It is well known that central synapses are highly plastic, and long-term changes in synaptic transmission contribute to different functions of the brain throughout the lifespan. Two major forms of synaptic plasticity have been widely investigated: long-term potentiation (or called LTP) and long-term depression (or called LTD). While LTP can enhance synaptic functions in certain regions of the brain, LTD attenuates or reduces the efficacy of synaptic transmission. Such biphasic synaptic plasticity is not limited at excitatory, glutamatergic synapses. Both LTP and LTD have been also reported in inhibitory synapses, and underlying cellular and molecular mechanisms are different. Recent studies using different induction protocols reveal that the mechanisms for central LTP are likely to be different, depending the induction protocols, regions of the CNS, input fibers and postsynaptic neurons recorded [1
]. There is no doubt that many different molecular targets will be continuously revealed in future, one urgent task is to verify the physiological or pathological relevant of synaptic LTP/LTD induced by experimental induction protocols. Furthermore, new forms of LTP and LTD remain to be discovered to mimic physiological and/or pathological changes under in vivo
conditions (e.g., presynaptic enhancement of neurotransmitter release after tissue injury in the anterior cingulate cortex (ACC) (see [6
What has been recognized about the potential functions of LTP is its contribution to many key brains functions in addition to learning and memory [7
]. At the spinal cord dorsal horn where the first sensory synapses are located, LTP of sensory synaptic transmission can be induced by different experimental protocols [12
] or peripheral injury [14
]. Potentiated excitatory synaptic transmission is believed to contribute to spinal sensitization that at least in part attributes to behavioral hyperalgesia and allodynia during chronic pain. In the basolateral amygdala, LTP can be induced between thalamic/cortical inputs and postsynaptic principle neurons [15
] or fear conditions [11
], such enhanced responses are important for encoding fearful information. In the hippocampal CA1 region where most of LTP studies have been reported, LTP can be induced and reliable detected, even with field recording electrodes [7
]. However, despite a huge amount of literature on hippocampal LTP, it remains to be demonstrated that if a simple spatial training trial may induce LTP in certain population of CA1 neurons.
Finally, in the prefrontal cortical (PFC) neurons including the ACC, LTP is induced by the pairing, spike-timing and theta burst protocols [16
] as well as peripheral injury [17
]. It has been proposed that the injury caused synaptic potentiation contribute to chronic pain and pain-related high brain functions including fear and emotion [18
]. Therefore, it is clear that studying central LTP provides fundamental mechanisms for brain functions – from pain transmission to fear and chronic pain.