Synaptic Innervation Density Is Regulated by Neuron-Derived BDNF

Causing, Carrie G.; Gloster, Andrew T.; Aloyz, Raquel; Bamji, Shernaz X.; Chang, Eddie L.; Fawcett, James P.; Kuchel, George A.; Miller, Freda D.

doi:10.1016/s0896-6273(00)80266-4

Cited by 263 publications

(189 citation statements)

References 41 publications

Supporting

Mentioning

173

Contrasting

Unclassified

Order By: Relevance

“…Local protein synthesis triggered by BDNF may stabilize efficacy changes by stimulating more activity-dependent phosphorylation of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and assisting in remodeling of the postsynaptic element into a more efficacious configuration. In accord with the latter idea, stabilization of LTP requires expression of Arc during a period (27) when the structural modifications associated with LTP are beginning to emerge (47), and BDNF signaling has been shown to have profound effects on synaptic density (48,49), the thickness of the postsynaptic density (50), and the length of the active zone at asymmetric synapses (38).…”

Section: Discussionmentioning

confidence: 88%

The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes

Yin

Edelman²,

Vanderklish³

2002

Proc. Natl. Acad. Sci. U.S.A.

248

189

View full text Add to dashboard Cite

Protein synthesis in neurons is essential for the consolidation of memory and for the stabilization of activity-dependent forms of synaptic plasticity such as long-term potentiation (LTP). Activitydependent translation of dendritically localized mRNAs has been proposed to be a critical source of new proteins necessary for synaptic change. mRNA for the activity-regulated cytoskeletal protein, Arc, is transcribed during LTP and learning, and disruption of its translation gives rise to deficits in both. We have found that selective translation of Arc in a synaptoneurosomal preparation is induced by the brain-derived neurotrophic factor, a neurotrophin that is released during high-frequency stimulation patterns used to elicit LTP. This effect involves signaling through the TrkB receptor and is blocked by the N-methyl-D-aspartate-type glutamate receptor antagonist, MK801. The results suggest there is a synergy between neurotrophic and ionotropic mechanisms that may influence the specificity and duration of changes in synaptic efficacy at glutamatergic synapses.T he brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor (NGF) superfamily of neurotrophins (1, 2), influences the differentiation and survival of neurons and the maintenance of their arborizations (3-6). Other data suggest that BDNF is also involved in both short-and long-term plasticity of glutamatergic synapses (7,8). BDNF signaling enhances synaptic maturation and increases synaptic density in the hippocampus (9), and in the adult the synthesis and secretion of BDNF continue to be regulated by activity (10-12). Exogenous application of BDNF induces a rapid and persistent enhancement of synaptic transmission in hippocampal and cortical preparations (13,14) and facilitates the induction of long-term potentiation (LTP) in slices from young animals (15). Stimulation patterns used to elicit LTP also result in release of the BDNF protein from presynaptic terminals (16,17).Local protein synthesis may influence changes in synaptic efficacy induced by BDNF. Early and reversible effects of BDNF involve pre-and postsynaptic changes that do not require protein synthesis. For example, application of BDNF enhances evoked glutamate release (18) and increases the probability that the N-methyl-D-aspartate (NMDA) receptor channel will be open (19). Longer-term influences on synaptic efficacy, however, may require BDNF-induced local protein synthesis. BDNF-induced synaptic potentiation in hippocampal slices is blocked by inhibitors of protein synthesis (20). Potentiation induced by BDNF can be obtained in slices in which synapses have been severed from cell bodies, suggesting that synthesis of the required protein(s) is dendritically localized (20). In accord with this possibility, it has been shown that BDNF specifically induces the expression of transfected c-myc in dissected dendrites (21), and the dendritic synthesis of a reporter protein construct flanked by the 5Ј and 3Ј untranslated regions of ␣-calmodulin-dependent protein kinase II ]. These ...

show abstract

Section: Discussionmentioning

confidence: 88%

The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes

Yin

Edelman²,

Vanderklish³

2002

Proc. Natl. Acad. Sci. U.S.A.

248

189

View full text Add to dashboard Cite

show abstract

“…41 Upregulation of BDNF increases neuronal cell size and synaptic density, 42 two parameters that are putatively reduced in the brain of patients with schizophrenia, as evidenced above. BDNF is synthesized by neurons in the frontal cortex of rodents 14,[43][44][45][46] and pyramidal neurons in the dorsolateral prefrontal cortex of Rhesus monkeys.…”

mentioning

confidence: 81%

Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia

et al. 2003

View full text Add to dashboard Cite

Anatomical and molecular abnormalities of excitatory neurons in the dorsolateral prefrontal cortex (DLPFC) are found in schizophrenia. We hypothesized that brain-derived neurotrophic factor (BDNF), a protein capable of increasing pyramidal neuron spine density and augmenting synaptic efficacy of glutamate, may be abnormally expressed in the DLPFC of patients with schizophrenia. Using an RNase protection assay and Western blotting, we detected a significant reduction in BDNF mRNA (mean = 23%) and protein (mean = 40%) in the DLPFC of patients with schizophrenia compared to normal individuals. At the cellular level, BDNF mRNA was expressed at varying intensities in pyramidal neurons throughout layers II, III, V, and VI of DLPFC. In patients with schizophrenia; neuronal BDNF expression was decreased in layers III, V and VI. Our study demonstrates a reduction in BDNF production and availability in the DLPFC of schizophrenics, and suggests that intrinsic cortical neurons, afferent neurons, and target neurons may receive less trophic support in this disorder.

show abstract

“…Manipulations of NGF levels were shown early on to regulate both the strength and the number of presynaptic inputs (Nja and Purves 1978). In mice overexpressing BDNF in sympathetic neurons, increased numbers of synapses were observed, whereas decreases were seen in bdnf−/− animals (Causing et al 1997). In the hippocampus of mice carrying mutations in trkB, trkC, or in both genes, lower densities of synaptic contact were recorded in the hippocampus.…”

Section: Neurotrophins and Synaptic Transmissionmentioning

confidence: 99%

Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system

Bibel

Barde²

2000

Genes Dev.

967

702

View full text Add to dashboard Cite

Synaptic Innervation Density Is Regulated by Neuron-Derived BDNF

Cited by 263 publications

References 41 publications

The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes

The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes

Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia

Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system

Contact Info

Product

Resources

About