- Email: [email protected]
IA in Play
Neuron
Previews Jordt, S.E., McKemy, D.D., and Julius, D. (2003). Curr. Opin. Neurobiol. 13, 487– 492.
McCleverty, C.J., Koesema, E., Patapoutian, A., Lesley, S.A., and Kreusch, A. (2006). Protein Sci. 15, 2201–2206. Prescott, E.D., and Julius, D. (2003). Science 300, 1284–1288.
Clapham, D.E. (2003). Nature 426, 517–524.
Kwak, J., Wang, M.H., Hwang, S.W., Kim, T.Y., Lee, S.Y., and Oh, U. (2000). J. Neurosci. 20, 8298–8304.
Hardie, R.C., Raghu, P., Moore, S., Juusola, M., Baines, R.A., and Sweeney, S.T. (2001). Neuron 30, 149–159.
Lishko, P.V., Procko, E., Jin, X., Phelps, C.B., and Gaudet, R. (2007). Neuron 54, this issue, 905–918.
Hinman, A., Chuang, H.H., Bautista, D.M., and Julius, D. (2006). Proc. Natl. Acad. Sci. USA 103, 19564–19568.
Liu, B., Zhang, C., and Qin, F. (2005). J. Neurosci. 25, 4835–4843.
REFERENCES Chuang, H.H., Prescott, E.D., Kong, H., Shields, S., Jordt, S.E., Basbaum, A.I., Chao, M.V., and Julius, D. (2001). Nature 411, 957–962.
Jin, X., Touhey, J., and Gaudet, R. (2006). J. Biol. Chem. 281, 25006–25010.
Macpherson, L.J., Dubin, A.E., Evans, M.J., Marr, F., Schultz, P.G., Cravatt, B.F., and Patapoutian, A. (2007). Nature 445, 541–545.
Stein, A.T., Ufret-Vincenty, C.A., Hua, L., Santana, L.F., and Gordon, S.E. (2006). J. Gen. Physiol. 128, 509–522. Tominaga, M., and Tominaga, T. (2005). Pflugers Arch. 451, 143–150. Tominaga, M., Caterina, M.J., Malmberg, A.B., Rosen, T.A., Gilbert, H., Skinner, K., Raumann, B.E., Basbaum, A.I., and Julius, D. (1998). Neuron 21, 531–543.
IA in Play Scott M. Thompson1,* 1
Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA *Correspondence: [email protected] DOI 10.1016/j.neuron.2007.06.008
Everyone agrees about how long-term potentiation (LTP) is induced—NMDA receptor activation— but much remains to be learned about how the increase in the strength of a synaptic connection between two neurons is expressed. In this issue of Neuron, Kim et al. report a new form of NMDAR-dependent plasticity that may contribute to LTP: internalization of postsynaptic Kv4.2 potassium channels that mediate transient IA-type outward current in dendrites.
An increase in the strength of the excitatory connections between principal neurons is the predominant means by which an engram is stored during the learning process. It is widely accepted that synaptic strength is increased when strong, temporally correlated presynaptic activity produces both glutamate release and a sufficiently large depolarization of the postsynaptic cell’s membrane potential to relieve the block of the NMDA-type glutamate receptor (NMDAR) by Mg2+ ions. Ca2+ ions thereby enter the postsynaptic dendritic spine, and the resulting elevation of the free intracellular Ca2+ concentration triggers a cascade of enzymatic pathways that ultimately results in the strengthening of the synapse. The nature of the change (or changes) in the connection between the two cells that is responsible for
the increase in synaptic strength remains highly contentious. There is now overwhelming evidence that an increase in the number of AMPA-type glutamate receptors in the postsynaptic plasma membrane is induced in long-term potentiation (LTP) of excitatory synaptic transmission, a heavily studied form of NMDAR-dependent synaptic plasticity (Malenka and Bear, 2004). The increase in receptor number results in a larger depolarization of the postsynaptic cell in response to a given amount of presynaptic glutamate release. There is also evidence that factors ‘‘downstream’’ of direct synaptic modulation also contribute to the overall increase in the strength of a synaptic connection during learning, such as changes in the intrinsic ionic currents of the postsynaptic cell. In this issue of Neuron,
