolarizing signal was eliminated, indicating it is presynaptic to the HS and VS cells [6]. Intriguingly, the axon terminals of HS and VS cells contain many pre-synaptic and post-synaptic sites [19], and are surrounded by the processes of interneurons descending to and ascending from the ventral nervous system [12], so the cells may be directly modulated by descending motor commands or ascending sensory or motor feedback. Now is the golden age of Drosophila neuroanatomy, ushered in by a combination of a much-improved genetic toolkit, advances in light microscopy, and connectomic reconstructions from electron microscopy data. Brain regions that were once too complex to be exhaustively studied at the level of identified neurons can now have their cells and circuitry catalogued [20]. Identifying the neurons conveying these motor-related signals and examining their functional properties will go a long way towards elucidating the dialogue between the so-called sensory systems and the motor-control centers during ongoing behavior. REFERENCES 1. Maimon, G., Straw, A.D., and Dickinson, M.H. (2010). Enhanced responses of visual neurons in flying Drosophila. Nat. Neurosci. 13, 393–399. 2. Chiappe, M.E., Seelig, J.D., Reiser, M.B., and Jayaraman, V. (2010). Walking modulates speed sensitivity in Drosophila motion vision. Curr. Biol. 20, 1470–1475. 3. Land, M.F. (2015). Eye movements of vertebrates and their relation to eye form and function. J. Comp. Physiol. A 201, 195–214. 4. Crapse, T.B., and Sommer, M.A. (2008). Corollary discharge circuits in the primate brain. Curr. Opin. Neurobiol. 18, 552–557. 5. Saleem, A.B., Ayaz, A., Jeffery, K.J., Harris, K.D., and Carandini, M. (2013). Integration of visual motion and locomotion in mouse visual cortex. Nat. Neurosci. 16, 1864–1869.
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