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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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Summary of location-dependent effects of dendrite-targeting inhibition.This is expressed as joint % change in spike height and threshold relative to no-inhibition control (black square at origin). Red and green shaded areas were carried over from Figure 2 to indicate general trends for dendritic vs. somatic inhibition. In vitro data (red and green circles) were collected from different dendrites at different distal or on-the-path locations; separation distances between excitation and site of GABA iontophoresis are indicated in figure next to each data point. Results from detailed compartmental model are shown to provide context, including one representative location of more distal inhibition (open green squares) and three locations of on-the-path inhibition (open orange squares). Iso-inhibition and iso-location lines are splines fitted to the data points from the detailed compartmental model. Co-localized (filled green squares) and somatic (filled red squares) inhibition locations are shown for reference. In case of data points from the detailed compartmental model, size is indicative of strength. Simulations were carried out on an un-branched dendrite, though the results were similar for other dendrites.
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pcbi-1002550-g007: Summary of location-dependent effects of dendrite-targeting inhibition.This is expressed as joint % change in spike height and threshold relative to no-inhibition control (black square at origin). Red and green shaded areas were carried over from Figure 2 to indicate general trends for dendritic vs. somatic inhibition. In vitro data (red and green circles) were collected from different dendrites at different distal or on-the-path locations; separation distances between excitation and site of GABA iontophoresis are indicated in figure next to each data point. Results from detailed compartmental model are shown to provide context, including one representative location of more distal inhibition (open green squares) and three locations of on-the-path inhibition (open orange squares). Iso-inhibition and iso-location lines are splines fitted to the data points from the detailed compartmental model. Co-localized (filled green squares) and somatic (filled red squares) inhibition locations are shown for reference. In case of data points from the detailed compartmental model, size is indicative of strength. Simulations were carried out on an un-branched dendrite, though the results were similar for other dendrites.

Mentions: In contrast, when inhibition was activated on the path between the excitation and the soma, we observed a mixture of somatic and dendritic effects (Figure 6B), that is, the inhibition significantly affected both the NMDA spike threshold and height. While it was not possible to make strict quantitative comparisons between model and data given that the data was collected from cells with different dendritic morphologies and excitation occurred at different distances from the soma, in both cases the relative amounts of gain vs. threshold inhibition depended systematically on the separation of on-the-path inhibition from the site of excitation (Figure 7, orange circles). Inhibition closer to the site of excitation mainly increased the threshold for NMDA spike generation (e.g. orange circle labeled −20 µm), whereas at larger separations, when inhibition moved closer to the soma, it mainly suppressed spike height (e.g. orange circle labeled −70 µm).


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

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

Summary of location-dependent effects of dendrite-targeting inhibition.This is expressed as joint % change in spike height and threshold relative to no-inhibition control (black square at origin). Red and green shaded areas were carried over from Figure 2 to indicate general trends for dendritic vs. somatic inhibition. In vitro data (red and green circles) were collected from different dendrites at different distal or on-the-path locations; separation distances between excitation and site of GABA iontophoresis are indicated in figure next to each data point. Results from detailed compartmental model are shown to provide context, including one representative location of more distal inhibition (open green squares) and three locations of on-the-path inhibition (open orange squares). Iso-inhibition and iso-location lines are splines fitted to the data points from the detailed compartmental model. Co-localized (filled green squares) and somatic (filled red squares) inhibition locations are shown for reference. In case of data points from the detailed compartmental model, size is indicative of strength. Simulations were carried out on an un-branched dendrite, though the results were similar for other dendrites.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3375251&req=5

pcbi-1002550-g007: Summary of location-dependent effects of dendrite-targeting inhibition.This is expressed as joint % change in spike height and threshold relative to no-inhibition control (black square at origin). Red and green shaded areas were carried over from Figure 2 to indicate general trends for dendritic vs. somatic inhibition. In vitro data (red and green circles) were collected from different dendrites at different distal or on-the-path locations; separation distances between excitation and site of GABA iontophoresis are indicated in figure next to each data point. Results from detailed compartmental model are shown to provide context, including one representative location of more distal inhibition (open green squares) and three locations of on-the-path inhibition (open orange squares). Iso-inhibition and iso-location lines are splines fitted to the data points from the detailed compartmental model. Co-localized (filled green squares) and somatic (filled red squares) inhibition locations are shown for reference. In case of data points from the detailed compartmental model, size is indicative of strength. Simulations were carried out on an un-branched dendrite, though the results were similar for other dendrites.
Mentions: In contrast, when inhibition was activated on the path between the excitation and the soma, we observed a mixture of somatic and dendritic effects (Figure 6B), that is, the inhibition significantly affected both the NMDA spike threshold and height. While it was not possible to make strict quantitative comparisons between model and data given that the data was collected from cells with different dendritic morphologies and excitation occurred at different distances from the soma, in both cases the relative amounts of gain vs. threshold inhibition depended systematically on the separation of on-the-path inhibition from the site of excitation (Figure 7, orange circles). Inhibition closer to the site of excitation mainly increased the threshold for NMDA spike generation (e.g. orange circle labeled −20 µm), whereas at larger separations, when inhibition moved closer to the soma, it mainly suppressed spike height (e.g. orange circle labeled −70 µm).

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
Related in: MedlinePlus