Maximilian Joesch | Harvard University (original) (raw)
Papers by Maximilian Joesch
In bright light, cone-photoreceptors are active and colour vision derives from a comparison of si... more In bright light, cone-photoreceptors are active and colour vision derives from a comparison of signals in cones with different visual pigments. This comparison begins in the retina, where certain retinal ganglion cells have 'colour-opponent' visual responses— excited by light of one colour and suppressed by another colour 1. In dim light, rod-photoreceptors are active, but colour vision is impossible because they all use the same visual pigment. Instead, the rod signals are thought to splice into retinal circuits at various points, in synergy with the cone signals 2. Here we report a new circuit for colour vision that challenges these expectations. A genetically identified type of mouse retinal ganglion cell called JAMB (J-RGC) 3 , was found to have colour-opponent responses, OFF to ultraviolet (UV) light and ON to green light. Although the mouse retina contains a green-sensitive cone, the ON response instead originates in rods. Rods and cones both contribute to the response over several decades of light intensity. Remarkably, the rod signal in this circuit is antagonistic to that from cones. For rodents, this UV-green channel may play a role in social communication, as suggested by spectral measurements from the environment. In the human retina, all of the components for this circuit exist as well, and its function can explain certain experiences of colour in dim lights, such as a 'blue shift' in twilight. The discovery of this genetically defined pathway will enable new targeted studies of colour processing in the brain. Like most mammals, the mouse has one type of rod and two types of cone photoreceptors, with absorption maxima in the ultraviolet (S pigment) and green (M pigment) region of the spectrum. As in other small mammals, the retinal organization of the cones is inhomogeneous: the M and S pigments are largely segregated in the dorsal and ventral retina, respectively 4. At the level of ganglion cells, the spectral sensitivity essentially follows this cone distribution 5,6 , which severely limits any local comparison of signals across cone pigments. Because behavioural experiments show that mice can indeed 'see colour' 7 , it has been suggested that colour vision in mice operates on very different principles from primates 8. Surprisingly, as we demonstrate here, the mouse does have a dedicated ganglion cell type with clearly opponent responses to light of different wavelengths. It uses an unexpected retinal circuit that circumvents the obstacle caused by the spatial segregation of cone pigments. We recorded the visual responses of J-RGCs in the retina of a mouse line that labels these neurons fluorescently 3 (Fig. 1a). When probed with white light, the receptive field has OFF-type sensitivity in the centre and ON-type sensitivity in the surround (Fig. 1b). As reported previously, the surround is stronger on the side of the asymmetric den-dritic arbor 3. Stimulation using coloured lights led to a surprise. Many J-RGCs produce an OFF response to uniform UV light,
Nature, 2016
In bright light, cone-photoreceptors are active and colour vision derives from a comparison of si... more In bright light, cone-photoreceptors are active and colour vision derives from a comparison of signals in cones with different visual pigments. This comparison begins in the retina, where certain retinal ganglion cells have 'colour-opponent' visual responses-excited by light of one colour and suppressed by another colour. In dim light, rod-photoreceptors are active, but colour vision is impossible because they all use the same visual pigment. Instead, the rod signals are thought to splice into retinal circuits at various points, in synergy with the cone signals. Here we report a new circuit for colour vision that challenges these expectations. A genetically identified type of mouse retinal ganglion cell called JAMB (J-RGC), was found to have colour-opponent responses, OFF to ultraviolet (UV) light and ON to green light. Although the mouse retina contains a green-sensitive cone, the ON response instead originates in rods. Rods and cones both contribute to the response over several decades of light intensity. Remarkably, the rod signal in this circuit is antagonistic to that from cones. For rodents, this UV-green channel may play a role in social communication, as suggested by spectral measurements from the environment. In the human retina, all of the components for this circuit exist as well, and its function can explain certain experiences of colour in dim lights, such as a 'blue shift' in twilight. The discovery of this genetically defined pathway will enable new targeted studies of colour processing in the brain.