850 Neuron 54, June 21, 2007 ª2007 Elsevier Inc.
Kim et al. (2007) report an exciting new form of NMDAR-dependent plasticity and suggest that this process contributes to synaptic potentiation: internalization of transient A-type outward current mediated by Kv4.2 potassium channels. The dendrites of pyramidal cells are endowed with a variety of voltagedependent channels that sculpt the voltage changes induced in the postsynaptic cell in response to synaptic activation. One particularly important dendritic current is the A-type potassium current (IA). This outward current is activated by even small depolarizations from the cell’s normal resting membrane potential. It has the biophysical characteristic of strong inactivation. That is, it activates rapidly in response to depolarization, but the channels stop passing current within
Neuron
Previews a few 10s of milliseconds, even when the depolarization is maintained. IA is thus a form of transient outward current. IA is activated by small EPSPs and has been shown to limit their amplitude and accelerate the time course of their decay (Hoffman et al., 1997). IA also limits the backward propagation of action potentials generated at the soma into the dendritic tree (Hoffman et al., 1997) and, at branch points, the forward propagation of depolarization out of the dendritic branch in which the excitatory synapse is located (Cai et al., 2004). Interestingly, the amount of IA in a given dendrite increases with distance from the cell body (Hoffman et al., 1997). Multiple channel types can mediate A-type transient outward current, and recent evidence has established that channels encoded by the Kv4.2 gene form the majority of the dendritic IA (Cai et al., 2004; Chen et al., 2006). What Kim et al. have discovered is that the number of Kv4.2 channels in the plasma membrane of the dendritic spine is reduced rapidly in response to NMDAR activation. They expressed a GFP-tagged Kv4.2 construct in cultured hippocampal neurons and observed a strong preferential localization of the channels in dendritic spines, a finding corroborated by immunogold labeling of native Kv4.2 channels in adult rat hippocampal tissue prepared for electron microscopy. In response to transient stimulation of NMDARs, Kim et al. observed that dendritic spines lost significant amounts of GFP emission, starting immediately upon stimulation and continuing for at least 15 min. Other pre- and postsynaptic markers were unaffected, however, indicating that the effect was specific for the Kv4.2 channels. In the absence of further stimulation, recovery of fluorescence took 6 hr. Labeling of Kv4.2 channels at the cell surface with a biotinylated antibody revealed that NMDAR activation resulted in the translocation of the channels from the cell surface to intracellular compartments. The identity of these compartments, and hence the fate of the internalized channels, remains to be determined. Similar results were obtained in ex vivo hippo-
Figure 1.
