Signal propagation in oblique dendrites of CA1 pyramidal cells

Abstract

The electrophysiological properties of the oblique branches of CA1 pyramidal neurons are largely unknown and very difficult to investigate experimentally. These relatively thin dendrites make up the majority of the apical tree surface area and constitute the main target of Schaffer collateral axons from CA3. Their electrogenic properties might have an important role in defining the computational functions of CA1 neurons. It is thus important to determine if and to what extent the back- and forward propagation of action potentials (AP) in these dendrites could be modulated by local properties such as morphology or active conductances. In the first detailed study of signal propagation in the full extent of CA1 oblique dendrites, we used 27 reconstructed three-dimensional morphologies and different distributions of the A-type K(+) conductance (K(A)), to investigate their electrophysiological properties by computational modeling. We found that the local K(A) distribution had a major role in modulating action potential back propagation, whereas the forward propagation of dendritic spikes originating in the obliques was mainly affected by local morphological properties. In both cases, signal processing in any given oblique was effectively independent of the rest of the neuron and, by and large, of the distance from the soma. Moreover, the density of K(A) in oblique dendrites affected spike conduction in the main shaft. Thus the anatomical variability of CA1 pyramidal cells and their local distribution of voltage-gated channels may suit a powerful functional compartmentalization of the apical tree.

FIG. 1

Definition and basic properties of the CA1 pyramidal cell models. A: 2-dimensional projections of the digital morphological reconstructions of neurons C91662 and n400 (oblique trees are shown in gray). B: input resistance, R_N, of all the neurons used in the simulations (shown for the LI model); the vertical dotted line separates values for reconstructions of neurons from adult (left) and young (right) animals.

FIG. 2

Depolarization of oblique branches caused by a back-propagating action potential (AP). A, left: schematic representation of the typical simulation setup: AP back propagation was studied by eliciting a somatic AP with a short somatic current pulse. The plot shows the peak AP amplitude along the trunk (closed symbols) and each oblique (open symbols) for neuron 5038804 (type LI). Inset: the somatic membrane potential. B: distribution of the average peak depolarization of each oblique branch, <peak_obl>, using different K_A distributions. C: <peak_obl> as a function of the ratio between the diameter of the oblique and of the parent trunk at the branch point. D: <peak_obl> as a function of the oblique surface area. B–D show results for all neurons (open circles, type C1; closed triangles, type C3; the type LI yields similar, intermediate results, not shown for graphical clarity).

FIG. 3

Selective control of antidromic AP invasion of an oblique branch. A: average peak depolarization of each oblique branch, <peak_obl>, during the back propagation of a somatic AP using C1 and C3 distributions, as a function of the path distance between the oblique stem on the main trunk and the soma (each symbol represents 1 oblique). B: peak AP amplitude in neuron C81462 with a type C1 distribution as a function of distance from the soma (the 2 trunks correspond to a “main” bifurcation of the apical tree); △, trunk; ●, obliques. C: analogous simulation of the same neuron as in B, but with a type C3 distribution in ≈30% of the obliques (○, oblique trees with a C3 distribution). D: effects of a local depolarization of 4 mV ( ) or 8 mV (●) on AP back propagation into an oblique with a C3 distribution; the arrow marks the location of a local depolarizing current step of 0.005 nA (4 mV) or 0.01 nA (8 mV); the neuron and channels distribution were the same as in C); for clarity, only the oblique used for the current injection and the apical trunk to which it is attached are shown.

FIG. 4

A: peak AP amplitude in the trunk during back propagation as a function of distance from soma for C1 and C3 distributions. All neurons are included, and each symbol represents a different location along the apical trunks. B: peak AP amplitude in the trunk during back propagation as a function of distance from soma for neuron C81462 using C1 (circles) and C3 (triangles) distributions with or without (gray symbols) I_h. C and D: average (±SD) peak AP amplitude in the trunk during back propagation as a function of distance from soma (50-μm bins) for neurons from young (C) or adult (D) animals using C1 (black bars) and C3 (gray bars) distributions.

FIG. 5

Forward propagation of an AP elicited in an oblique. A, left: schematic representation of the typical simulation setup: forward propagation was studied by eliciting a single dendritic AP with a suprathreshold synaptic stimulation. The plot shows the peak AP amplitude along the trunk (●) and each oblique (○), for neuron 5038804 (type LI). Inset: the dendritic membrane potential of a particular stimulation site (indicated marker, ~180 μm from soma). B: average peak depolarization of each oblique branch, <peak_obl>, using different K_A distributions, as a function of the path distance between the oblique stem on the main trunk and the soma (each symbol represents 1 oblique). C: average peak amplitude reached in the main trunk at the branch point with the stimulated oblique tree.

FIG. 6

The ratio between the peak membrane potential in the oblique and that reached in the trunk at the branch point following a dendritic AP, peak ratio, as a measure of forward propagation (data for LI distribution). A: peak ratio as a function of distance from the soma for obliques stemming out of the apical trunk at 0–50 μm (black symbols), 200–250 μm (white symbols), and 350 – 400 μm (gray symbols) from the soma; for clarity, 3rd-order branches are not shown. For each region, the compartments of 3 obliques from different neurons are highlighted in blue, red, and green for varying ratios between the diameter of the oblique and the diameter of the trunk at the branch point, D_obl/D_trunk (reported in the insets above each region). B: peak ratio along all obliques compartments as a function of their diameter and distance from the branch point. C: peak ratio for obliques dendrites with diameter ~0.3–0.4 μm, as a function of D_obl/D_trunk and distance from the branch point on the trunk.

FIG. 7

Relative ability of oblique dendrites to transmit a local spike to the soma. A: schematic representation of a typical simulation setup: a single dendritic AP was elicited in the presence of a constant depolarizing current injection at the branch point in the trunk. B: proportion of oblique trees (total n = 664) for which a somatic spike could be elicited without additional stimulation of the trunk (always), those for which a somatic spike could be elicited only in the presence of additional subthreshold stimulation of the trunk (sometimes), and those for which a somatic spike could not be elicited with any additional subthreshold stimulation of the trunk (never). Results for the different K_A distributions types (LI, C1, and C3) are shown in different panels; sampling of 50 μm were used ≤500 μm, with oblique trees at 500 – 800 μm from soma (n = 8) grouped together. The total number of trees at each value is shown in the top panel. C: average (±SD) value of the (subthreshold) current injection in the trunk necessary to elicit a somatic spike during supra-threshold stimulation of an oblique tree in the sometimes group using different K_A distributions.

FIG. 8

Influence of oblique tree surface area on the propagation of oblique spikes to the soma (data for LI distribution; qualitatively similar results were obtained for the C1 and C3 distributions). A: proportion of trees in the always, sometimes, and never categories as a function of the oblique surface area (numbers of trees at each abscissa value are reported on the top horizontal axis). B: average trunk current injection (blue, left axis) and resulting voltage depolarization (red, right axis) necessary to elicit a somatic spike during a local supra-threshold stimulation of sometimes oblique trees. Averages (±SD) over all oblique trees of the mean values among all compartments of each tree are plotted. C: average diameter (±SD) of the sometimes oblique trees as a function of their surface area. D: diameters distribution of the sometimes oblique trees.