Matthew Larkum | Humboldt University Berlin (original) (raw)
Papers by Matthew Larkum
Neuron, 2019
Oxytocin (OT) release by axonal terminals onto the central nucleus of the amygdala exerts anxioly... more Oxytocin (OT) release by axonal terminals onto the central nucleus of the amygdala exerts anxiolysis. To investigate which subpopulation of OT neurons contributes to this effect, we developed a novel method: virus-delivered genetic activity-induced tagging of cell ensembles (vGATE). With the vGATE method, we identified and permanently tagged a small subpopulation of OT cells, which, by optogenetic stimulation, strongly attenuated contextual fear-induced freezing, and pharmacogenetic silencing of tagged OT neurons impaired context-specific fear extinction, demonstrating that the tagged OT neurons are sufficient and necessary, respectively, to control contextual fear. Intriguingly, OT cell terminals of fear-experienced rats displayed enhanced glutamate release in the amygdala. Furthermore, rats exposed to another round of fear conditioning displayed 5-fold more activated magnocellular OT neurons in a novel environment than a familiar one, possibly for a generalized fear response. Thus, our results provide first evidence that hypothalamic OT neurons represent a fear memory engram. INTRODUCTION Emotional memory representations (also called memory engrams), such as for fear, are pivotal for animal survival. Fearassociated behaviors have evolved over millions of years in living systems, from lower to higher animals, so that they can sense, evaluate, respond, and adapt to adequately deal with dangerous situations (Mobbs et al., 2015). Fear-related disorders, such as specific phobias and post-traumatic stress disorder (PTSD), are among the most prevalent human psychiatric conditions and pose debilitating health burdens to affected individuals and immense costs to society (Kessler and Bromet, 2013). Understanding the neural basis of fear learning, expression,
PLOS Biology
Rapid advances in neuroscience have provided remarkable breakthroughs in understanding the brain ... more Rapid advances in neuroscience have provided remarkable breakthroughs in understanding the brain on many fronts. Although promising, the role of these advancements in solving the problem of consciousness is still unclear. Based on technologies conceivably within the grasp of modern neuroscience, we discuss a thought experiment in which neural activity, in the form of action potentials, is initially recorded from all the neurons in a participant’s brain during a conscious experience and then played back into the same neurons. We consider whether this artificial replay can reconstitute a conscious experience. The possible outcomes of this experiment unravel hidden costs and pitfalls in understanding consciousness from the neurosciences’ perspective and challenge the conventional wisdom that causally links action potentials and consciousness.
Rapid advances in neuroscience have provided remarkable breakthroughs in understanding the brain ... more Rapid advances in neuroscience have provided remarkable breakthroughs in understanding the brain on many fronts. Although promising, the role of these advancements in solving the problem of consciousness is still unclear. Based on technologies conceivably within the grasp of modern neuroscience, we envision an experiment where action potentials are initially recorded from all the neurons in a subject’s brain during a conscious experience and then played back into the same neurons. We examine whether this artificial replay can reconstitute a conscious experience. The possible outcomes of this experiment unravel hidden costs and pitfalls in understanding consciousness from the neurosciences’ perspective.
doi: 10.1152/jn.00082.2007 You might find this additional info useful... Supplementary material f... more doi: 10.1152/jn.00082.2007 You might find this additional info useful... Supplementary material for this article can be found at:
Optica, 2021
Optical imaging techniques are widely used in biological research, but their penetration depth is... more Optical imaging techniques are widely used in biological research, but their penetration depth is limited by tissue scattering. Wavefront shaping techniques are able to overcome this problem in principle, but are often slow and their performance depends on the sample. This greatly reduces their practicability for biological applications. Here we present a scattering compensation technique based on three-photon (3P) excitation, which converges faster than comparable two-photon (2P) techniques and works reliably even on densely labeled samples, where 2P approaches fail. To demonstrate its usability and advantages for biomedical imaging we apply it to the imaging of dendritic spines on GFP-labeled layer 5 neurons in an anesthetized mouse.
