pubmed.ncbi.nlm.nih.gov

Neuron network activity scales exponentially with synapse density - PubMed

  • ️Wed Jun 01 0140

Neuron network activity scales exponentially with synapse density

G J Brewer et al. J Neural Eng. 2009 Feb.

Abstract

Neuronal network output in the cortex as a function of synapse density during development has not been explicitly determined. Synaptic scaling in cortical brain networks seems to alter excitatory and inhibitory synaptic inputs to produce a representative rate of synaptic output. Here, we cultured rat hippocampal neurons over a three-week period to correlate synapse density with the increase in spontaneous spiking activity. We followed the network development as synapse formation and spike rate in two serum-free media optimized for either (a) neuron survival (Neurobasal/B27) or (b) spike rate (NbActiv4). We found that while synaptophysin synapse density increased linearly with development, spike rates increased exponentially in developing neuronal networks. Synaptic receptor components NR1, GluR1 and GABA-A also increase linearly but with more excitatory receptors than inhibitory. These results suggest that the brain's information processing capability gains more from increasing connectivity of the processing units than increasing processing units, much as Internet information flow increases much faster than the linear number of nodes and connections.

PubMed Disclaimer

Figures

Figure 1
Figure 1

Development of spontaneous action potentials in hippocampal cultures with NbActiv4 or Neurobasal/B27 media. Spontaneous activity over 0.03 Hz of neurons cultured in Neurobasal/B27 (open bars, n = 3 electrode arrays) or NbActiv4 (closed bars, n = 3) on multi-electrode arrays. Day 21 data are from an n of 5 electrode arrays each.

Figure 2
Figure 2

Synaptic development of hippocampal neurons in NbActiv4 increases synaptophysin and GluR1 synaptic puncta earlier than in Neurobasal/B27. Green immunoreactive synaptophysin and red GluR1 puncta for neurons in Neurobasal/B27 ((A), (C) and (E)) or NbActiv4 ((B), (D) and (F)) cultured for 7 days ((A) and (B)), 14 days ((C) and (D)) or 21 days ((E) and (F)). Scale bars equal 20 μm. (G) Analysis of synaptophysin puncta by density separation into three classes from entire image in (F) (red—brightest, green, yellow—dimmest). (H) Similar analysis of GluR1 puncta by density separation into four classes (red—brightest, green, yellow, blue—dimmest). (I) Synaptophysin puncta densities for neurons increase linearly with development in Neurobasal/B27 (black open symbols, n = 16) or NbActiv4 (red closed symbols, n = 16). (J) Similar linear increases for GluR1 puncta with time in culture.

Figure 3
Figure 3

Neurons in NbActiv4 increase development of NR1 and GABAA synaptic puncta faster than in Neurobasal/B27. Immunoreactive green NR1 and red GABA puncta in Neurobasal/B27 ((A), (C) and (E)) or NbActiv4 ((B), (D) and (F)) at day 7 ((A) and (B)), day 14 ((C) and (D)) or day 21 ((E) and (F)). Scale bars are 20 μm. Analysis of NR1 puncta (G) and GABA puncta (H) by density separation into four classes from region outlined in (F) (red—brightest, green, yellow, then blue—dimmest). (I) NR1 puncta densities increase linearly with development in Neurobasal/B27 (black open symbols, n = 16) or NbActiv4 (red closed symbols, n = 16). (J) Similar linear increases for GABA puncta with time in culture.

Figure 4
Figure 4

Action potential frequency per synaptophysin density increases at an exponential rate. Spike frequency for neurons cultured in NbActiv4 (closed red symbols, R2 = 0.92, n = 3) increases exponentially as a function of synapses 1.97 times that in Neurobasal/B27 (open black symbols, R2 = 0.88, n = 3). The data are from figures 1 and 2 at developmental day 7 (circles), 14 (squares) and 21 (triangles).

Similar articles

Cited by

References

    1. Barbin G, Pollard H, Gaiarsa JL, Ben Ari Y. Involvement of GABAA receptors in the outgrowth of cultured hippocampal neurons. Neurosci Lett. 1993;152:150–4. - PubMed
    1. Boehler MD, Wheeler BC, Brewer GJ. Added astroglia promote greater synapse density and higher activity in neuronal network. Neuron Glia Biol. 2007;3:127–40. - PMC - PubMed
    1. Braitenberg V, Schuz A. Cortex: Statistics and Geometry of Neuronal Connectivity. 2. Berlin: Springer; 2004. pp. 19–35.
    1. Brewer GJ, Boehler MD, Jones TT, Wheeler BC. NbActiv4 medium improvement to Neurobasal/B27 increases neuron synapse densities and network spike rates on multielectrode arrays. J Neurosci Methods. 2008;170:181–7. - PMC - PubMed
    1. Brewer GJ, Reichensperger JD, Brinton RD. Prevention of age-related dysregulation of calcium dynamics by estrogen in neurons. Neurobiol Aging. 2006;27:306–17. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources