BDNF and Activity-Dependent Synaptic Modulation: Figure 1.

Abstract

It is widely accepted that neuronal activity plays a pivotal role in synaptic plasticity. Neurotrophins have emerged recently as potent factors for synaptic modulation. The relationship between the activity and neurotrophic regulation of synapse development and plasticity, however, remains unclear. A prevailing hypothesis is that activity-dependent synaptic modulation is mediated by neurotrophins. An important but unresolved issue is how diffusible molecules such as neurotrophins achieve local and synapse-specific modulation. In this review, I discuss several potential mechanisms with which neuronal activity could control the synapse-specificity of neurotrophin regulation, with particular emphasis on BDNF. Data accumulated in recent years suggest that neuronal activity regulates the transcription of BDNF gene, the transport of BDNF mRNA and protein into dendrites, and the secretion of BDNF protein. There is also evidence for activity-dependent regulation of the trafficking of the BDNF receptor, TrkB, including its cell surface expression and ligand-induced endocytosis. Further study of these mechanisms will help us better understand how neurotrophins could mediate activity-dependent plasticity in a local and synapse-specific manner.Much of the brain's ability to adapt or modify itself in response to experience and environment lies in the plasticity of synaptic connections, both short-and long-terms. Substantial evidence indicates that the number and the strength of synapses can be changed by neuronal activity (Bliss and Collingridge 1993;Linden 1994;Malenka and Nicoll 1999;McEwen 1999). It is now widely accepted that activity-dependent modulation of synapses is critical for brain development as well as many cognitive functions in the adult. Molecular mechanisms that translate patterns of neuronal activity into specific changes in the structures and function of synapses, however, remain largely unknown. A hypothesis was put forward several years ago that neurotrophins may serve as molecular mediators for synaptic plasticity based on two observations: (1) The expression of neurotrophins is regulated by neuroelectric activity; and (2) neurotrophins could modulate the efficacy of synaptic transmission or the growth of dendrites and axons, the structural elements necessary for synaptogenesis

Interaction between BDNF and Serotonin: Role in Mood Disorders

“…Initially isolated as a secretory protein capable of promoting the survival of peripheral neurons, BDNF is now recognized as a plethoric factor able to regulate a wide repertoire of functions, including neuronal survival, migration, phenotypic differentiation, axonal and dendritic growth, and synapse formation (Huang and Reichardt, 2001;Lewin and Barde, 1996). In addition to its prominent role in neuronal survival and differentiation during development, BDNF has emerged as a key regulator of synaptic plasticity and behavior (McAllister et al, 1999;Poo, 2001;Lu, 2003). Recent evidence strongly implicates a role for BDNF in cognitive functions, notably in memory acquisition and consolidation.…”

“…BDNF has a complex genomic structure rendering it an ideal target for multiple and complex transcriptional regulation (West et al, 2001;Lu, 2003). Multiple upstream promoters, each individually regulated, drive a short 5 0 exon that is alternatively spliced onto a common 3 0 exon, which encodes the pre-proBDNF protein.…”

“…BDNF mRNA is translated in the ER into a precursor protein, which is folded in the trans-Golgi and then packaged into secretory vesicles (Lu, 2003). Upon correct folding, BDNF can be sorted into the constitutive (spontaneous release) or more frequently, into the regulatory (release in response to stimuli) secretory pathway.…”

The mood stabilizers lithium and valproate selectively activate the promoter IV of brain-derived neurotrophic factor in neurons

“…[1][2][3][4] BDNF is highly expressed in the cortex and hippocampus, 5 the brain areas thought to be critical for the control of mood, emotion and cognition. BDNF deficiency as well as other abnormalities have been linked to a variety of brain disorders including depression.…”

New hypothesis and treatment targets of depression: an integrated view of key findings

“…As an important NTF, BDNF mainly acts on neurons in the hippocampus, cerebral cortex, cerebellum, and basal forebrain, which are associated with higher functions such as learning and memory. BDNF also promotes neural proliferation and differentiation and has an anti-apoptotic function, as well as regulating synaptic morphology, information transmission and plasticity, thereby improving the symptoms of depression [23,24] . Interestingly, BDNF improves sleep architecture, especially slow-wave sleep, during antidepressant treatment, which refl ects enhanced synaptic plasticity and the synchronization of neuronal circuits [25] .…”