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Local structural balance and functional interaction of excitatory and inhibitory synapses in hippocampal dendrites

Nature Neuroscience volume 7, pages 373–379 (2004)Cite this article

Abstract

Theoretical and experimental studies on the computation of neural networks suggest that neural computation results from a dynamic interplay of excitatory and inhibitory (E/I) synaptic inputs. Precisely how E/I synapses are organized structurally and functionally to facilitate meaningful interaction remains elusive. Here we show that E/I synapses are regulated across dendritic trees to maintain a constant ratio of inputs in cultured rat hippocampal neurons. This structural arrangement is accompanied by an E/I functional balance maintained by a 'push-pull' feedback regulatory mechanism that is capable of adjusting E/I efficacies in a coordinated fashion. We also found that during activity, inhibitory synapses can determine the impact of adjacent excitatory synapses only if they are colocalized on the same dendritic branch and are activated simultaneously. These fundamental relationships among E/I synapses provide organizational principles relevant to deciphering the structural and functional basis for neural computation within dendritic branches.

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Figure 1: The structural balance of E/I synapses is maintained throughout hippocampal dendrites.
Figure 2: Functional balance of E/I synaptic inputs in a single neuron.
Figure 3: Activation of dendritic inhibitory synapses during bursts.
Figure 4: Spatial and temporal interactions between E/I inputs.
Figure 5: Feedback regulation of E/I synapses after perturbation of E/I balance.

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Acknowledgements

I thank E. Hueske and B. Li for participating in part of the experiments and contributing to Figure 1; M. Wilson, X.J. Wang, N. Wilson, S. Sadeghpour, B. Krupa and T. Emery for comments on the manuscript. This work was supported by grants from National Institutes of Health and the RIKEN–MIT Neuroscience Research Center.

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  1. Departments of Brain & Cognitive Sciences and Biology, Picower Centre for Learning and Memory, RIKEN–MIT Neuroscience Research Center, MIT, Cambridge, 02139, Massachusetts, USA

    Guosong Liu

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Correspondence to Guosong Liu.

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Supplementary information

Supplementary Fig. 1

Evaluation of the quality of space clamp in a cultured hippocampal neuron. a, Distribution of mEPSC rise time with a median value of 0.29 ms. The fast rise kinetics of mEPSCs suggest that active synapses are under reasonable degree of voltage clamp. b, Locations on the dendritic tree (S1, S2, S3) where glutamate receptors were activated by iontophrenic application of glutamate. Functional synapses are labeled by FM-dye labeling (red spots). S3 is approximately 130 μm away from the soma. c, Reversal potentials of synaptic currents in mV are S1 (0.6), S2 (3.5), and S3 (4.7). These results indicate that synapses whose locations are within 130 μm of the soma would receive an adequate steady-state level of voltage control. d, Comparison of time courses of glutamate evoked currents from various locations of dendritic tree. The shape of synaptic currents did not change significantly with increased distance between active synaptic sites and the site of somatic voltage clamp. This data suggests that most synapses receive a bandwidth of voltage clamp sufficient for recording changing time courses of synaptic conductance during synaptic transmission without introducing significant distortion. Therefore, the quality of the space clamp in this experimental condition is sufficient for detecting synaptic conductance originated from the active synapses at distant location of dendritic tree. (PDF 132 kb)

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Liu, G. Local structural balance and functional interaction of excitatory and inhibitory synapses in hippocampal dendrites. Nat Neurosci 7, 373–379 (2004). https://doi.org/10.1038/nn1206

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