Background
Changes in densities and in the morphology of dendritic spines in the hippocampus
are linked to hippocampal long-term potentiation (LTP), spatial learning, and depression.
Decreased brain-derived neurotrophic factor (BDNF) levels seem to contribute to depression.
Through its receptor trkB, BDNF is also involved in hippocampal LTP and hippocampus-dependent
learning. Conditionally gene-targeted mice in which the ablation of trkB is restricted
to the forebrain and occurs only during postnatal development display impaired learning
and LTP.
Methods
To examine whether there is a link among impaired hippocampal synaptic plasticity,
altered spines, and trkB receptors, we performed a quantitative analysis of spine
densities and spine length in the hippocampal area CA1 and the dentate gyrus in conditional
mutant mice (trkBlox/loxCaMKII-CRE mice). TrkB protein and mRNA levels were assayed using Western blot and
in situ hybridization analysis.
Results
Fifteen-week-old mutant mice exhibit specific reductions in spine densities and a
significant increase in spine length of apical and basal dendrites in area CA1. These
alterations correlate with a time- and region-specific reduction in full-length trkB
mRNA in the hippocampus.
Conclusions
TrkB functions in structural remodeling of hippocampal dendritic spines, which in
turn may affect synaptic transmission and plasticity.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons.Learn Mem. 2004; 11: 172-178
- Neurotrophins and depression.Trends Pharmacol Sci. 1999; 20: 59-61
- Synaptic integration in hippocampal CA1 pyramids.Prog Brain Res. 1990; 83: 215-222
- BDNF in schizophrenia, depression and corresponding animal models.Mol Psychiatry. 2005; 10: 345-352
- The Trk family of neurotrophin receptors.J Neurobiol. 1994; 25: 1386-1403
- Comparison of hippocampal dendritic spines in culture and in brain.J Neurosci. 1998; 18: 5294-5300
- Increased expression of brain-derived neurotrophic factor induces formation of basal dendrites and axonal branching in dentate granule cells in hippocampal explant cultures.J Neurosci. 2002; 22: 9754-9763
- Granule cell dendritic spine density in the rat hippocampus varies with spine shape and location.Neurosci Lett. 1985; 54: 219-224
- Ultrastructural localization of full-length trkB immunoreactivity in rat hippocampus suggests multiple roles in modulating activity-dependent synaptic plasticity.J Neurosci. 1999; 19: 8009-8026
- Dendritic spine changes associated with hippocampal long-term synaptic plasticity.Nature. 1999; 399: 66-70
- Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus.Nature. 1996; 381: 706-709
- Structural synaptic modifications associated with hippocampal LTP and behavioral learning.Cereb Cortex. 2000; 10: 952-962
- Short-term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus.Eur J Neurosci. 2005; 21: 1299-1303
- Cyclic AMP controls BDNF-induced TrkB phosphorylation and dendritic spine formation in mature hippocampal neurons.Nat Neurosci. 2005; 8: 164-172
- BDNF variation and mood disorders.Neuropsychopharmacology. 2005; 30: 1353-1361
- Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus.Science. 1995; 267: 1658-1662
- Systematic regulation of spine sizes and densities in pyramidal neurons.J Neurobiol. 2003; 56: 95-112
- Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor.Proc Natl Acad Sci U S A. 1995; 92: 8856-8860
- Reduced spinophilin but not microtubule-associated protein 2 expression in the hippocampal formation in schizophrenia and mood disorders.Am J Psychiatry. 2004; 161: 1848-1855
- Associative memory formation increases the observation of dendritic spines in the hippocampus.J Neurosci. 2003; 23: 659-665
- New spines, new memories.Mol Neurobiol. 2004; 29: 117-130
- Learning deficit in BDNF mutant mice.Eur J Neurosci. 1997; 9: 2581-2587
- Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions in the reelin haploinsufficient heterozygous reeler mouse.Proc Natl Acad Sci U S A. 2001; 98: 3477-3482
- TrkB has a cell-autonomous role in the establishment of hippocampal Schaffer collateral synapses.J Neurosci. 2005; 25: 3774-3786
- Brain-derived neurotrophic factor promotes the differentiation of various hippocampal nonpyramidal neurons, including Cajal-Retzius cells, in organotypic slice cultures.J Neurosci. 1996; 16: 675-687
- Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons.Nat Neurosci. 2001; 4: 1086-1092
- Total number and distribution of inhibitory and excitatory synapses on hippocampal CA1 pyramidal cells.Neuroscience. 2001; 102: 527-540
- Essential role for TrkB receptors in hippocampus-mediated learning.Neuron. 1999; 24: 401-414
- Essential role of brain-derived neurotrophic factor in adult hippocampal function.Proc Natl Acad Sci U S A. 2004; 101: 10827-10832
- Spine changes associated with long-term potentiation.Hippocampus. 2000; 10: 596-604
- Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons.Proc Natl Acad Sci U S A. 1998; 95: 11412-11417
- Structure and function of dendritic spines.Annu Rev Physiol. 2002; 64: 313-353
- Chronic fluoxetine administration to juvenile rats prevents age-associated dendritic spine proliferation in hippocampus.Brain Res. 2000; 883: 205-215
- Altered dendritic spine density in animal models of depression and in response to antidepressant treatment.Synapse. 2001; 42: 151-163
- Analysis of spine morphological plasticity in developing hippocampal pyramidal neurons.Hippocampus. 2000; 10: 561-568
- Optimization of Golgi methods for impregnation of brain tissue from humans and monkeys.J Neurosci Methods. 2003; 131: 1-7
- Inhibition of dendritic spine morphogenesis and synaptic transmission by activity-inducible protein Homer1a.J Neurosci. 2003; 23: 6327-6337
- NMDA receptor stimulation and brain-derived neurotrophic factor upregulate homer 1a mRNA via the mitogen-activated protein kinase cascade in cultured cerebellar granule cells.J Neurosci. 2001; 21: 3797-3805
- Association study of brain-derived neurotrophic factor in adults with a history of childhood onset mood disorder.Am J Med Genet B Neuropsychiatr Genet. 2004; 131: 16-19
- LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite.Nature. 1999; 402: 421-425
- Long-term potentiation is associated with new excitatory spine synapses on rat dentate granule cells.Learn Mem. 1996; 3: 218-228
- Functional neurogenesis in the adult hippocampus.Nature. 2002; 415: 1030-1034
- Dendritic spines elongate after stimulation of group 1 metabotropic glutamate receptors in cultured hippocampal neurons.Proc Natl Acad Sci U S A. 2002; 99: 1639-1644
- Spatial nitric oxide imaging using 1,2-diaminoanthraquinone to investigate the involvement of nitric oxide in long-term potentiation in rat brain slices.Neuroimage. 2002; 15: 633-639
- Amygdala-kindling induces alterations in neuronal densities and in densities of degenerated fibers.Hippocampus. 2004; 14: 311-318
- Molecular control of cortical dendrite development.Annu Rev Neurosci. 2002; (25127–49): 127-149
- Accelerated dendritic development of rat cortical pyramidal cells and interneurons after biolistic transfection with BDNF and NT4/5.Development. 2003; 130: 5827-5838
- Morphological changes in dendritic spines associated with long-term synaptic plasticity.Annu Rev Neurosci. 2001; 24: 1071-1089
Article info
Publication history
Published online: December 02, 2005
Accepted:
August 31,
2005
Received in revised form:
July 26,
2005
Received:
May 9,
2005
Identification
Copyright
© 2005 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.