campal slices. If the channels are no longer present in the plasma membrane, then a reduction in IA can be predicted. Indeed, whole-cell voltage-clamp recording of potassium currents demonstrated that there was a decrease in transient outward current, whereas noninactivating outward currents were unaffected. The authors go on to show that internalization of Kv4.2 channels in response to NMDAR activation is mediated by a clathrin-dependent process. When cells were loaded with a peptide fragment of the protein dynamin, which competes with the endogenous dynamin and thereby prevents dynamin- and clathrin-dependent endocytosis, both the loss of Kv4.2-GFP fluorescence and the decrease in IA induced by glutamatergic stimulation were eliminated. Because the conditions used to induce Kv4.2 internalization resembled those used to induce LTP, the authors hypothesized that Kv4.2 internalization contributes to the expression of LTP. They first demonstrated that the level of Kv4.2 expression affects the amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in a voltage-dependent manner consistent with the properties of the channels. That is, at membrane potentials more negative than the resting potential, the channels are closed, and the
overexpression of Kv4.2 channels or the expression of a dominant-negative channel has no effect on mEPSC amplitude. At membrane potentials just depolarized to the resting potential, in contrast, mEPSC amplitude is inversely related to the amount of IA. Dominant-negative Kv4.2 channels reduce IA and increase mEPSC amplitude, whereas overexpression of Kv4.2 increases IA and reduces mEPSC amplitude. Using cultured hippocampal slices, the authors then demonstrate that induction of LTP results in a greater increase in EPSC amplitude when responses are elicited at 60 mV than at 80 mV. Because IA attenuates EPSCs at 60 mV, they suggest that the ‘‘extra’’ potentiation at 60 mV is the result of internalization of Kv4.2 channels and the resulting decrease in IA. In summary, Kim et al. propose a model (see Figure 1) in which strong correlated excitatory synaptic activity leads to NMDAR activation, which then induces within minutes a clathrin-mediated endocytosis of Kv4.2 channels from the dendritic spine. As a result of this loss of plasma membrane Kv4.2 channels, IA is decreased in amplitude. The reduction in IA acts in synergy with the insertion of postsynaptic AMPARs to increase the potentiation of EPSPs at the resting potential or more depolarized potentials.
Neuron 54, June 21, 2007 ª2007 Elsevier Inc. 851
Neuron
Previews The evidence of Kv4.2 internalization in response to NMDAR activation as presented by the authors is clear, persuasive, and exciting. The contribution of this novel process to LTP is sure to excite additional work in order to iron out differences between the present study and previous work. For example, Frick et al. (2004) used oncell patch recording to study dendritic IA before and after LTP induction in ex vivo hippocampal slices. They reported that the voltage dependence of channel inactivation was altered slightly, reducing channel availability, but they did not report any evidence consistent with internalization. Clathrin-mediated endocytosis is thought to underlie internalization of AMPARs in long-term depression (Man et al., 2000). It will be a challenge to determine how the cell sorts its plasma membrane proteins after LTP induction so that Kv4.2 channels are internalized, but not AMPARs. Finally, it will be interesting to determine whether depotentiation restores IA and spine Kv4.2 channels. If not, then the authors’ hypothesis makes a clear
prediction that depotentiation should be greater at 80 mV than at 60 mV. There is nothing like an exciting result and a good controversy to send the LTP crowd rushing to their rigs! An often neglected finding is that strong correlated activity not only potentiates excitatory synaptic transmission itself, but it also results in a potentiation of the ability of a given amount of synaptic excitation to induce action potentials in the postsynaptic cell (Andersen et al., 1980). Like the synaptic component of LTP, this phenomenon, known as potentiation of excitation-spike coupling, is NMDAR dependent, input specific, and bidirectional (Daoudal et al., 2002). The internalization of Kv4.2 and decrease in IA described by Kim et al. would seem to be consistent with descriptions of changes in EPSPs after LTP (Abraham et al., 1987) and therefore offers an attractive explanation for potentiation of excitation-spike coupling. Kim et al. have shown us that IA is in play—let the follow-up experiments begin!
REFERENCES Abraham, W., Gustafsson, B., and Wigstrom, H. (1987). J. Physiol. 394, 367–380. Andersen, P., Sundberg, S.H., Sveen, O., Swann, J.W., and Wigstro¨m, H. (1980). J. Physiol. 302, 463–482. Cai, X., Liang, C.W., Muralidharan, S., Kao, J.P., Tang, C.-M., and Thompson, S.M. (2004). Neuron 44, 351–364. Chen, X., Yuan, L.L., Zhao, C., Birnbaum, S.G., Frick, A., Jung, W.E., Schwarz, T.L., Sweatt, J.D., and Johnston, D. (2006). J. Neurosci. 26, 12143–12151. Daoudal, G., Hanada, Y., and Debanne, D. (2002). Proc. Natl. Acad. Sci. USA 99, 14512– 14517. Hoffman, D.A., Magee, J.C., Colbert, C.M., and Johnston, D. (1997). Nature 387, 869– 875. Frick, A., Magee, J., and Johnston, D. (2004). Nat. Neurosci. 7, 126–135. Kim, J., Jung, S.-C., Clemens, A.M., Petralia, R.S., and Hoffman, D.A. (2007). Neuron 54, this issue, 933–947. Malenka, R.C., and Bear, M.F. (2004). Neuron 44, 5–21. Man, H.Y., Lin, J.W., Ju, W.H., Ahmadian, G., Liu, L., Becker, L.E., Sheng, M., and Wang, Y.T. (2000). Neuron 25, 649– 662.