Frontiers in Cellular Neuroscience, 2021
Synergistic interactions between independent synaptic input streams may fundamentally change the ... more Synergistic interactions between independent synaptic input streams may fundamentally change the action potential (AP) output. Using partial information decomposition, we demonstrate here a substantial contribution of synergy between somatic and apical dendritic inputs to the information in the AP output of L5b pyramidal neurons. Activation of dendritic GABAB receptors (GABABRs), known to decrease APs in vivo, potently decreased synergy and increased somatic control of AP output. Synergy was the result of the voltage-dependence of the transfer resistance between dendrite and soma, which showed a two-fold increase per 28.7 mV dendritic depolarization. GIRK channels activated by dendritic GABABRs decreased voltage-dependent transfer resistances and AP output. In contrast, inhibition of dendritic L-type Ca2+ channels prevented high-frequency bursts of APs, but did not affect dendro-somatic synergy. Finally, we show that NDNF-positive neurogliaform cells effectively control somatic AP v...
Signals sent back to the neocortex from the hippocampus control the long-term storage of memories... more Signals sent back to the neocortex from the hippocampus control the long-term storage of memories in the neocortex1,2, but the cellular mechanisms underlying this process remain elusive. Here, we show that learning is controlled by specific medial-temporal input to neocortical layer 1. To show this we used direct cortical microstimulation detection task that allowed the precise region of learning to be examined and manipulated. Chemogenetically suppressing the last stage of the medial temporal loop, i.e. perirhinal cortex input to neocortical layer 1, profoundly disrupted early memory formation but had no effect on behavior in trained animals. The learning involved the emergence of a small population of layer 5 pyramidal neurons (~10%) with significantly increased firing involving high-frequency bursts of action potentials that were also blocked by suppression of perirhinal input. Moreover, we found that dendritic excitability was correspondingly enhanced in a similarly-sized popula...
A central function of the brain is to plan, predict and imagine the effect of movement in a dynam... more A central function of the brain is to plan, predict and imagine the effect of movement in a dynamically changing environment. Here we show that in mice head fixed in a plus-maze, floating on air, and trained to pick lanes based on visual stimuli, the asymmetric movement and position of whiskers on the two sides of the face signals whether the animal is moving, turning, expecting reward or licking. We show that 1) we can decode and predict the behavioral state of the animal based on this asymmetry, 2) that tactile input from whiskers indicates little about the behavioral state, and 3) that movement of the nose correlates with asymmetry, indicating that facial expression of the mouse is itself correlated with behavioral state. Amazingly, the movement of whiskers – a behavior that is not instructed or necessary in the task--informs an observer about what a mouse is doing in the maze. Thus, these mobile tactile sensors reflect a behavioral and movement-preparation state of the mouse.
Journal of Neurophysiology, 1998
Larkum, Matthew E., Thomas Launey, Alexander Dityatev, and Hans-R. Lüscher. Integration of excita... more Larkum, Matthew E., Thomas Launey, Alexander Dityatev, and Hans-R. Lüscher. Integration of excitatory postsynaptic potentials in dendrites of motoneurons of rat spinal cord slice cultures. J. Neurophysiol. 80: 924–935, 1998. We examined the attenuation and integration of spontaneous excitatory postsynaptic potentials (sEPSPs) in the dendrites of presumed motoneurons (MNs) of organotypic rat spinal cord cultures. Simultaneous whole cell recordings in current-clamp mode were made from either the soma and a dendrite or from two dendrites. Direct comparison of the two voltage recordings revealed that the membrane potentials at the two recording sites followed each other very closely except for the fast-rising phases of the EPSPs. The dendritic recording represented a low-pass filtered version of the somatic recording and vice versa. A computer-assisted method was developed to fit the sEPSPs with a generalized α-function for measuring their amplitudes and rise times (10–90%). The mean EP...
