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Comparative Study
. 2007 Jul 3;104(27):11447-52.
doi: 10.1073/pnas.0701586104. Epub 2007 Jun 25.

Targeted dendrotomy reveals active and passive contributions of the dendritic tree to synaptic integration and neuronal output

John M Bekkers  1 , Michael Häusser
Affiliations
Comparative Study

Targeted dendrotomy reveals active and passive contributions of the dendritic tree to synaptic integration and neuronal output

John M Bekkers et al. Proc Natl Acad Sci U S A. .

Abstract

Neurons typically function as transduction devices, converting patterns of synaptic inputs, received on the dendrites, into trains of output action potentials in the axon. This transduction process is surprisingly complex and has been proposed to involve a two-way dialogue between axosomatic and dendritic compartments that can generate mutually interacting regenerative responses. To manipulate this process, we have developed a new approach for rapid and reversible occlusion or amputation of the primary dendrites of individual neurons in brain slices. By applying these techniques to cerebellar Purkinje and layer 5 cortical pyramidal neurons, we show directly that both the active and passive properties of dendrites differentially affect firing in the axon depending on the strength of stimulation. For weak excitation, dendrites act as a passive electrical load, raising spike threshold and dampening axonal excitability. For strong excitation, dendrites contribute regenerative inward currents, which trigger burst firing and enhance neuronal excitability. These findings provide direct support for the idea that dendritic morphology and conductances act in concert to regulate the excitability of the neuron.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Dendrotomy of a cerebellar Purkinje cell. (A) (Left) Biocytin-filled rat cerebellar Purkinje cell showing the dendritic tree attached to the soma by a single apical trunk. (Right) Infrared image of a different Purkinje cell (P19) during somatic whole-cell recording. The two pincer pipettes (arrows) are visible in their starting positions before dendrotomy. (B) Monitoring the progress of the dendrotomy (same cell as A Right). (Ba) (Left) Responses to a 5-mV hyperpolarizing voltage-clamp step before (control) and after (dendrotomy) amputation. (Right) Input resistance calculated from the step response plotted against time. The heavy dashed line indicates the period when the lower pincer was being raised. In this experiment, the apparent total capacitance of the cell decreased from 585.7 pF (before dendrotomy) to 21.9 pF (after dendrotomy). (Bb) (Left) Before and after responses to a 30-mV hyperpolarizing voltage-clamp step in the same cell, activating Ih. (Right) Time course plot showing the decline in Ih with dendrotomy. (Bc) (Left) Before and after responses to stimulation of parallel fiber inputs onto the distal dendrites. (Right) Time course plot showing the loss of synaptic input to the dendrites during dendrotomy. (C) (Left) Time course plot showing reversible pinching in a different Purkinje cell. Heavy dashed lines indicate the times during which the lower pincer was raised (≈1–9 min) and then lowered (≈44–51 min). Filled squares indicate the values of Rin and Ih measured 6 min before time 0 on the abscissa, confirming stability. Large filled circles indicate the values of Rin and Ih at time 39 min, during the period the pincers were stationary (≈9–44 min). (Right) Example traces at the numbered time points.
Fig. 2.
Fig. 2.
Dendrotomy and pinching of the dendritic tree alter the properties of APs in Purkinje cells and large layer 5 cortical pyramidal cells. (Aa) APs evoked by step depolarization in a Purkinje cell before (black) and after (red) dendritic amputation. (Ab) The first AP in the trains in a shown superimposed and expanded. (Ac) Summary of changes in AP voltage threshold (bar 1), AP height (bar 2), and AHP amplitude (bar 3) after dendrotomy of Purkinje cells (n = 6). (Ba) APs measured in a Purkinje cell before (black), during (red), and after (blue) pinching the dendritic trunk. (Bb) Summary of changes in AP threshold, AP height, and AHP amplitude during (red bars, n = 18) and after (blue bars, n = 3) pinching, all compared to values measured in the same cell before pinching. (Ca) APs evoked by step depolarization in a large layer 5 cortical pyramidal neuron before and during dendritic pinching. (Cb) The first AP from the trains in a superimposed and expanded. (Cc) Summary of changes in AP threshold, AP height, and AHP amplitude after pinching of layer 5 cells (n = 16).
Fig. 3.
Fig. 3.
Pinching alters input–output relationships, and a compartmental model qualitatively replicates all effects of pinching. (A) APs evoked by a series of step current injections (values above the traces) applied to a Purkinje cell before (black) and during (red) dendritic pinching. (B) f-I plot for the Purkinje cell in A before and during pinching. (C) (Top Left) Purkinje cell used in the modeling. (Top Right) Calculated single AP in this cell before (black) and during (red) simulated pinching. (Middle and Bottom) Trains of simulated APs in response to current steps before and during pinching. (D) f-I plots calculated from simulations like those in C.
Fig. 4.
Fig. 4.
Dendrotomy abolishes some forms of bursting in Purkinje cells and layer 5 pyramidal cells. (Aa) Simultaneous recordings of somatic membrane potential (Middle) and dendritic Ca2+ fluorescence (Bottom) before (black) and after (red) dendrotomy. The stimulus was a 500-msec-long 7-nA current step applied at the soma (Top). The Purkinje cell in which these recordings were made is shown at right before dendrotomy. Red line, location of the Ca2+-imaging line scan; dashed white line, approximate site of dendrotomy. (Ab) Expanded views of the somatic membrane potential recorded in this cell, showing the first and last 50 msec of the response to the current step. Before dendrotomy, there was a rapidly inactivating burst of sodium APs at the beginning of the step, followed by slower rhythmic bursting during the latter part of the step (Left, arrow). After dendrotomy, the fast initial burst remained, but the late rhythmic bursting was abolished (Right). (Ac) Response of a different Purkinje cell to a 1-msec-long current step applied before (Left, 1.4-nA step) and after (Right, 0.5-nA step) dendrotomy. A second, attenuated sodium AP appears after dendrotomy (arrow). (Ba) A similar experiment was done on the layer 5 pyramidal cell (Right). The stimulus was a 100-Hz train of five 3-msec-long 2.2-nA current steps (Top). This stimulus elicited both a train of five APs (Middle) and, in control conditions, a Ca2+ transient (Bottom Left) recorded in the primary apical dendrite ≈90 μm from the soma (at red line in fluorescence image). After dendrotomy (at the dashed white line in the fluorescence image), the Ca2+ transient was abolished (Bottom Right). (Bb) Voltage response of this cell to a 450-pA current step applied at the soma. In control conditions (Left), the cell showed an initial burst of APs (arrow). After dendrotomy, bursting was abolished (Right). (Bc) Expanded view of the first AP in a train elicited in the same layer 5 cell before (black) and after (red) dendrotomy, showing the reduction in amplitude of the afterdepolarization (arrows).
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