Finding Our Way around the Sensory-Motor Corner Richard J. Krauzlis1,* and Ziad M. Hafed1 1
Systems Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA *Correspondence: [email protected] DOI 10.1016/j.neuron.2007.06.012
Our understanding of how sensory information is transformed into motor commands has grown increasingly sophisticated. In this issue of Neuron, Wilmer and Nakayama use a novel analysis to show that the initial changes in smooth-pursuit eye speed are driven by low-level motion signals, whereas the later eye speed is determined by high-level signals.
Conventional wisdom once held that sensory-motor processing for saccadic and pursuit eye movements might be explained by a relatively straightforward pair of transformations. On the one hand, saccades involve transforming signals about the locations of stimuli into the bursts of
motor activity needed to quickly redirect the eyes toward these stimuli. On the other hand, pursuit eye movements are generated by a different set of transformations that convert signals about visual motion into the motor commands that smoothly rotate the eyes. Although these types of transfor-
852 Neuron 54, June 21, 2007 ª2007 Elsevier Inc.
mations are still viewed as fundamental steps in turning the sensory-motor corner for eye movements, the overall process is considerably more complicated (see Figure 1). The pursuit and saccadic systems do not operate independently, but instead they interact with each other and are also linked to
Previews Jordt, S.E., McKemy, D.D., and Julius, D. (2003). Curr. Opin. Neurobiol. 13, 487– 492.
McCleverty, C.J., Koesema, E., Patapoutian, A., Lesley, S.A., and Kreusch, A. (2006). Protein Sci. 15, 2201–2206. Prescott, E.D., and Julius, D. (2003). Science 300, 1284–1288.
Clapham, D.E. (2003). Nature 426, 517–524.
Kwak, J., Wang, M.H., Hwang, S.W., Kim, T.Y., Lee, S.Y., and Oh, U. (2000). J. Neurosci. 20, 8298–8304.
Hardie, R.C., Raghu, P., Moore, S., Juusola, M., Baines, R.A., and Sweeney, S.T. (2001). Neuron 30, 149–159.
Lishko, P.V., Procko, E., Jin, X., Phelps, C.B., and Gaudet, R. (2007). Neuron 54, this issue, 905–918.
Hinman, A., Chuang, H.H., Bautista, D.M., and Julius, D. (2006). Proc. Natl. Acad. Sci. USA 103, 19564–19568.
Liu, B., Zhang, C., and Qin, F. (2005). J. Neurosci. 25, 4835–4843.
REFERENCES Chuang, H.H., Prescott, E.D., Kong, H., Shields, S., Jordt, S.E., Basbaum, A.I., Chao, M.V., and Julius, D. (2001). Nature 411, 957–962.
Jin, X., Touhey, J., and Gaudet, R. (2006). J. Biol. Chem. 281, 25006–25010.
Macpherson, L.J., Dubin, A.E., Evans, M.J., Marr, F., Schultz, P.G., Cravatt, B.F., and Patapoutian, A. (2007). Nature 445, 541–545.