Science, 2016
Now you feel it, now you don't What determines the detection of a sensory stimulus? To addres... more Now you feel it, now you don't What determines the detection of a sensory stimulus? To address this question, Takahashi et al. combined in vivo two-photon imaging, electrophysiology, optogenetics, and behavioral analysis in a study of mice. Calcium signals in apical dendrites of pyramidal neurons in the somatosensory cortex controlled the perceptual threshold of the mice's whiskers. Strong reduction of dendritic calcium signaling impaired the perceptual detection threshold so that an identical stimulus could no longer be noticed. Science , this issue p. 1587
Neuron, Jan 18, 2006
The apical tuft of layer 5 pyramidal neurons is innervated by a large number of inhibitory inputs... more The apical tuft of layer 5 pyramidal neurons is innervated by a large number of inhibitory inputs with unknown functions. Here, we studied the functional consequences and underlying molecular mechanisms of apical inhibition on dendritic spike activity. Extracellular stimulation of layer 1, during blockade of glutamatergic transmission, inhibited the dendritic Ca2+ spike for up to 400 ms. Activation of metabotropic GABAB receptors was responsible for a gradual and long-lasting inhibitory effect, whereas GABAA receptors mediated a short-lasting (approximately 150 ms) inhibition. Our results suggest that the mechanism underlying the GABAB inhibition of Ca2+ spikes involves direct blockade of dendritic Ca2+ channels. By using knockout mice for the two predominant GABAB1 isoforms, GABAB1a and GABAB1b, we showed that postsynaptic inhibition of Ca2+ spikes is mediated by GABAB1b, whereas presynaptic inhibition of GABA release is mediated by GABAB1a. We conclude that the molecular subtypes ...
Journal of Neuroscience, 2007
Layer 2/3 (L2/3) pyramidal neurons are the most abundant cells of the neocortex. Despite their ke... more Layer 2/3 (L2/3) pyramidal neurons are the most abundant cells of the neocortex. Despite their key position in the cortical microcircuit, synaptic integration in dendrites of L2/3 neurons is far less understood than in L5 pyramidal cell dendrites, mainly because of the difficulties in obtaining electrical recordings from thin dendrites. Here we directly measured passive and active properties of the apical dendrites of L2/3 neurons in rat brain slices using dual dendritic-somatic patch-clamp recordings and calcium imaging. Unlike L5 cells, L2/3 dendrites displayed little sag in response to long current pulses, which suggests a low density of I h in the dendrites and soma. This was also consistent with a slight increase in input resistance with distance from the soma. Brief current injections into the apical dendrite evoked relatively short (half-width 2-4 ms) dendritic spikes that were isolated from the soma for near-threshold currents at sites beyond the middle of the apical dendrite. Regenerative dendritic potentials and large concomitant calcium transients were also elicited by trains of somatic action potentials (APs) above a critical frequency (130 Hz), which was slightly higher than in L5 neurons. Initiation of dendritic spikes was facilitated by backpropagating somatic APs and could cause an additional AP at the soma. As in L5 neurons, we found that distal dendritic calcium transients are sensitive to a long-lasting block by GABAergic inhibition. We conclude that L2/3 pyramidal neurons can generate dendritic spikes, sharing with L5 pyramidal neurons fundamental properties of dendritic excitability and control by inhibition.
Science, 2009
Fine Dendrites Fire Differently The pyramidal neuron is the basic computational unit in the brain... more Fine Dendrites Fire Differently The pyramidal neuron is the basic computational unit in the brain cortex. Its distal tuft dendrite is heavily innervated by horizontal fibers coursing through cortical layer-I providing long-range corticocortical and thalamocortical associational input. Larkum et al. (p. 756 ) investigated whether the apical tuft dendrites of layer-5 neocortical pyramidal neurons, like basal dendrites, generate n -methyl- d -aspartate (NMDA) spikes using two-photon–guided direct dendritic recording, glutamate uncaging, and modeling. NMDA spikes could be evoked in the distal tuft dendrites, while Ca 2+ spikes could be triggered at the bifurcation points. Block of the hyperpolarization-activated current enhanced these NMDA spikes. Thus, the generation of NMDA spikes is a general principle of thin, basal, and tuft dendrites.
PLoS Biology, 2004
Genetically encoded fluorescent calcium indicator proteins (FCIPs) are promising tools to study c... more Genetically encoded fluorescent calcium indicator proteins (FCIPs) are promising tools to study calcium dynamics in many activity-dependent molecular and cellular processes. Great hopes-for the measurement of population activity, in particular-have therefore been placed on calcium indicators derived from the green fluorescent protein and their expression in (selected) neuronal populations. Calcium transients can rise within milliseconds, making them suitable as reporters of fast neuronal activity. We here report the production of stable transgenic mouse lines with two different functional calcium indicators, inverse pericam and camgaroo-2, under the control of the tetracycline-inducible promoter. Using a variety of in vitro and in vivo assays, we find that stimuli known to increase intracellular calcium concentration (somatically triggered action potentials (APs) and synaptic and sensory stimulation) can cause substantial and rapid changes in FCIP fluorescence of inverse pericam and camgaroo-2.
