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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 effects of inhibition.(A) % reduction in somatic depolarization caused by dendritic vs. somatic inhibition at stimulus levels subthreshold for NMDA spike initiation, averaged over subthreshold part of i/o curves like those shown in Figure 1 B,D. Bars shown are standard errors. (B) Scatter plot showing changes in NMDA spike threshold (x-axis) and height (y-axis) in response to dendritic (green symbols) and somatic (red symbols) inhibition, expressed as joint % change in spike height and threshold relative to no-inhibition control (black square at origin). Peak conductance for dendritic inhibition cases shown here was 10, 20, 30, and 40 nS, while that for somatic inhibition was 30, 60, 90, 120 and 150 nS. Each excitatory synapse in this experiment had 6 nS peak AMPA conductance. Excitatory synapses with 1.5 nS peak AMPA conductance with similar distribution of density along the dendrite gave similar results. The figure includes data from in vitro experiments (circles), detailed compartmental model (squares) and the reduced (2-compartment) steady state model (triangles). Open circles show the means of the respective in vitro data. Green and red shaded regions highlight the predominance of threshold elevation in cases of dendritic inhibition, and height suppression in cases of somatic inhibition.
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pcbi-1002550-g002: Summary of location effects of inhibition.(A) % reduction in somatic depolarization caused by dendritic vs. somatic inhibition at stimulus levels subthreshold for NMDA spike initiation, averaged over subthreshold part of i/o curves like those shown in Figure 1 B,D. Bars shown are standard errors. (B) Scatter plot showing changes in NMDA spike threshold (x-axis) and height (y-axis) in response to dendritic (green symbols) and somatic (red symbols) inhibition, expressed as joint % change in spike height and threshold relative to no-inhibition control (black square at origin). Peak conductance for dendritic inhibition cases shown here was 10, 20, 30, and 40 nS, while that for somatic inhibition was 30, 60, 90, 120 and 150 nS. Each excitatory synapse in this experiment had 6 nS peak AMPA conductance. Excitatory synapses with 1.5 nS peak AMPA conductance with similar distribution of density along the dendrite gave similar results. The figure includes data from in vitro experiments (circles), detailed compartmental model (squares) and the reduced (2-compartment) steady state model (triangles). Open circles show the means of the respective in vitro data. Green and red shaded regions highlight the predominance of threshold elevation in cases of dendritic inhibition, and height suppression in cases of somatic inhibition.

Mentions: To examine the effects of inhibition co-localized with the excitatory stimulus, we applied increasing levels of dendritic excitation until a local spike was evoked, both under control conditions without inhibition (Figure 1A, black traces), and paired with co-localized inhibition (Figure 1A, blue traces). Input-output curves for the traces in Figure 1A are shown in Figure 1B, plotting peak somatic voltage responses vs. stimulation intensity. For low levels of excitation that remained subthreshold for local spike generation (first 3 data points in Figure 1B), dendritic inhibition reduced somatic EPSPs by 25.8%, leading to a corresponding reduction in the initial slope of the i/o curve relative to the control condition (compare black and blue dashed lines in Figure 1B). On average across cells, initial i/o curve slopes were reduced by 19±10% compared to their pre-inhibition values (p = 0.12, Student's t-test, n = 6; Figure 2a, open green circle).


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 effects of inhibition.(A) % reduction in somatic depolarization caused by dendritic vs. somatic inhibition at stimulus levels subthreshold for NMDA spike initiation, averaged over subthreshold part of i/o curves like those shown in Figure 1 B,D. Bars shown are standard errors. (B) Scatter plot showing changes in NMDA spike threshold (x-axis) and height (y-axis) in response to dendritic (green symbols) and somatic (red symbols) inhibition, expressed as joint % change in spike height and threshold relative to no-inhibition control (black square at origin). Peak conductance for dendritic inhibition cases shown here was 10, 20, 30, and 40 nS, while that for somatic inhibition was 30, 60, 90, 120 and 150 nS. Each excitatory synapse in this experiment had 6 nS peak AMPA conductance. Excitatory synapses with 1.5 nS peak AMPA conductance with similar distribution of density along the dendrite gave similar results. The figure includes data from in vitro experiments (circles), detailed compartmental model (squares) and the reduced (2-compartment) steady state model (triangles). Open circles show the means of the respective in vitro data. Green and red shaded regions highlight the predominance of threshold elevation in cases of dendritic inhibition, and height suppression in cases of somatic inhibition.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3375251&req=5

pcbi-1002550-g002: Summary of location effects of inhibition.(A) % reduction in somatic depolarization caused by dendritic vs. somatic inhibition at stimulus levels subthreshold for NMDA spike initiation, averaged over subthreshold part of i/o curves like those shown in Figure 1 B,D. Bars shown are standard errors. (B) Scatter plot showing changes in NMDA spike threshold (x-axis) and height (y-axis) in response to dendritic (green symbols) and somatic (red symbols) inhibition, expressed as joint % change in spike height and threshold relative to no-inhibition control (black square at origin). Peak conductance for dendritic inhibition cases shown here was 10, 20, 30, and 40 nS, while that for somatic inhibition was 30, 60, 90, 120 and 150 nS. Each excitatory synapse in this experiment had 6 nS peak AMPA conductance. Excitatory synapses with 1.5 nS peak AMPA conductance with similar distribution of density along the dendrite gave similar results. The figure includes data from in vitro experiments (circles), detailed compartmental model (squares) and the reduced (2-compartment) steady state model (triangles). Open circles show the means of the respective in vitro data. Green and red shaded regions highlight the predominance of threshold elevation in cases of dendritic inhibition, and height suppression in cases of somatic inhibition.
Mentions: To examine the effects of inhibition co-localized with the excitatory stimulus, we applied increasing levels of dendritic excitation until a local spike was evoked, both under control conditions without inhibition (Figure 1A, black traces), and paired with co-localized inhibition (Figure 1A, blue traces). Input-output curves for the traces in Figure 1A are shown in Figure 1B, plotting peak somatic voltage responses vs. stimulation intensity. For low levels of excitation that remained subthreshold for local spike generation (first 3 data points in Figure 1B), dendritic inhibition reduced somatic EPSPs by 25.8%, leading to a corresponding reduction in the initial slope of the i/o curve relative to the control condition (compare black and blue dashed lines in Figure 1B). On average across cells, initial i/o curve slopes were reduced by 19±10% compared to their pre-inhibition values (p = 0.12, Student's t-test, n = 6; Figure 2a, open green circle).

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