Elsevier

Neuroscience

Volume 102, Issue 3, 5 February 2001, Pages 527-540
Neuroscience

Total number and distribution of inhibitory and excitatory synapses on hippocampal CA1 pyramidal cells

https://doi.org/10.1016/S0306-4522(00)00496-6Get rights and content

Abstract

The integrative properties of neurons depend strongly on the number, proportions and distribution of excitatory and inhibitory synaptic inputs they receive. In this study the three-dimensional geometry of dendritic trees and the density of symmetrical and asymmetrical synapses on different cellular compartments of rat hippocampal CA1 area pyramidal cells was measured to calculate the total number and distribution of excitatory and inhibitory inputs on a single cell.

A single pyramidal cell has ∼12,000 μm dendrites and receives around 30,000 excitatory and 1700 inhibitory inputs, of which 40% are concentrated in the perisomatic region and 20% on dendrites in the stratum lacunosum-moleculare. The pre- and post-synaptic features suggest that CA1 pyramidal cell dendrites are heterogeneous. Strata radiatum and oriens dendrites are similar and differ from stratum lacunosum-moleculare dendrites. Proximal apical and basal strata radiatum and oriens dendrites are spine-free or sparsely spiny. Distal strata radiatum and oriens dendrites (forming 68.5% of the pyramidal cells’ dendritic tree) are densely spiny; their excitatory inputs terminate exclusively on dendritic spines, while inhibitory inputs target only dendritic shafts. The proportion of inhibitory inputs on distal spiny strata radiatum and oriens dendrites is low (∼3%). In contrast, proximal dendritic segments receive mostly (70–100%) inhibitory inputs. Only inhibitory inputs innervate the somata (77–103 per cell) and axon initial segments. Dendrites in the stratum lacunosum-moleculare possess moderate to small amounts of spines. Excitatory synapses on stratum lacunosum-moleculare dendrites are larger than the synapses in other layers, are frequently perforated (∼40%) and can be located on dendritic shafts. Inhibitory inputs, whose percentage is relatively high (∼14–17%), also terminate on dendritic spines.

Our results indicate that: (i) the highly convergent excitation arriving onto the distal dendrites of pyramidal cells is primarily controlled by proximally located inhibition; (ii) the organization of excitatory and inhibitory inputs in layers receiving Schaffer collateral input (radiatum/oriens) versus perforant path input (lacunosum-moleculare) is significantly different.

Section snippets

Experimental procedures

Seven adult (300 g) male Wistar rats (Charles River, Budapest) were used in these experiments. The animals were anesthetized with Equithesin (chlornembutal, 0.3 ml per 100 g of body weight). Biotinylated dextran amine (BDA, Molecular Probes; 10% in phosphate buffer, PB) was injected into the CA1 region at the following coordinates: Bregma: −3.2 mm; lateral: 2 mm (left and right); −2.4 mm from pia mater; and Bregma: −4.3 mm; lateral: 3 mm (left and right); −2.4 from pia mater. The BDA was

Light microscopy

Biotinylated dextran amine (BDA) injected into the CA1 area labeled a dense group of cells in the center of the injection site, as well as cells several hundred micrometers away from the injection site, probably by retrograde transport. These solitary cells (Fig. 1D) showed very dense precipitation of DAB so that dendrites could be followed and morphological features described in detail (Fig. 1C). The labeling visualized the fine dendritic spines and the dendrites could be followed until their

Discussion

The main findings of the present study are: (1) Pyramidal cell dendrites are heterogeneous in diameter, spine density and in the number of asymmetrical and symmetrical synaptic inputs. Strata radiatum and oriens dendrites (SRO) are similar to each other both at the light and electron microscopic levels and are different from stratum lacunosum-moleculare dendrites (SLM) with respect to dendritic shaft diameter, branching pattern and spine density. (2) The ratio of symmetrical versus asymmetrical

Acknowledgements

We are grateful to Drs L. Acsády, K. Kaila and R. Miles for helpful discussions and comments on the manuscript, and to Mrs E. Borók, Mr G. Goda and Mrs E. Oswald for excellent technical assistance. This work was supported by the Howard Hughes Medical Institute; the McDonnell Foundation; NIH (MH 54671); FPI grants, Ministerio de Edución y Ciencia, Spain; and OTKA (Hungarian Scientific Research Found, T23261), Hungary.

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