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

Inhibitory location effects: electrophysiological recordings from brain slices and detailed compartmental model.(A, C) Whole-cell somatic recording were carried out in a layer 5 pyramidal cell. Excitation was provided by UV laser uncaging of glutamate at a site 150 µm from the soma in a basal dendrite. Inhibition was delivered via GABA iontophoresis at the same site (A) or at the soma (C). Excitation was delivered at least 10 ms after the iontophoresis. Black traces show control case without inhibition, blue traces are in the presence of inhibition. (B, D) Input-output curves for peak somatic depolarization as a function of laser intensity. Spike thresholds indicated by asterisks were computed from sigmoidal fits to the i/o curves (see Methods); spike heights were computed from asymptotic values of sigmoidal fits, indicated by horizontal dashed lines. (E, G) Voltage traces at the soma generated by a detailed compartmental model of a layer-5 pyramidal cell. Excitatory synapses (NMDA+AMPA) were placed on a single basal dendrite 125 µm from the soma and inhibitory (GABAA) synapses were either co-localized with the excitation (E) or placed at the soma (G). Line colors and dashing are as in a–d. (F, H) Input-output curves for compartmental model as a function of activated excitatory synapses. 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. For the cases shown, peak inhibitory conductance was 10 nS in case of dendritic inhibition case and 90 nS in case of somatic inhibition.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3375251&req=5

pcbi-1002550-g001: Inhibitory location effects: electrophysiological recordings from brain slices and detailed compartmental model.(A, C) Whole-cell somatic recording were carried out in a layer 5 pyramidal cell. Excitation was provided by UV laser uncaging of glutamate at a site 150 µm from the soma in a basal dendrite. Inhibition was delivered via GABA iontophoresis at the same site (A) or at the soma (C). Excitation was delivered at least 10 ms after the iontophoresis. Black traces show control case without inhibition, blue traces are in the presence of inhibition. (B, D) Input-output curves for peak somatic depolarization as a function of laser intensity. Spike thresholds indicated by asterisks were computed from sigmoidal fits to the i/o curves (see Methods); spike heights were computed from asymptotic values of sigmoidal fits, indicated by horizontal dashed lines. (E, G) Voltage traces at the soma generated by a detailed compartmental model of a layer-5 pyramidal cell. Excitatory synapses (NMDA+AMPA) were placed on a single basal dendrite 125 µm from the soma and inhibitory (GABAA) synapses were either co-localized with the excitation (E) or placed at the soma (G). Line colors and dashing are as in a–d. (F, H) Input-output curves for compartmental model as a function of activated excitatory synapses. 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. For the cases shown, peak inhibitory conductance was 10 nS in case of dendritic inhibition case and 90 nS in case of somatic inhibition.

Mentions: We tested the effects of the location of inhibition in experiments in neocortical somatosensory slices. Whole cell somatic recordings were made from layer 5 pyramidal neurons. Excitation was delivered to a dendritic site ranging from 85 to 200 µm from the soma either by electrical stimulation or glutamate uncaging (Figure 1). Inhibition was applied via GABA iontophoresis either near the dendritic site of excitation (Figure 1A) or at the soma (Figure 1C). Due to the slow rate of onset of the inhibitory response (Figure S1A), the excitation (whether by glutamate uncaging or electrical stimulation) followed the GABA iontophoresis pulse by 10–200 ms (Figure S1C).


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

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

Inhibitory location effects: electrophysiological recordings from brain slices and detailed compartmental model.(A, C) Whole-cell somatic recording were carried out in a layer 5 pyramidal cell. Excitation was provided by UV laser uncaging of glutamate at a site 150 µm from the soma in a basal dendrite. Inhibition was delivered via GABA iontophoresis at the same site (A) or at the soma (C). Excitation was delivered at least 10 ms after the iontophoresis. Black traces show control case without inhibition, blue traces are in the presence of inhibition. (B, D) Input-output curves for peak somatic depolarization as a function of laser intensity. Spike thresholds indicated by asterisks were computed from sigmoidal fits to the i/o curves (see Methods); spike heights were computed from asymptotic values of sigmoidal fits, indicated by horizontal dashed lines. (E, G) Voltage traces at the soma generated by a detailed compartmental model of a layer-5 pyramidal cell. Excitatory synapses (NMDA+AMPA) were placed on a single basal dendrite 125 µm from the soma and inhibitory (GABAA) synapses were either co-localized with the excitation (E) or placed at the soma (G). Line colors and dashing are as in a–d. (F, H) Input-output curves for compartmental model as a function of activated excitatory synapses. 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. For the cases shown, peak inhibitory conductance was 10 nS in case of dendritic inhibition case and 90 nS in case of somatic inhibition.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1002550-g001: Inhibitory location effects: electrophysiological recordings from brain slices and detailed compartmental model.(A, C) Whole-cell somatic recording were carried out in a layer 5 pyramidal cell. Excitation was provided by UV laser uncaging of glutamate at a site 150 µm from the soma in a basal dendrite. Inhibition was delivered via GABA iontophoresis at the same site (A) or at the soma (C). Excitation was delivered at least 10 ms after the iontophoresis. Black traces show control case without inhibition, blue traces are in the presence of inhibition. (B, D) Input-output curves for peak somatic depolarization as a function of laser intensity. Spike thresholds indicated by asterisks were computed from sigmoidal fits to the i/o curves (see Methods); spike heights were computed from asymptotic values of sigmoidal fits, indicated by horizontal dashed lines. (E, G) Voltage traces at the soma generated by a detailed compartmental model of a layer-5 pyramidal cell. Excitatory synapses (NMDA+AMPA) were placed on a single basal dendrite 125 µm from the soma and inhibitory (GABAA) synapses were either co-localized with the excitation (E) or placed at the soma (G). Line colors and dashing are as in a–d. (F, H) Input-output curves for compartmental model as a function of activated excitatory synapses. 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. For the cases shown, peak inhibitory conductance was 10 nS in case of dendritic inhibition case and 90 nS in case of somatic inhibition.
Mentions: We tested the effects of the location of inhibition in experiments in neocortical somatosensory slices. Whole cell somatic recordings were made from layer 5 pyramidal neurons. Excitation was delivered to a dendritic site ranging from 85 to 200 µm from the soma either by electrical stimulation or glutamate uncaging (Figure 1). Inhibition was applied via GABA iontophoresis either near the dendritic site of excitation (Figure 1A) or at the soma (Figure 1C). Due to the slow rate of onset of the inhibitory response (Figure S1A), the excitation (whether by glutamate uncaging or electrical stimulation) followed the GABA iontophoresis pulse by 10–200 ms (Figure S1C).

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