Stein, A.T., Ufret-Vincenty, C.A., Hua, L., Santana, L.F., and Gordon, S.E. (2006). J. Gen. Physiol. 128, 509–522. Tominaga, M., and Tominaga, T. (2005). Pflugers Arch. 451, 143–150. Tominaga, M., Caterina, M.J., Malmberg, A.B., Rosen, T.A., Gilbert, H., Skinner, K., Raumann, B.E., Basbaum, A.I., and Julius, D. (1998). Neuron 21, 531–543.
IA in Play Scott M. Thompson1,* 1
Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA *Correspondence: [email protected] DOI 10.1016/j.neuron.2007.06.008
Everyone agrees about how long-term potentiation (LTP) is induced—NMDA receptor activation— but much remains to be learned about how the increase in the strength of a synaptic connection between two neurons is expressed. In this issue of Neuron, Kim et al. report a new form of NMDAR-dependent plasticity that may contribute to LTP: internalization of postsynaptic Kv4.2 potassium channels that mediate transient IA-type outward current in dendrites.
An increase in the strength of the excitatory connections between principal neurons is the predominant means by which an engram is stored during the learning process. It is widely accepted that synaptic strength is increased when strong, temporally correlated presynaptic activity produces both glutamate release and a sufficiently large depolarization of the postsynaptic cell’s membrane potential to relieve the block of the NMDA-type glutamate receptor (NMDAR) by Mg2+ ions. Ca2+ ions thereby enter the postsynaptic dendritic spine, and the resulting elevation of the free intracellular Ca2+ concentration triggers a cascade of enzymatic pathways that ultimately results in the strengthening of the synapse. The nature of the change (or changes) in the connection between the two cells that is responsible for
the increase in synaptic strength remains highly contentious. There is now overwhelming evidence that an increase in the number of AMPA-type glutamate receptors in the postsynaptic plasma membrane is induced in long-term potentiation (LTP) of excitatory synaptic transmission, a heavily studied form of NMDAR-dependent synaptic plasticity (Malenka and Bear, 2004). The increase in receptor number results in a larger depolarization of the postsynaptic cell in response to a given amount of presynaptic glutamate release. There is also evidence that factors ‘‘downstream’’ of direct synaptic modulation also contribute to the overall increase in the strength of a synaptic connection during learning, such as changes in the intrinsic ionic currents of the postsynaptic cell. In this issue of Neuron,
850 Neuron 54, June 21, 2007 ª2007 Elsevier Inc.
Kim et al. (2007) report an exciting new form of NMDAR-dependent plasticity and suggest that this process contributes to synaptic potentiation: internalization of transient A-type outward current mediated by Kv4.2 potassium channels. The dendrites of pyramidal cells are endowed with a variety of voltagedependent channels that sculpt the voltage changes induced in the postsynaptic cell in response to synaptic activation. One particularly important dendritic current is the A-type potassium current (IA). This outward current is activated by even small depolarizations from the cell’s normal resting membrane potential. It has the biophysical characteristic of strong inactivation. That is, it activates rapidly in response to depolarization, but the channels stop passing current within
Neuron
Previews a few 10s of milliseconds, even when the depolarization is maintained. IA is thus a form of transient outward current. IA is activated by small EPSPs and has been shown to limit their amplitude and accelerate the time course of their decay (Hoffman et al., 1997). IA also limits the backward propagation of action potentials generated at the soma into the dendritic tree (Hoffman et al., 1997) and, at branch points, the forward propagation of depolarization out of the dendritic branch in which the excitatory synapse is located (Cai et al., 2004). Interestingly, the amount of IA in a given dendrite increases with distance from the cell body (Hoffman et al., 1997). Multiple channel types can mediate A-type transient outward current, and recent evidence has established that channels encoded by the Kv4.2 gene form the majority of the dendritic IA (Cai et al., 2004; Chen et al., 2006). What Kim et al. have discovered is that the number of Kv4.2 channels in the plasma membrane of the dendritic spine is reduced rapidly in response to NMDAR activation. They expressed a GFP-tagged Kv4.2 construct in cultured hippocampal neurons and observed a strong preferential localization of the channels in dendritic spines, a finding corroborated by immunogold labeling of native Kv4.2 channels in adult rat hippocampal tissue prepared for electron microscopy. In response to transient stimulation of NMDARs, Kim et al. observed that dendritic spines lost significant amounts of GFP emission, starting immediately upon stimulation and continuing for at least 15 min. Other pre- and postsynaptic markers were unaffected, however, indicating that the effect was specific for the Kv4.2 channels. In the absence of further stimulation, recovery of fluorescence took 6 hr. Labeling of Kv4.2 channels at the cell surface with a biotinylated antibody revealed that NMDAR activation resulted in the translocation of the channels from the cell surface to intracellular compartments. The identity of these compartments, and hence the fate of the internalized channels, remains to be determined. Similar results were obtained in ex vivo hippo-
Figure 1.