Nature Neuroscience, 2002
We provide a functional measure, the synaptic information efficacy (SIE), to assess the impact of... more We provide a functional measure, the synaptic information efficacy (SIE), to assess the impact of synaptic input on spike output. SIE is the mutual information shared by the presynaptic input and postsynaptic output spike trains. To estimate SIE we used a method based on compression algorithms. This method detects the effect of a single synaptic input on the postsynaptic spike output in the presence of massive background synaptic activity in neuron models of progressively increasing realism. SIE increased with increases either in time locking between the input synapse activity and the output spike or in the average number of output spikes. SIE depended on the context in which the synapse operates. We also measured SIE experimentally. Systematic exploration of the effect of synaptic and dendritic parameters on the SIE offers a fresh look at the synapse as a communication device and a quantitative measure of how much the dendritic synapse informs the axon.
Nature Neuroscience, 2007
Basal dendrites receive the majority of synapses that contact neocortical pyramidal neurons, yet ... more Basal dendrites receive the majority of synapses that contact neocortical pyramidal neurons, yet our knowledge of synaptic processing in these dendrites has been hampered by their inaccessibility for electrical recordings. A new approach to patch-clamp recordings enabled us to characterize the integrative properties of these cells. Despite the short physical length of rat basal dendrites, synaptic inputs were electrotonically remote from the soma (> 30-fold excitatory postsynaptic potential (EPSP) attenuation) and back-propagating action potentials were significantly attenuated. Unitary EPSPs were location dependent, reaching large amplitudes distally (> 8 mV), yet their somatic contribution was relatively location independent. Basal dendrites support sodium and NMDA spikes, but not calcium spikes, for 75% of their length. This suggests that basal dendrites, despite their proximity to the site of action potential initiation, do not form a single basal-somatic region but rather should be considered as a separate integrative compartment favoring two integration modes: subthreshold, location-independent summation versus local amplification of incoming spatiotemporally clustered information.
Neuron, 2019
Oxytocin (OT) release by axonal terminals onto the central nucleus of the amygdala exerts anxioly... more Oxytocin (OT) release by axonal terminals onto the central nucleus of the amygdala exerts anxiolysis. To investigate which subpopulation of OT neurons contributes to this effect, we developed a novel method: virus-delivered genetic activity-induced tagging of cell ensembles (vGATE). With the vGATE method, we identified and permanently tagged a small subpopulation of OT cells, which, by optogenetic stimulation, strongly attenuated contextual fear-induced freezing, and pharmacogenetic silencing of tagged OT neurons impaired context-specific fear extinction, demonstrating that the tagged OT neurons are sufficient and necessary, respectively, to control contextual fear. Intriguingly, OT cell terminals of fear-experienced rats displayed enhanced glutamate release in the amygdala. Furthermore, rats exposed to another round of fear conditioning displayed 5-fold more activated magnocellular OT neurons in a novel environment than a familiar one, possibly for a generalized fear response. Thus, our results provide first evidence that hypothalamic OT neurons represent a fear memory engram. INTRODUCTION Emotional memory representations (also called memory engrams), such as for fear, are pivotal for animal survival. Fearassociated behaviors have evolved over millions of years in living systems, from lower to higher animals, so that they can sense, evaluate, respond, and adapt to adequately deal with dangerous situations (Mobbs et al., 2015). Fear-related disorders, such as specific phobias and post-traumatic stress disorder (PTSD), are among the most prevalent human psychiatric conditions and pose debilitating health burdens to affected individuals and immense costs to society (Kessler and Bromet, 2013). Understanding the neural basis of fear learning, expression,
PLOS Biology
Rapid advances in neuroscience have provided remarkable breakthroughs in understanding the brain ... more Rapid advances in neuroscience have provided remarkable breakthroughs in understanding the brain on many fronts. Although promising, the role of these advancements in solving the problem of consciousness is still unclear. Based on technologies conceivably within the grasp of modern neuroscience, we discuss a thought experiment in which neural activity, in the form of action potentials, is initially recorded from all the neurons in a participant’s brain during a conscious experience and then played back into the same neurons. We consider whether this artificial replay can reconstitute a conscious experience. The possible outcomes of this experiment unravel hidden costs and pitfalls in understanding consciousness from the neurosciences’ perspective and challenge the conventional wisdom that causally links action potentials and consciousness.