Journal of Neuroscience, 2013
In the fly Drosophila melanogaster, photoreceptor input to motion vision is split into two parall... more In the fly Drosophila melanogaster, photoreceptor input to motion vision is split into two parallel pathways as represented by first-order interneurons L1 and L2 (Rister et al., 2007; Joesch et al., 2010). However, how these pathways are functionally specialized remains controversial. One study (Eichner et al., 2011) proposed that the L1-pathway evaluates only sequences of brightness increments (ON-ON), while the L2-pathway processes exclusively brightness decrements (OFF-OFF). Another study (Clark et al., 2011) proposed that each of the two pathways evaluates both ON-ON and OFF-OFF sequences.
Journal of Neuroscience, 2013
When confronted with a large-field stimulus rotating around the vertical body axis, flies display... more When confronted with a large-field stimulus rotating around the vertical body axis, flies display a following behavior called "optomotor response." As neural control elements, the large tangential horizontal system (HS) cells of the lobula plate have been prime candidates for long. Here, we applied optogenetic stimulation of HS cells to evaluate their behavioral role in Drosophila. To minimize interference of the optical activation of channelrhodopsin-2 with the visual perception of the flies, we used a bistable variant called ChR2-C128S. By applying pulses of blue and yellow light, we first demonstrate electrophysiologically that lobula plate tangential cells can be activated and deactivated repeatedly with no evident change in depolarization strength over trials. We next show that selective optogenetic activation of HS cells elicits robust yaw head movements and yaw turning responses in fixed and tethered flying flies, respectively.
Journal of Neuroscience, 2005
Genetically encoded fluorescent probes of neural activity represent new promising tools for syste... more Genetically encoded fluorescent probes of neural activity represent new promising tools for systems neuroscience. Here, we present a comparative in vivo analysis of 10 different genetically encoded calcium indicators, as well as the pH-sensitive synapto-pHluorin. We analyzed their fluorescence changes in presynaptic boutons of the Drosophila larval neuromuscular junction. Robust neural activity did not result in any or noteworthy fluorescence changes when Flash-Pericam, Camgaroo-1, and Camgaroo-2 were expressed. However, calculated on the raw data, fractional fluorescence changes up to 18% were reported by synapto-pHluorin, Yellow Cameleon 2.0, 2.3, and 3.3, Inverse-Pericam, GCaMP1.3, GCaMP1.6, and the troponin C-based calcium sensor TN-L15. The response characteristics of all of these indicators differed considerably from each other, with GCaMP1.6 reporting high rates of neural activity with the largest and fastest fluorescence changes. However, GCaMP1.6 suffered from photobleaching, whereas the fluorescence signals of the doublechromophore indicators were in general smaller but more photostable and reproducible, with TN-L15 showing the fastest rise of the signals at lower activity rates. We show for GCaMP1.3 and YC3.3 that an expanded range of neural activity evoked fairly linear fluorescence changes and a corresponding linear increase in the signal-to-noise ratio (SNR). The expression level of the indicator biased the signal kinetics and SNR, whereas the signal amplitude was independent. The presented data will be useful for in vivo experiments with respect to the selection of an appropriate indicator, as well as for the correct interpretation of the optical signals.
Neuron, 2011
Recent experiments have shown that motion detection in Drosophila starts with splitting the visua... more Recent experiments have shown that motion detection in Drosophila starts with splitting the visual input into two parallel channels encoding brightness increments (ON) or decrements (OFF). This suggests the existence of either two (ON-ON, OFF-OFF) or four (for all pairwise interactions) separate motion detectors. To decide between these possibilities, we stimulated flies using sequences of ON and OFF brightness pulses while recording from motionsensitive tangential cells. We found direction-selective responses to sequences of same sign (ON-ON, OFF-OFF), but not of opposite sign (ON-OFF, OFF-ON), refuting the existence of four separate detectors. Based on further measurements, we propose a model that reproduces a variety of additional experimental data sets, including ones that were previously interpreted as support for four separate detectors. Our experiments and the derived model mark an important step in guiding further dissection of the fly motion detection circuit.
