Limits...
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.

Show MeSH

Related in: MedlinePlus

Mechanisms underlying stereotypical NMDA spike height.(A) A single voltage compartment containing NMDA and leak conductances. (B) I–V curves for two levels of leak and threshold NMDA conductances for the circuit shown in A. Increasing leak scales the leak I–V curve (shown in green, sign reversed and reflected below the x-axis). Levels of NMDA conductance shown (red I–V curves) correspond to two different values of channels Nsyn in equation 1 and were just suprathreshold for NMDA spike generation in control and increased leak cases. Spike heights are same in two cases (black and blue dashed arrows). (C) Equivalent circuits from perspective of dendritic compartment (node s) for cases with no inhibition (c1), with dendritic inhibition (c2) or with somatic inhibition (c3), (EL = EI). Shaded grey areas indicate all conductances contributing to total leak from the perspective of the dendritic compartment.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3375251&req=5

pcbi-1002550-g005: Mechanisms underlying stereotypical NMDA spike height.(A) A single voltage compartment containing NMDA and leak conductances. (B) I–V curves for two levels of leak and threshold NMDA conductances for the circuit shown in A. Increasing leak scales the leak I–V curve (shown in green, sign reversed and reflected below the x-axis). Levels of NMDA conductance shown (red I–V curves) correspond to two different values of channels Nsyn in equation 1 and were just suprathreshold for NMDA spike generation in control and increased leak cases. Spike heights are same in two cases (black and blue dashed arrows). (C) Equivalent circuits from perspective of dendritic compartment (node s) for cases with no inhibition (c1), with dendritic inhibition (c2) or with somatic inhibition (c3), (EL = EI). Shaded grey areas indicate all conductances contributing to total leak from the perspective of the dendritic compartment.

Mentions: Details. In a single electrical compartment (Figure 5A), increasing the total leak conductance by activating shunting inhibition produces a multiplicative scaling of the leak I–V curve – compare 2 green curves in Figure 5B. To generate an NMDA spike in the presence of an increased total leak, an original just-suprathreshold NMDA conductance (see Figure S3E) must be scaled up by the same factor as the increase in total leak conductance to re-obtain the threshold condition (see 2 red curves representing NMDA I–V curves skimming just below two green curves in Figure 5B). Importantly, under this co-scaling of NMDA and total leak conductances, the voltage at the intersection of the NMDA and leak I–V curves (red dots) remains unchanged, which predicts a constant NMDA spike height regardless of the level of inhibition (see Text S1 for further explanation).


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

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

Mechanisms underlying stereotypical NMDA spike height.(A) A single voltage compartment containing NMDA and leak conductances. (B) I–V curves for two levels of leak and threshold NMDA conductances for the circuit shown in A. Increasing leak scales the leak I–V curve (shown in green, sign reversed and reflected below the x-axis). Levels of NMDA conductance shown (red I–V curves) correspond to two different values of channels Nsyn in equation 1 and were just suprathreshold for NMDA spike generation in control and increased leak cases. Spike heights are same in two cases (black and blue dashed arrows). (C) Equivalent circuits from perspective of dendritic compartment (node s) for cases with no inhibition (c1), with dendritic inhibition (c2) or with somatic inhibition (c3), (EL = EI). Shaded grey areas indicate all conductances contributing to total leak from the perspective of the dendritic compartment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375251&req=5

pcbi-1002550-g005: Mechanisms underlying stereotypical NMDA spike height.(A) A single voltage compartment containing NMDA and leak conductances. (B) I–V curves for two levels of leak and threshold NMDA conductances for the circuit shown in A. Increasing leak scales the leak I–V curve (shown in green, sign reversed and reflected below the x-axis). Levels of NMDA conductance shown (red I–V curves) correspond to two different values of channels Nsyn in equation 1 and were just suprathreshold for NMDA spike generation in control and increased leak cases. Spike heights are same in two cases (black and blue dashed arrows). (C) Equivalent circuits from perspective of dendritic compartment (node s) for cases with no inhibition (c1), with dendritic inhibition (c2) or with somatic inhibition (c3), (EL = EI). Shaded grey areas indicate all conductances contributing to total leak from the perspective of the dendritic compartment.
Mentions: Details. In a single electrical compartment (Figure 5A), increasing the total leak conductance by activating shunting inhibition produces a multiplicative scaling of the leak I–V curve – compare 2 green curves in Figure 5B. To generate an NMDA spike in the presence of an increased total leak, an original just-suprathreshold NMDA conductance (see Figure S3E) must be scaled up by the same factor as the increase in total leak conductance to re-obtain the threshold condition (see 2 red curves representing NMDA I–V curves skimming just below two green curves in Figure 5B). Importantly, under this co-scaling of NMDA and total leak conductances, the voltage at the intersection of the NMDA and leak I–V curves (red dots) remains unchanged, which predicts a constant NMDA spike height regardless of the level of inhibition (see Text S1 for further explanation).

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