campal slices. If the channels are no longer present in the plasma membrane, then a reduction in IA can be predicted. Indeed, whole-cell voltage-clamp recording of potassium currents demonstrated that there was a decrease in transient outward current, whereas noninactivating outward currents were unaffected. The authors go on to show that internalization of Kv4.2 channels in response to NMDAR activation is mediated by a clathrin-dependent process. When cells were loaded with a peptide fragment of the protein dynamin, which competes with the endogenous dynamin and thereby prevents dynamin- and clathrin-dependent endocytosis, both the loss of Kv4.2-GFP fluorescence and the decrease in IA induced by glutamatergic stimulation were eliminated. Because the conditions used to induce Kv4.2 internalization resembled those used to induce LTP, the authors hypothesized that Kv4.2 internalization contributes to the expression of LTP. They first demonstrated that the level of Kv4.2 expression affects the amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in a voltage-dependent manner consistent with the properties of the channels. That is, at membrane potentials more negative than the resting potential, the channels are closed, and the
overexpression of Kv4.2 channels or the expression of a dominant-negative channel has no effect on mEPSC amplitude. At membrane potentials just depolarized to the resting potential, in contrast, mEPSC amplitude is inversely related to the amount of IA. Dominant-negative Kv4.2 channels reduce IA and increase mEPSC amplitude, whereas overexpression of Kv4.2 increases IA and reduces mEPSC amplitude. Using cultured hippocampal slices, the authors then demonstrate that induction of LTP results in a greater increase in EPSC amplitude when responses are elicited at 60 mV than at 80 mV. Because IA attenuates EPSCs at 60 mV, they suggest that the ‘‘extra’’ potentiation at 60 mV is the result of internalization of Kv4.2 channels and the resulting decrease in IA. In summary, Kim et al. propose a model (see Figure 1) in which strong correlated excitatory synaptic activity leads to NMDAR activation, which then induces within minutes a clathrin-mediated endocytosis of Kv4.2 channels from the dendritic spine. As a result of this loss of plasma membrane Kv4.2 channels, IA is decreased in amplitude. The reduction in IA acts in synergy with the insertion of postsynaptic AMPARs to increase the potentiation of EPSPs at the resting potential or more depolarized potentials.