Nature, 2010
Motion vision is a major function of all visual systems, yet the underlying neural mechanisms and... more Motion vision is a major function of all visual systems, yet the underlying neural mechanisms and circuits are still elusive. In the lamina, the first optic neuropile of Drosophila melanogaster, photoreceptor signals split into five parallel pathways, L1-L5 1 .
Journal of Neurophysiology, 2010
Motion vision is essential for navigating through the environment. Due to its genetic amenability... more Motion vision is essential for navigating through the environment. Due to its genetic amenability, the fruit fly Drosophila has been serving for a lengthy period as a model organism for studying optomotor behavior as elicited by large-field horizontal motion. However, the neurons underlying the control of this behavior have not been studied in Drosophila so far. Here we report the first whole cell recordings from three cells of the horizontal system (HSN, HSE, and HSS) in the lobula plate of Drosophila. All three HS cells are tuned to large-field horizontal motion in a direction-selective way; they become excited by front-to-back motion and inhibited by back-to-front motion in the ipsilateral field of view. The response properties of HS cells such as contrast and velocity dependence are in accordance with the correlation-type model of motion detection. Neurobiotin injection suggests extensive coupling among ipsilateral HS cells and additional coupling to tangential cells that have their dendrites in the contralateral hemisphere of the brain. This connectivity scheme accounts for the complex layout of their receptive fields and explains their sensitivity both to ipsilateral and to contralateral motion. Thus the main response properties of Drosophila HS cells are strikingly similar to the responses of their counterparts in the blowfly Calliphora, although we found substantial differences with respect to their dendritic structure and connectivity. This long-awaited functional characterization of HS cells in Drosophila provides the basis for the future dissection of optomotor behavior and the underlying neural circuitry by combining genetics, physiology, and behavior.
The Journal of Comparative Neurology, 2007
In flies, the large tangential cells of the lobula plate represent an important processing center... more In flies, the large tangential cells of the lobula plate represent an important processing center for visual navigation based on optic flow. Although the visual response properties of these cells have been well studied in blowflies, information on their synaptic organization is mostly lacking. Here we study the distribution of presynaptic release and postsynaptic inhibitory sites in the same set of cells in Drosophila melanogaster. By making use of transgenic tools and immunohistochemistry, our results suggest that HS and VS cells of Drosophila express gamma-aminobutyric acid (GABA) receptors in their dendritic region within the lobula plate, thus being postsynaptic to inhibitory input there. At their axon terminals in the protocerebrum, both cell types express synaptobrevin, suggesting the presence of presynaptic specializations there. HS- and VS-cell terminals additionally show evidence for postsynaptic GABAergic input, superimposed on this synaptic polarity. Our findings are in line with the general circuit for visual motion detection and receptive field properties as postulated from electrophysiological and optical recordings in blowflies, suggesting a similar functional organization of lobula plate tangential cells in the two species.
Current Biology, 2008
The crystalline-like structure of the optic lobes of the fruit fly Drosophila melanogaster has ma... more The crystalline-like structure of the optic lobes of the fruit fly Drosophila melanogaster has made them a model system for the study of neuronal cell-fate determination, axonal path finding, and target selection. For functional studies, however, the small size of the constituting visual interneurons has so far presented a formidable barrier. We have overcome this problem by establishing in vivo whole-cell recordings [1] from genetically targeted visual interneurons of Drosophila. Here, we describe the response properties of six motionsensitive large-field neurons in the lobula plate that form a network consisting of individually identifiable, directionally selective cells most sensitive to vertical image motion (VS cells [2,). Individual VS cell responses to visual motion stimuli exhibit all the characteristics that are indicative of presynaptic input from elementary motion detectors of the correlation type . Different VS cells possess distinct receptive fields that are arranged sequentially along the eye's azimuth, corresponding to their characteristic cellular morphology and position within the retinotopically organized lobula plate. In addition, lateral connections between individual VS cells cause strongly overlapping receptive fields that are wider than expected from their dendritic input. Our results suggest that motion vision in different dipteran fly species is accomplished in similar circuitries and according to common algorithmic rules. The underlying neural mechanisms of population coding within the VS cell network and of elementary motion detection, respectively, can now be analyzed by the combination of electrophysiology and genetic intervention in Drosophila.
