BDNF in Synaptic Plasticity and Memory

Among members of the neurotrophin family, brainderived neurotrophic factor (BDNF) stands out for its ability to regulate synaptic plasticity and various cognitive functions of the brain. A Medline search with the terms ‘BDNF’ and ‘synaptic’ yields more than 700 research articles, mostly published in the last 7 years. Given that neurotrophins were initially defined as secretory factors that promote neuronal survival and differentiation during development, the role of BDNF in synaptic modulation was not recognized until late 1990s. A number of observations have aided in the realization that the primary function of BDNF is to regulate synaptic transmission and plasticity, rather than neuronal survival. One is that BDNF is widely distributed in many regions of the adult brain, with levels much higher than any other neurotrophins. The other is that the expression of BDNF can be rapidly enhanced by neuronal activity under conditions relevant to synaptic plasticity. Because neuronal activity is known to be crucial for synaptic plasticity, it was hypothesized that activity-dependent synaptic modulation is mediated by BDNF. Indeed, early studies demonstrated that BDNF mimics neuronal activity in altering the number and/or strength of synaptic connections. Subsequent studies revealed a much more complex and interesting picture. On the one hand, BDNF regulates various forms of synaptic plasticity, leading to changes in neuronal circuitry subserving complex behaviors. On the other hand, many aspects of BDNF cell biology, such as transcription and secretion, are tightly controlled by neuronal activity. Complex interactions between BDNF and neuronal activity may offer a plethora of means to control sophisticated cognitive functions of the mammalian brain.