Rapid advances in neuroscience have provided remarkable breakthroughs in understanding the brain ... more Rapid advances in neuroscience have provided remarkable breakthroughs in understanding the brain on many fronts. Although promising, the role of these advancements in solving the problem of consciousness is still unclear. Based on technologies conceivably within the grasp of modern neuroscience, we envision an experiment where action potentials are initially recorded from all the neurons in a subject’s brain during a conscious experience and then played back into the same neurons. We examine whether this artificial replay can reconstitute a conscious experience. The possible outcomes of this experiment unravel hidden costs and pitfalls in understanding consciousness from the neurosciences’ perspective.
doi: 10.1152/jn.00082.2007 You might find this additional info useful... Supplementary material f... more doi: 10.1152/jn.00082.2007 You might find this additional info useful... Supplementary material for this article can be found at:
Optica, 2021
Optical imaging techniques are widely used in biological research, but their penetration depth is... more Optical imaging techniques are widely used in biological research, but their penetration depth is limited by tissue scattering. Wavefront shaping techniques are able to overcome this problem in principle, but are often slow and their performance depends on the sample. This greatly reduces their practicability for biological applications. Here we present a scattering compensation technique based on three-photon (3P) excitation, which converges faster than comparable two-photon (2P) techniques and works reliably even on densely labeled samples, where 2P approaches fail. To demonstrate its usability and advantages for biomedical imaging we apply it to the imaging of dendritic spines on GFP-labeled layer 5 neurons in an anesthetized mouse.
Frontiers in Cellular Neuroscience, 2021
Synergistic interactions between independent synaptic input streams may fundamentally change the ... more Synergistic interactions between independent synaptic input streams may fundamentally change the action potential (AP) output. Using partial information decomposition, we demonstrate here a substantial contribution of synergy between somatic and apical dendritic inputs to the information in the AP output of L5b pyramidal neurons. Activation of dendritic GABAB receptors (GABABRs), known to decrease APs in vivo, potently decreased synergy and increased somatic control of AP output. Synergy was the result of the voltage-dependence of the transfer resistance between dendrite and soma, which showed a two-fold increase per 28.7 mV dendritic depolarization. GIRK channels activated by dendritic GABABRs decreased voltage-dependent transfer resistances and AP output. In contrast, inhibition of dendritic L-type Ca2+ channels prevented high-frequency bursts of APs, but did not affect dendro-somatic synergy. Finally, we show that NDNF-positive neurogliaform cells effectively control somatic AP v...
Signals sent back to the neocortex from the hippocampus control the long-term storage of memories... more Signals sent back to the neocortex from the hippocampus control the long-term storage of memories in the neocortex1,2, but the cellular mechanisms underlying this process remain elusive. Here, we show that learning is controlled by specific medial-temporal input to neocortical layer 1. To show this we used direct cortical microstimulation detection task that allowed the precise region of learning to be examined and manipulated. Chemogenetically suppressing the last stage of the medial temporal loop, i.e. perirhinal cortex input to neocortical layer 1, profoundly disrupted early memory formation but had no effect on behavior in trained animals. The learning involved the emergence of a small population of layer 5 pyramidal neurons (~10%) with significantly increased firing involving high-frequency bursts of action potentials that were also blocked by suppression of perirhinal input. Moreover, we found that dendritic excitability was correspondingly enhanced in a similarly-sized popula...
A central function of the brain is to plan, predict and imagine the effect of movement in a dynam... more A central function of the brain is to plan, predict and imagine the effect of movement in a dynamically changing environment. Here we show that in mice head fixed in a plus-maze, floating on air, and trained to pick lanes based on visual stimuli, the asymmetric movement and position of whiskers on the two sides of the face signals whether the animal is moving, turning, expecting reward or licking. We show that 1) we can decode and predict the behavioral state of the animal based on this asymmetry, 2) that tactile input from whiskers indicates little about the behavioral state, and 3) that movement of the nose correlates with asymmetry, indicating that facial expression of the mouse is itself correlated with behavioral state. Amazingly, the movement of whiskers – a behavior that is not instructed or necessary in the task--informs an observer about what a mouse is doing in the maze. Thus, these mobile tactile sensors reflect a behavioral and movement-preparation state of the mouse.