In bright light, cone-photoreceptors are active and colour vision derives from a comparison of si... more In bright light, cone-photoreceptors are active and colour vision derives from a comparison of signals in cones with different visual pigments. This comparison begins in the retina, where certain retinal ganglion cells have 'colour-opponent' visual responses— excited by light of one colour and suppressed by another colour 1. In dim light, rod-photoreceptors are active, but colour vision is impossible because they all use the same visual pigment. Instead, the rod signals are thought to splice into retinal circuits at various points, in synergy with the cone signals 2. Here we report a new circuit for colour vision that challenges these expectations. A genetically identified type of mouse retinal ganglion cell called JAMB (J-RGC) 3 , was found to have colour-opponent responses, OFF to ultraviolet (UV) light and ON to green light. Although the mouse retina contains a green-sensitive cone, the ON response instead originates in rods. Rods and cones both contribute to the response over several decades of light intensity. Remarkably, the rod signal in this circuit is antagonistic to that from cones. For rodents, this UV-green channel may play a role in social communication, as suggested by spectral measurements from the environment. In the human retina, all of the components for this circuit exist as well, and its function can explain certain experiences of colour in dim lights, such as a 'blue shift' in twilight. The discovery of this genetically defined pathway will enable new targeted studies of colour processing in the brain. Like most mammals, the mouse has one type of rod and two types of cone photoreceptors, with absorption maxima in the ultraviolet (S pigment) and green (M pigment) region of the spectrum. As in other small mammals, the retinal organization of the cones is inhomogeneous: the M and S pigments are largely segregated in the dorsal and ventral retina, respectively 4. At the level of ganglion cells, the spectral sensitivity essentially follows this cone distribution 5,6 , which severely limits any local comparison of signals across cone pigments. Because behavioural experiments show that mice can indeed 'see colour' 7 , it has been suggested that colour vision in mice operates on very different principles from primates 8. Surprisingly, as we demonstrate here, the mouse does have a dedicated ganglion cell type with clearly opponent responses to light of different wavelengths. It uses an unexpected retinal circuit that circumvents the obstacle caused by the spatial segregation of cone pigments. We recorded the visual responses of J-RGCs in the retina of a mouse line that labels these neurons fluorescently 3 (Fig. 1a). When probed with white light, the receptive field has OFF-type sensitivity in the centre and ON-type sensitivity in the surround (Fig. 1b). As reported previously, the surround is stronger on the side of the asymmetric den-dritic arbor 3. Stimulation using coloured lights led to a surprise. Many J-RGCs produce an OFF response to uniform UV light,
Nature, 2016
In bright light, cone-photoreceptors are active and colour vision derives from a comparison of si... more In bright light, cone-photoreceptors are active and colour vision derives from a comparison of signals in cones with different visual pigments. This comparison begins in the retina, where certain retinal ganglion cells have 'colour-opponent' visual responses-excited by light of one colour and suppressed by another colour. In dim light, rod-photoreceptors are active, but colour vision is impossible because they all use the same visual pigment. Instead, the rod signals are thought to splice into retinal circuits at various points, in synergy with the cone signals. Here we report a new circuit for colour vision that challenges these expectations. A genetically identified type of mouse retinal ganglion cell called JAMB (J-RGC), was found to have colour-opponent responses, OFF to ultraviolet (UV) light and ON to green light. Although the mouse retina contains a green-sensitive cone, the ON response instead originates in rods. Rods and cones both contribute to the response over several decades of light intensity. Remarkably, the rod signal in this circuit is antagonistic to that from cones. For rodents, this UV-green channel may play a role in social communication, as suggested by spectral measurements from the environment. In the human retina, all of the components for this circuit exist as well, and its function can explain certain experiences of colour in dim lights, such as a 'blue shift' in twilight. The discovery of this genetically defined pathway will enable new targeted studies of colour processing in the brain.
