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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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Effect of dendritic inhibition depends on location relative to excitation.(A,B) Voltage traces and i/o curves for whole-cell somatic recordings in vitro. In A, uncaging site was 75 µm from the soma while inhibition was 120 µm from the soma. Sites of excitation and inhibition were reversed in B. Excitation was delivered at least 10 ms after the iontophoresis. (C,D) I/O curves from the detailed compartmental model. Excitatory synapses (containing NMDA+AMPA conductance) were placed on a basal dendrite 125 µm from the soma. Inhibitory synapses (GABAA) were placed either 80 µm more distal than the excitation (C) or 80 µm more proximal, i.e. on-the-path to the soma (D). The red and blue rectangles in the C and D insets illustrate the spread of E and I types of synapses at their respective locations on the dendrite. The synapses were placed 0.5 µm apart as illustrated in Figure 1. Same number of GABAA- type synapses were activated in C,D. Each excitatory synapse in the simulations had 6 nS peak AMPA conductance. For the cases shown, peak inhibitory conductance was 20 nS.
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pcbi-1002550-g006: Effect of dendritic inhibition depends on location relative to excitation.(A,B) Voltage traces and i/o curves for whole-cell somatic recordings in vitro. In A, uncaging site was 75 µm from the soma while inhibition was 120 µm from the soma. Sites of excitation and inhibition were reversed in B. Excitation was delivered at least 10 ms after the iontophoresis. (C,D) I/O curves from the detailed compartmental model. Excitatory synapses (containing NMDA+AMPA conductance) were placed on a basal dendrite 125 µm from the soma. Inhibitory synapses (GABAA) were placed either 80 µm more distal than the excitation (C) or 80 µm more proximal, i.e. on-the-path to the soma (D). The red and blue rectangles in the C and D insets illustrate the spread of E and I types of synapses at their respective locations on the dendrite. The synapses were placed 0.5 µm apart as illustrated in Figure 1. Same number of GABAA- type synapses were activated in C,D. Each excitatory synapse in the simulations had 6 nS peak AMPA conductance. For the cases shown, peak inhibitory conductance was 20 nS.

Mentions: Having established a clear dichotomy between somatic inhibition and dendritic inhibition co-localized with the excitatory stimulus, we carried out additional experiments to explore the effects of dendritic inhibition when the inhibition was either more distal than the excitation, or more proximal, that is, on the path to the soma. When inhibition was more distal than the site of glutamate uncaging (Figure 6A), the interaction closely resembled the co-localized case (see Figure 1B,F). Distal inhibition reduced the amplitude of the subthreshold EPSP by 48±7% (p = 0.006, paired Student's test, n = 4). However, despite this subthreshold shunting and the substantial increase in stimulus intensity needed to reach spike threshold (249±45%; p = 0.05, paired Student's test, n = 4,), NMDA spike height at the soma was again nearly unchanged (92±3% of control; p = 0.23, Student's t-test, n = 4).


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

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

Effect of dendritic inhibition depends on location relative to excitation.(A,B) Voltage traces and i/o curves for whole-cell somatic recordings in vitro. In A, uncaging site was 75 µm from the soma while inhibition was 120 µm from the soma. Sites of excitation and inhibition were reversed in B. Excitation was delivered at least 10 ms after the iontophoresis. (C,D) I/O curves from the detailed compartmental model. Excitatory synapses (containing NMDA+AMPA conductance) were placed on a basal dendrite 125 µm from the soma. Inhibitory synapses (GABAA) were placed either 80 µm more distal than the excitation (C) or 80 µm more proximal, i.e. on-the-path to the soma (D). The red and blue rectangles in the C and D insets illustrate the spread of E and I types of synapses at their respective locations on the dendrite. The synapses were placed 0.5 µm apart as illustrated in Figure 1. Same number of GABAA- type synapses were activated in C,D. Each excitatory synapse in the simulations had 6 nS peak AMPA conductance. For the cases shown, peak inhibitory conductance was 20 nS.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3375251&req=5

pcbi-1002550-g006: Effect of dendritic inhibition depends on location relative to excitation.(A,B) Voltage traces and i/o curves for whole-cell somatic recordings in vitro. In A, uncaging site was 75 µm from the soma while inhibition was 120 µm from the soma. Sites of excitation and inhibition were reversed in B. Excitation was delivered at least 10 ms after the iontophoresis. (C,D) I/O curves from the detailed compartmental model. Excitatory synapses (containing NMDA+AMPA conductance) were placed on a basal dendrite 125 µm from the soma. Inhibitory synapses (GABAA) were placed either 80 µm more distal than the excitation (C) or 80 µm more proximal, i.e. on-the-path to the soma (D). The red and blue rectangles in the C and D insets illustrate the spread of E and I types of synapses at their respective locations on the dendrite. The synapses were placed 0.5 µm apart as illustrated in Figure 1. Same number of GABAA- type synapses were activated in C,D. Each excitatory synapse in the simulations had 6 nS peak AMPA conductance. For the cases shown, peak inhibitory conductance was 20 nS.
Mentions: Having established a clear dichotomy between somatic inhibition and dendritic inhibition co-localized with the excitatory stimulus, we carried out additional experiments to explore the effects of dendritic inhibition when the inhibition was either more distal than the excitation, or more proximal, that is, on the path to the soma. When inhibition was more distal than the site of glutamate uncaging (Figure 6A), the interaction closely resembled the co-localized case (see Figure 1B,F). Distal inhibition reduced the amplitude of the subthreshold EPSP by 48±7% (p = 0.006, paired Student's test, n = 4). However, despite this subthreshold shunting and the substantial increase in stimulus intensity needed to reach spike threshold (249±45%; p = 0.05, paired Student's test, n = 4,), NMDA spike height at the soma was again nearly unchanged (92±3% of control; p = 0.23, Student's t-test, n = 4).

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