Journal of Neurophysiology, 1998
Larkum, Matthew E., Thomas Launey, Alexander Dityatev, and Hans-R. Lüscher. Integration of excita... more Larkum, Matthew E., Thomas Launey, Alexander Dityatev, and Hans-R. Lüscher. Integration of excitatory postsynaptic potentials in dendrites of motoneurons of rat spinal cord slice cultures. J. Neurophysiol. 80: 924–935, 1998. We examined the attenuation and integration of spontaneous excitatory postsynaptic potentials (sEPSPs) in the dendrites of presumed motoneurons (MNs) of organotypic rat spinal cord cultures. Simultaneous whole cell recordings in current-clamp mode were made from either the soma and a dendrite or from two dendrites. Direct comparison of the two voltage recordings revealed that the membrane potentials at the two recording sites followed each other very closely except for the fast-rising phases of the EPSPs. The dendritic recording represented a low-pass filtered version of the somatic recording and vice versa. A computer-assisted method was developed to fit the sEPSPs with a generalized α-function for measuring their amplitudes and rise times (10–90%). The mean EP...
Science, 2016
Now you feel it, now you don't What determines the detection of a sensory stimulus? To addres... more Now you feel it, now you don't What determines the detection of a sensory stimulus? To address this question, Takahashi et al. combined in vivo two-photon imaging, electrophysiology, optogenetics, and behavioral analysis in a study of mice. Calcium signals in apical dendrites of pyramidal neurons in the somatosensory cortex controlled the perceptual threshold of the mice's whiskers. Strong reduction of dendritic calcium signaling impaired the perceptual detection threshold so that an identical stimulus could no longer be noticed. Science , this issue p. 1587
Neuron, Jan 18, 2006
The apical tuft of layer 5 pyramidal neurons is innervated by a large number of inhibitory inputs... more The apical tuft of layer 5 pyramidal neurons is innervated by a large number of inhibitory inputs with unknown functions. Here, we studied the functional consequences and underlying molecular mechanisms of apical inhibition on dendritic spike activity. Extracellular stimulation of layer 1, during blockade of glutamatergic transmission, inhibited the dendritic Ca2+ spike for up to 400 ms. Activation of metabotropic GABAB receptors was responsible for a gradual and long-lasting inhibitory effect, whereas GABAA receptors mediated a short-lasting (approximately 150 ms) inhibition. Our results suggest that the mechanism underlying the GABAB inhibition of Ca2+ spikes involves direct blockade of dendritic Ca2+ channels. By using knockout mice for the two predominant GABAB1 isoforms, GABAB1a and GABAB1b, we showed that postsynaptic inhibition of Ca2+ spikes is mediated by GABAB1b, whereas presynaptic inhibition of GABA release is mediated by GABAB1a. We conclude that the molecular subtypes ...
Journal of Neuroscience, 2007
Layer 2/3 (L2/3) pyramidal neurons are the most abundant cells of the neocortex. Despite their ke... more Layer 2/3 (L2/3) pyramidal neurons are the most abundant cells of the neocortex. Despite their key position in the cortical microcircuit, synaptic integration in dendrites of L2/3 neurons is far less understood than in L5 pyramidal cell dendrites, mainly because of the difficulties in obtaining electrical recordings from thin dendrites. Here we directly measured passive and active properties of the apical dendrites of L2/3 neurons in rat brain slices using dual dendritic-somatic patch-clamp recordings and calcium imaging. Unlike L5 cells, L2/3 dendrites displayed little sag in response to long current pulses, which suggests a low density of I h in the dendrites and soma. This was also consistent with a slight increase in input resistance with distance from the soma. Brief current injections into the apical dendrite evoked relatively short (half-width 2-4 ms) dendritic spikes that were isolated from the soma for near-threshold currents at sites beyond the middle of the apical dendrite. Regenerative dendritic potentials and large concomitant calcium transients were also elicited by trains of somatic action potentials (APs) above a critical frequency (130 Hz), which was slightly higher than in L5 neurons. Initiation of dendritic spikes was facilitated by backpropagating somatic APs and could cause an additional AP at the soma. As in L5 neurons, we found that distal dendritic calcium transients are sensitive to a long-lasting block by GABAergic inhibition. We conclude that L2/3 pyramidal neurons can generate dendritic spikes, sharing with L5 pyramidal neurons fundamental properties of dendritic excitability and control by inhibition.