Journal of Neuroscience, 2013
In the fly Drosophila melanogaster, photoreceptor input to motion vision is split into two parall... more In the fly Drosophila melanogaster, photoreceptor input to motion vision is split into two parallel pathways as represented by first-order interneurons L1 and L2 (Rister et al., 2007; Joesch et al., 2010). However, how these pathways are functionally specialized remains controversial. One study (Eichner et al., 2011) proposed that the L1-pathway evaluates only sequences of brightness increments (ON-ON), while the L2-pathway processes exclusively brightness decrements (OFF-OFF). Another study (Clark et al., 2011) proposed that each of the two pathways evaluates both ON-ON and OFF-OFF sequences.
Journal of Neuroscience, 2013
When confronted with a large-field stimulus rotating around the vertical body axis, flies display... more When confronted with a large-field stimulus rotating around the vertical body axis, flies display a following behavior called "optomotor response." As neural control elements, the large tangential horizontal system (HS) cells of the lobula plate have been prime candidates for long. Here, we applied optogenetic stimulation of HS cells to evaluate their behavioral role in Drosophila. To minimize interference of the optical activation of channelrhodopsin-2 with the visual perception of the flies, we used a bistable variant called ChR2-C128S. By applying pulses of blue and yellow light, we first demonstrate electrophysiologically that lobula plate tangential cells can be activated and deactivated repeatedly with no evident change in depolarization strength over trials. We next show that selective optogenetic activation of HS cells elicits robust yaw head movements and yaw turning responses in fixed and tethered flying flies, respectively.
Journal of Neuroscience, 2005
Genetically encoded fluorescent probes of neural activity represent new promising tools for syste... more Genetically encoded fluorescent probes of neural activity represent new promising tools for systems neuroscience. Here, we present a comparative in vivo analysis of 10 different genetically encoded calcium indicators, as well as the pH-sensitive synapto-pHluorin. We analyzed their fluorescence changes in presynaptic boutons of the Drosophila larval neuromuscular junction. Robust neural activity did not result in any or noteworthy fluorescence changes when Flash-Pericam, Camgaroo-1, and Camgaroo-2 were expressed. However, calculated on the raw data, fractional fluorescence changes up to 18% were reported by synapto-pHluorin, Yellow Cameleon 2.0, 2.3, and 3.3, Inverse-Pericam, GCaMP1.3, GCaMP1.6, and the troponin C-based calcium sensor TN-L15. The response characteristics of all of these indicators differed considerably from each other, with GCaMP1.6 reporting high rates of neural activity with the largest and fastest fluorescence changes. However, GCaMP1.6 suffered from photobleaching, whereas the fluorescence signals of the doublechromophore indicators were in general smaller but more photostable and reproducible, with TN-L15 showing the fastest rise of the signals at lower activity rates. We show for GCaMP1.3 and YC3.3 that an expanded range of neural activity evoked fairly linear fluorescence changes and a corresponding linear increase in the signal-to-noise ratio (SNR). The expression level of the indicator biased the signal kinetics and SNR, whereas the signal amplitude was independent. The presented data will be useful for in vivo experiments with respect to the selection of an appropriate indicator, as well as for the correct interpretation of the optical signals.
Neuron, 2011
Recent experiments have shown that motion detection in Drosophila starts with splitting the visua... more Recent experiments have shown that motion detection in Drosophila starts with splitting the visual input into two parallel channels encoding brightness increments (ON) or decrements (OFF). This suggests the existence of either two (ON-ON, OFF-OFF) or four (for all pairwise interactions) separate motion detectors. To decide between these possibilities, we stimulated flies using sequences of ON and OFF brightness pulses while recording from motionsensitive tangential cells. We found direction-selective responses to sequences of same sign (ON-ON, OFF-OFF), but not of opposite sign (ON-OFF, OFF-ON), refuting the existence of four separate detectors. Based on further measurements, we propose a model that reproduces a variety of additional experimental data sets, including ones that were previously interpreted as support for four separate detectors. Our experiments and the derived model mark an important step in guiding further dissection of the fly motion detection circuit.
Nature, 2010
Motion vision is a major function of all visual systems, yet the underlying neural mechanisms and... more Motion vision is a major function of all visual systems, yet the underlying neural mechanisms and circuits are still elusive. In the lamina, the first optic neuropile of Drosophila melanogaster, photoreceptor signals split into five parallel pathways, L1-L5 1 .