Neuron 54, June 21, 2007 ª2007 Elsevier Inc. 851
Neuron
Previews The evidence of Kv4.2 internalization in response to NMDAR activation as presented by the authors is clear, persuasive, and exciting. The contribution of this novel process to LTP is sure to excite additional work in order to iron out differences between the present study and previous work. For example, Frick et al. (2004) used oncell patch recording to study dendritic IA before and after LTP induction in ex vivo hippocampal slices. They reported that the voltage dependence of channel inactivation was altered slightly, reducing channel availability, but they did not report any evidence consistent with internalization. Clathrin-mediated endocytosis is thought to underlie internalization of AMPARs in long-term depression (Man et al., 2000). It will be a challenge to determine how the cell sorts its plasma membrane proteins after LTP induction so that Kv4.2 channels are internalized, but not AMPARs. Finally, it will be interesting to determine whether depotentiation restores IA and spine Kv4.2 channels. If not, then the authors’ hypothesis makes a clear
prediction that depotentiation should be greater at 80 mV than at 60 mV. There is nothing like an exciting result and a good controversy to send the LTP crowd rushing to their rigs! An often neglected finding is that strong correlated activity not only potentiates excitatory synaptic transmission itself, but it also results in a potentiation of the ability of a given amount of synaptic excitation to induce action potentials in the postsynaptic cell (Andersen et al., 1980). Like the synaptic component of LTP, this phenomenon, known as potentiation of excitation-spike coupling, is NMDAR dependent, input specific, and bidirectional (Daoudal et al., 2002). The internalization of Kv4.2 and decrease in IA described by Kim et al. would seem to be consistent with descriptions of changes in EPSPs after LTP (Abraham et al., 1987) and therefore offers an attractive explanation for potentiation of excitation-spike coupling. Kim et al. have shown us that IA is in play—let the follow-up experiments begin!
REFERENCES Abraham, W., Gustafsson, B., and Wigstrom, H. (1987). J. Physiol. 394, 367–380. Andersen, P., Sundberg, S.H., Sveen, O., Swann, J.W., and Wigstro¨m, H. (1980). J. Physiol. 302, 463–482. Cai, X., Liang, C.W., Muralidharan, S., Kao, J.P., Tang, C.-M., and Thompson, S.M. (2004). Neuron 44, 351–364. Chen, X., Yuan, L.L., Zhao, C., Birnbaum, S.G., Frick, A., Jung, W.E., Schwarz, T.L., Sweatt, J.D., and Johnston, D. (2006). J. Neurosci. 26, 12143–12151. Daoudal, G., Hanada, Y., and Debanne, D. (2002). Proc. Natl. Acad. Sci. USA 99, 14512– 14517. Hoffman, D.A., Magee, J.C., Colbert, C.M., and Johnston, D. (1997). Nature 387, 869– 875. Frick, A., Magee, J., and Johnston, D. (2004). Nat. Neurosci. 7, 126–135. Kim, J., Jung, S.-C., Clemens, A.M., Petralia, R.S., and Hoffman, D.A. (2007). Neuron 54, this issue, 933–947. Malenka, R.C., and Bear, M.F. (2004). Neuron 44, 5–21. Man, H.Y., Lin, J.W., Ju, W.H., Ahmadian, G., Liu, L., Becker, L.E., Sheng, M., and Wang, Y.T. (2000). Neuron 25, 649– 662.
Finding Our Way around the Sensory-Motor Corner Richard J. Krauzlis1,* and Ziad M. Hafed1 1
Systems Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA *Correspondence: [email protected] DOI 10.1016/j.neuron.2007.06.012
Our understanding of how sensory information is transformed into motor commands has grown increasingly sophisticated. In this issue of Neuron, Wilmer and Nakayama use a novel analysis to show that the initial changes in smooth-pursuit eye speed are driven by low-level motion signals, whereas the later eye speed is determined by high-level signals.
Conventional wisdom once held that sensory-motor processing for saccadic and pursuit eye movements might be explained by a relatively straightforward pair of transformations. On the one hand, saccades involve transforming signals about the locations of stimuli into the bursts of
motor activity needed to quickly redirect the eyes toward these stimuli. On the other hand, pursuit eye movements are generated by a different set of transformations that convert signals about visual motion into the motor commands that smoothly rotate the eyes. Although these types of transfor-
852 Neuron 54, June 21, 2007 ª2007 Elsevier Inc.
mations are still viewed as fundamental steps in turning the sensory-motor corner for eye movements, the overall process is considerably more complicated (see Figure 1). The pursuit and saccadic systems do not operate independently, but instead they interact with each other and are also linked to