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Location-dependent effects of inhibition on local spiking in pyramidal neuron dendrites.

Jadi M, Polsky A, Schiller J, Mel BW - PLoS Comput. Biol. (2012)

Bottom Line: A key feature distinguishing interneuron types is the spatial distribution of their synaptic contacts onto PNs, but the location-dependent effects of inhibition are mostly unknown, especially under conditions involving active dendritic responses.We studied the effect of somatic vs. dendritic inhibition on local spike generation in basal dendrites of layer 5 PNs both in neocortical slices and in simple and detailed compartmental models, with equivalent results: somatic inhibition divisively suppressed the amplitude of dendritic spikes recorded at the soma while minimally affecting dendritic spike thresholds.Our findings suggest that cortical circuits could assign different mixtures of gain vs. threshold inhibition to different neural pathways, and thus tailor their local computations, by managing their relative activation of soma- vs. dendrite-targeting interneurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, California, United States of America. jadi@salk.edu

ABSTRACT
Cortical computations are critically dependent on interactions between pyramidal neurons (PNs) and a menagerie of inhibitory interneuron types. A key feature distinguishing interneuron types is the spatial distribution of their synaptic contacts onto PNs, but the location-dependent effects of inhibition are mostly unknown, especially under conditions involving active dendritic responses. We studied the effect of somatic vs. dendritic inhibition on local spike generation in basal dendrites of layer 5 PNs both in neocortical slices and in simple and detailed compartmental models, with equivalent results: somatic inhibition divisively suppressed the amplitude of dendritic spikes recorded at the soma while minimally affecting dendritic spike thresholds. In contrast, distal dendritic inhibition raised dendritic spike thresholds while minimally affecting their amplitudes. On-the-path dendritic inhibition modulated both the gain and threshold of dendritic spikes depending on its distance from the spike initiation zone. Our findings suggest that cortical circuits could assign different mixtures of gain vs. threshold inhibition to different neural pathways, and thus tailor their local computations, by managing their relative activation of soma- vs. dendrite-targeting interneurons.

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Dendritic spike height is not affected by somatic inhibition.(A) Experimental setup for testing somatic inhibition. Red electrode shows dendritic site of stimulation, blue electrode shows somatic site of GABA iontophoresis. (B) Voltage traces (top) and dendritic calcium signal (bottom) for control case (black) and with somatic inhibition (blue). (C) Bar plots compare dendritic calcium signal peaks (control: black, GABA: blue) for EPSPs that were both subthreshold and suprathreshold to NMDA spikes. (D) Morphology and stimulation set up in detailed compartmental model. Red square indicates location of excitatory synapses on a single dendrite, while the blue square indicates somatic location of inhibitory synapses. (E) Membrane potential at the soma and dendritic location for increasing levels of excitation (6 nS per synapse). Black traces indicate control, while blue traces indicate co-stimulation of somatic inhibitory synapses (peak conductance = 90 nS). (F) I/O curves at the soma and at the dendritic location for peak Vm for control (black) and somatic inhibition (blue).
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pcbi-1002550-g003: Dendritic spike height is not affected by somatic inhibition.(A) Experimental setup for testing somatic inhibition. Red electrode shows dendritic site of stimulation, blue electrode shows somatic site of GABA iontophoresis. (B) Voltage traces (top) and dendritic calcium signal (bottom) for control case (black) and with somatic inhibition (blue). (C) Bar plots compare dendritic calcium signal peaks (control: black, GABA: blue) for EPSPs that were both subthreshold and suprathreshold to NMDA spikes. (D) Morphology and stimulation set up in detailed compartmental model. Red square indicates location of excitatory synapses on a single dendrite, while the blue square indicates somatic location of inhibitory synapses. (E) Membrane potential at the soma and dendritic location for increasing levels of excitation (6 nS per synapse). Black traces indicate control, while blue traces indicate co-stimulation of somatic inhibitory synapses (peak conductance = 90 nS). (F) I/O curves at the soma and at the dendritic location for peak Vm for control (black) and somatic inhibition (blue).

Mentions: A key difference between dendritic and somatic inhibition conditions was the observation of full-height spikes at the soma under increasing levels of dendritic inhibition, in contrast to a gradual reduction in the peak response at the soma under increasing levels of somatic inhibition (Figure 2). The graded suppression of peak responses at the soma by somatic inhibition could have been due to a gradual suppression of peak responses at the distal site of spike generation, reflecting a gradual weakening of NMDA current regenerativity. Alternatively, the dendritic spike could have remained constant in height locally in the dendrite, with the suppression explained by a greater attenuation of the voltage signal transferred from the dendrite to the soma. To distinguish these cases, we performed simultaneous voltage recordings at the soma and calcium imaging in the activated dendrite, measuring peak calcium transients with the indicator OGB-1 (Figure 3A). Calcium transients in the presence and absence of somatic inhibition were indistinguishable (control: 120±57%, GABA: 105±46%; non-significant with ANOVA), and significantly higher than those associated with just-subthreshold levels of excitation (p<0.01, Figure 3B,C), suggesting that the regenerative capacity at the dendritic site was unaltered by the presence of somatic inhibition (Figure 3B,C). Given uncertainties in the interpretation of calcium transients as surrogates for membrane potential, however, we directly measured dendritic voltages in compartmental simulations under comparable experimental conditions (Figure 3D,E). Consistent with the lack of change in the calcium transients seen in the experiments, dendritic spike heights in the model were also virtually unchanged by somatic inhibition, despite the substantial spike height reduction measured at the soma (Figure 3E,F). Thus, the experimental and modeling data were both consistent with invariant spike height for either location of inhibition.


