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. 2003 Dec 1;553(Pt 2):497-509.
doi: 10.1113/jphysiol.2003.052639. Epub 2003 Sep 18.

Miniature synaptic transmission and BDNF modulate dendritic spine growth and form in rat CA1 neurones

William J Tyler  1 , Lucas Pozzo-Miller
Affiliations

Miniature synaptic transmission and BDNF modulate dendritic spine growth and form in rat CA1 neurones

William J Tyler et al. J Physiol. .

Abstract

The refinement and plasticity of neuronal connections require synaptic activity and neurotrophin signalling; their specific contributions and interplay are, however, poorly understood. We show here that brain-derived neurotrophic factor (BDNF) increased spine density in apical dendrites of CA1 pyramidal neurones in organotypic slice cultures prepared from postnatal rat hippocampal slices. This effect was observed also in the absence of action potentials, and even when miniature synaptic transmission was inhibited with botulinum neurotoxin C (BoNT/C). There were, however, marked differences in the morphology of individual spines induced by BDNF across these different levels of spontaneous ongoing synaptic activity. During both normal synaptic transmission, and when action potentials were blocked with TTX, BDNF increased the proportion of stubby, type-I spines. However, when SNARE-dependent vesicular release was inhibited with BoNT/C, BDNF increased the proportion of thin, type-III spines. Our results indicate that BDNF increases spine density irrespective of the levels of synaptic transmission. In addition, miniature synaptic transmission provides sufficient activity for the functional translation of BDNF-triggered spinogenesis into clearly defined morphological spine types, favouring those spines potentially responsible for coordinated Ca2+ transients thought to mediate synaptic plasticity. We propose that BDNF/TrkB signalling represents a mechanism of expression of both morphological and physiological homeostatic plasticity in the hippocampus, leading to a more efficient synaptic information transfer across widespread levels of synaptic activity.

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Figures

Figure 1
Figure 1. Classification of spine types
The classification is based on the spine length, the diameter of the head and the diameter of the neck (based on Harris et al. 1992).
Figure 2
Figure 2. Under conditions of normal neuronal activity, BDNF increases the frequency of AMPA-mEPSCs and dendritic spine density while promoting the formation of stubby spines (type-I)
A, probability distributions of the mean amplitudes of AMPA-mediated mEPSCs recorded from CA1 pyramidal neurones in serum-free control (left) and brain-derived neurotrophic factor (BDNF)-treated (right) hippocampal slice cultures. Mean frequency, amplitude and representative continuous records of spontaneous mEPSCs are also shown for each group (inset). B, maximum-intensity z-projection confocal images of representative apical dendritic segments of CA1 pyramidal neurones filled with Alexa-594 in serum-free control (left), BDNF (centre) and 20 % horse serum (HSM) (right) slice cultures. C, histogram plots of the proportion of each morphologically distinct spine type (I, II and III) in control, BDNF and 20 % HSM-treated slice cultures. In this and all remaining figures, asterisks indicate statistically significant differences (P < 0.05).
Figure 5
Figure 5. BDNF induces dendritic spine formation, and selectively affects the morphological maturation of spines across several distinct levels of synaptic transmission
A, cumulative probability distributions of AMPA-mEPSC amplitudes (left) and frequencies (right) for all recordings obtained from CA1 pyramidal neurones in serum-free control (^), BDNF (•), TTX (▵), TTX-BDNF (▾), BoNT/C (□) and BoNT/C-BDNF-treated (▪) hippocampal slice cultures. B, scatter plot illustrating the mean number of type-I (▪, solid line), type-II (•, dashed line) and type-III (▾, dotted line) dendritic spines per 10 µm of apical dendrite in each treatment group, and presented as control vs. BDNF, TTX vs. TTX-BDNF and BoNT/C vs. BoNT/C-BDNF comparisons. Summation of the densities for each spine type yields overall spine density (T), expressed in mean number of spines per 10 µm of secondary and tertiary apical dendrites.
Figure 3
Figure 3. Action potential-independent neurotransmitter release (minis) provides sufficient activity for BDNF to induce spine formation, and preferentially increase the proportion of stubby spines (type-I)
A, probability distributions of the mean amplitudes of AMPA-mediated mEPSCs in slice cultures treated with TTX (left) and TTX-BDNF (right) slice cultures. B, representative dendritic segments of CA1 pyramidal neurones in slice cultures treated with TTX (top) and TTX-BDNF (bottom). C, histogram plots of the proportion of each morphologically distinct spine type in slice cultures treated with TTX and TTX-BDNF. Data from serum-free controls (from Fig. 2) are presented here to facilitate visual comparisons.
Figure 4
Figure 4. In the near absence of SNARE-dependent neurotransmitter release, BDNF induces spine formation, while increasing the proportion of thin spines (type-III)
A, probability distributions of the mean amplitudes of AMPA-mediated mEPSCs in slice cultures treated with botulinum neurotoxin C (BoNT/C) (left) and BoNT/C-BDNF (right). B, representative dendritic segments of CA1 pyramidal neurones in BoNT/C (top) and BoNT/C-BDNF (bottom) slice cultures. C, histogram plots of the proportion of each morphologically distinct spine type in slice cultures treated with BoNT/C and BoNT/C-BDNF. Data from serum-free controls (from Fig. 2) are presented here to facilitate visual comparisons.
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References

    1. Bi G, Poo M. Synaptic modification by correlated activity: Hebb's postulate revisited. Annu Rev Neurosci. 2001;24:139–166. - PubMed
    1. Blasi J, Chapman ER, Yamasaki S, Binz T, Niemann H, Jahn R. Botulinum neurotoxin C1 blocks neurotransmitter release by means of cleaving HPC-1/syntaxin. EMBO J. 1993;12:4821–4828. - PMC - PubMed
    1. Burrone J, O'Byrne M, Murthy VN. Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons. Nature. 2002;420:414–418. - PubMed
    1. Cabelli RJ, Shelton DL, Segal RA, Shatz CJ. Blockade of endogenous ligands of trkB inhibits formation of ocular dominance columns. Neuron. 1997;19:63–76. - PubMed
    1. Cajal SR. Histologie du Systeme Nerveux de l'Homme et des Vertebres. Vol. 1. Paris: 1909.

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