Science, 2009
Fine Dendrites Fire Differently The pyramidal neuron is the basic computational unit in the brain... more Fine Dendrites Fire Differently The pyramidal neuron is the basic computational unit in the brain cortex. Its distal tuft dendrite is heavily innervated by horizontal fibers coursing through cortical layer-I providing long-range corticocortical and thalamocortical associational input. Larkum et al. (p. 756 ) investigated whether the apical tuft dendrites of layer-5 neocortical pyramidal neurons, like basal dendrites, generate n -methyl- d -aspartate (NMDA) spikes using two-photon–guided direct dendritic recording, glutamate uncaging, and modeling. NMDA spikes could be evoked in the distal tuft dendrites, while Ca 2+ spikes could be triggered at the bifurcation points. Block of the hyperpolarization-activated current enhanced these NMDA spikes. Thus, the generation of NMDA spikes is a general principle of thin, basal, and tuft dendrites.
PLoS Biology, 2004
Genetically encoded fluorescent calcium indicator proteins (FCIPs) are promising tools to study c... more Genetically encoded fluorescent calcium indicator proteins (FCIPs) are promising tools to study calcium dynamics in many activity-dependent molecular and cellular processes. Great hopes-for the measurement of population activity, in particular-have therefore been placed on calcium indicators derived from the green fluorescent protein and their expression in (selected) neuronal populations. Calcium transients can rise within milliseconds, making them suitable as reporters of fast neuronal activity. We here report the production of stable transgenic mouse lines with two different functional calcium indicators, inverse pericam and camgaroo-2, under the control of the tetracycline-inducible promoter. Using a variety of in vitro and in vivo assays, we find that stimuli known to increase intracellular calcium concentration (somatically triggered action potentials (APs) and synaptic and sensory stimulation) can cause substantial and rapid changes in FCIP fluorescence of inverse pericam and camgaroo-2.
Nature Neuroscience, 2002
We provide a functional measure, the synaptic information efficacy (SIE), to assess the impact of... more We provide a functional measure, the synaptic information efficacy (SIE), to assess the impact of synaptic input on spike output. SIE is the mutual information shared by the presynaptic input and postsynaptic output spike trains. To estimate SIE we used a method based on compression algorithms. This method detects the effect of a single synaptic input on the postsynaptic spike output in the presence of massive background synaptic activity in neuron models of progressively increasing realism. SIE increased with increases either in time locking between the input synapse activity and the output spike or in the average number of output spikes. SIE depended on the context in which the synapse operates. We also measured SIE experimentally. Systematic exploration of the effect of synaptic and dendritic parameters on the SIE offers a fresh look at the synapse as a communication device and a quantitative measure of how much the dendritic synapse informs the axon.
Nature Neuroscience, 2007
Basal dendrites receive the majority of synapses that contact neocortical pyramidal neurons, yet ... more Basal dendrites receive the majority of synapses that contact neocortical pyramidal neurons, yet our knowledge of synaptic processing in these dendrites has been hampered by their inaccessibility for electrical recordings. A new approach to patch-clamp recordings enabled us to characterize the integrative properties of these cells. Despite the short physical length of rat basal dendrites, synaptic inputs were electrotonically remote from the soma (> 30-fold excitatory postsynaptic potential (EPSP) attenuation) and back-propagating action potentials were significantly attenuated. Unitary EPSPs were location dependent, reaching large amplitudes distally (> 8 mV), yet their somatic contribution was relatively location independent. Basal dendrites support sodium and NMDA spikes, but not calcium spikes, for 75% of their length. This suggests that basal dendrites, despite their proximity to the site of action potential initiation, do not form a single basal-somatic region but rather should be considered as a separate integrative compartment favoring two integration modes: subthreshold, location-independent summation versus local amplification of incoming spatiotemporally clustered information.