Journal of Neurophysiology, 2010
Motion vision is essential for navigating through the environment. Due to its genetic amenability... more Motion vision is essential for navigating through the environment. Due to its genetic amenability, the fruit fly Drosophila has been serving for a lengthy period as a model organism for studying optomotor behavior as elicited by large-field horizontal motion. However, the neurons underlying the control of this behavior have not been studied in Drosophila so far. Here we report the first whole cell recordings from three cells of the horizontal system (HSN, HSE, and HSS) in the lobula plate of Drosophila. All three HS cells are tuned to large-field horizontal motion in a direction-selective way; they become excited by front-to-back motion and inhibited by back-to-front motion in the ipsilateral field of view. The response properties of HS cells such as contrast and velocity dependence are in accordance with the correlation-type model of motion detection. Neurobiotin injection suggests extensive coupling among ipsilateral HS cells and additional coupling to tangential cells that have their dendrites in the contralateral hemisphere of the brain. This connectivity scheme accounts for the complex layout of their receptive fields and explains their sensitivity both to ipsilateral and to contralateral motion. Thus the main response properties of Drosophila HS cells are strikingly similar to the responses of their counterparts in the blowfly Calliphora, although we found substantial differences with respect to their dendritic structure and connectivity. This long-awaited functional characterization of HS cells in Drosophila provides the basis for the future dissection of optomotor behavior and the underlying neural circuitry by combining genetics, physiology, and behavior.
The Journal of Comparative Neurology, 2007
In flies, the large tangential cells of the lobula plate represent an important processing center... more In flies, the large tangential cells of the lobula plate represent an important processing center for visual navigation based on optic flow. Although the visual response properties of these cells have been well studied in blowflies, information on their synaptic organization is mostly lacking. Here we study the distribution of presynaptic release and postsynaptic inhibitory sites in the same set of cells in Drosophila melanogaster. By making use of transgenic tools and immunohistochemistry, our results suggest that HS and VS cells of Drosophila express gamma-aminobutyric acid (GABA) receptors in their dendritic region within the lobula plate, thus being postsynaptic to inhibitory input there. At their axon terminals in the protocerebrum, both cell types express synaptobrevin, suggesting the presence of presynaptic specializations there. HS- and VS-cell terminals additionally show evidence for postsynaptic GABAergic input, superimposed on this synaptic polarity. Our findings are in line with the general circuit for visual motion detection and receptive field properties as postulated from electrophysiological and optical recordings in blowflies, suggesting a similar functional organization of lobula plate tangential cells in the two species.
Current Biology, 2008
The crystalline-like structure of the optic lobes of the fruit fly Drosophila melanogaster has ma... more The crystalline-like structure of the optic lobes of the fruit fly Drosophila melanogaster has made them a model system for the study of neuronal cell-fate determination, axonal path finding, and target selection. For functional studies, however, the small size of the constituting visual interneurons has so far presented a formidable barrier. We have overcome this problem by establishing in vivo whole-cell recordings [1] from genetically targeted visual interneurons of Drosophila. Here, we describe the response properties of six motionsensitive large-field neurons in the lobula plate that form a network consisting of individually identifiable, directionally selective cells most sensitive to vertical image motion (VS cells [2,). Individual VS cell responses to visual motion stimuli exhibit all the characteristics that are indicative of presynaptic input from elementary motion detectors of the correlation type . Different VS cells possess distinct receptive fields that are arranged sequentially along the eye's azimuth, corresponding to their characteristic cellular morphology and position within the retinotopically organized lobula plate. In addition, lateral connections between individual VS cells cause strongly overlapping receptive fields that are wider than expected from their dendritic input. Our results suggest that motion vision in different dipteran fly species is accomplished in similar circuitries and according to common algorithmic rules. The underlying neural mechanisms of population coding within the VS cell network and of elementary motion detection, respectively, can now be analyzed by the combination of electrophysiology and genetic intervention in Drosophila.