Location-dependent effects of inhibition on local spiking in pyramidal neuron dendrites.

Jadi M, Polsky A, Schiller J, Mel BW - PLoS Comput. Biol. (2012)

Dendritic spike height is not affected by somatic inhibition.(A) Experimental setup for testing somatic inhibition. Red electrode shows dendritic site of stimulation, blue electrode shows somatic site of GABA iontophoresis. (B) Voltage traces (top) and dendritic calcium signal (bottom) for control case (black) and with somatic inhibition (blue). (C) Bar plots compare dendritic calcium signal peaks (control: black, GABA: blue) for EPSPs that were both subthreshold and suprathreshold to NMDA spikes. (D) Morphology and stimulation set up in detailed compartmental model. Red square indicates location of excitatory synapses on a single dendrite, while the blue square indicates somatic location of inhibitory synapses. (E) Membrane potential at the soma and dendritic location for increasing levels of excitation (6 nS per synapse). Black traces indicate control, while blue traces indicate co-stimulation of somatic inhibitory synapses (peak conductance = 90 nS). (F) I/O curves at the soma and at the dendritic location for peak Vm for control (black) and somatic inhibition (blue).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3375251&req=5

pcbi-1002550-g003: Dendritic spike height is not affected by somatic inhibition.(A) Experimental setup for testing somatic inhibition. Red electrode shows dendritic site of stimulation, blue electrode shows somatic site of GABA iontophoresis. (B) Voltage traces (top) and dendritic calcium signal (bottom) for control case (black) and with somatic inhibition (blue). (C) Bar plots compare dendritic calcium signal peaks (control: black, GABA: blue) for EPSPs that were both subthreshold and suprathreshold to NMDA spikes. (D) Morphology and stimulation set up in detailed compartmental model. Red square indicates location of excitatory synapses on a single dendrite, while the blue square indicates somatic location of inhibitory synapses. (E) Membrane potential at the soma and dendritic location for increasing levels of excitation (6 nS per synapse). Black traces indicate control, while blue traces indicate co-stimulation of somatic inhibitory synapses (peak conductance = 90 nS). (F) I/O curves at the soma and at the dendritic location for peak Vm for control (black) and somatic inhibition (blue).
Mentions: A key difference between dendritic and somatic inhibition conditions was the observation of full-height spikes at the soma under increasing levels of dendritic inhibition, in contrast to a gradual reduction in the peak response at the soma under increasing levels of somatic inhibition (Figure 2). The graded suppression of peak responses at the soma by somatic inhibition could have been due to a gradual suppression of peak responses at the distal site of spike generation, reflecting a gradual weakening of NMDA current regenerativity. Alternatively, the dendritic spike could have remained constant in height locally in the dendrite, with the suppression explained by a greater attenuation of the voltage signal transferred from the dendrite to the soma. To distinguish these cases, we performed simultaneous voltage recordings at the soma and calcium imaging in the activated dendrite, measuring peak calcium transients with the indicator OGB-1 (Figure 3A). Calcium transients in the presence and absence of somatic inhibition were indistinguishable (control: 120±57%, GABA: 105±46%; non-significant with ANOVA), and significantly higher than those associated with just-subthreshold levels of excitation (p<0.01, Figure 3B,C), suggesting that the regenerative capacity at the dendritic site was unaltered by the presence of somatic inhibition (Figure 3B,C). Given uncertainties in the interpretation of calcium transients as surrogates for membrane potential, however, we directly measured dendritic voltages in compartmental simulations under comparable experimental conditions (Figure 3D,E). Consistent with the lack of change in the calcium transients seen in the experiments, dendritic spike heights in the model were also virtually unchanged by somatic inhibition, despite the substantial spike height reduction measured at the soma (Figure 3E,F). Thus, the experimental and modeling data were both consistent with invariant spike height for either location of inhibition.

Bottom Line: A key feature distinguishing interneuron types is the spatial distribution of their synaptic contacts onto PNs, but the location-dependent effects of inhibition are mostly unknown, especially under conditions involving active dendritic responses.We studied the effect of somatic vs. dendritic inhibition on local spike generation in basal dendrites of layer 5 PNs both in neocortical slices and in simple and detailed compartmental models, with equivalent results: somatic inhibition divisively suppressed the amplitude of dendritic spikes recorded at the soma while minimally affecting dendritic spike thresholds.Our findings suggest that cortical circuits could assign different mixtures of gain vs. threshold inhibition to different neural pathways, and thus tailor their local computations, by managing their relative activation of soma- vs. dendrite-targeting interneurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, California, United States of America. jadi@salk.edu

ABSTRACT
Cortical computations are critically dependent on interactions between pyramidal neurons (PNs) and a menagerie of inhibitory interneuron types. A key feature distinguishing interneuron types is the spatial distribution of their synaptic contacts onto PNs, but the location-dependent effects of inhibition are mostly unknown, especially under conditions involving active dendritic responses. We studied the effect of somatic vs. dendritic inhibition on local spike generation in basal dendrites of layer 5 PNs both in neocortical slices and in simple and detailed compartmental models, with equivalent results: somatic inhibition divisively suppressed the amplitude of dendritic spikes recorded at the soma while minimally affecting dendritic spike thresholds. In contrast, distal dendritic inhibition raised dendritic spike thresholds while minimally affecting their amplitudes. On-the-path dendritic inhibition modulated both the gain and threshold of dendritic spikes depending on its distance from the spike initiation zone. Our findings suggest that cortical circuits could assign different mixtures of gain vs. threshold inhibition to different neural pathways, and thus tailor their local computations, by managing their relative activation of soma- vs. dendrite-targeting interneurons.

Show MeSH