Change in the efficacy or connections of the junctions (synapses) between neurons in the nervous system. It is a crucial process that underlies modification of an animal’s behaviour during development and in response to previous activity or experience, including learning and memory. Various mechanisms produce changes in the efficacy of synapses, which can range in duration from fractions of a second to days or weeks. For example, the arrival of impulses in rapid succession at a motor end plate causes an augmented postsynaptic potential lasting perhaps 100–200 ms (see facilitation). If a motor neuron is stimulated at high frequency for a long period (i.e. tetanic stimulation), it is followed by a period of reduced synaptic efficacy (synaptic depression), due to depletion of synaptic vesicles in the presynaptic nerve endings. Following recovery from synaptic depression, a synapse often displays post-tetanic potentiation, in which the amplitude of the response is increased relative to that obtained by a comparable stimulus before tetanic stimulation. The activity of synapses is also modulated by various agents, including neurotransmitters, released into the vicinity by other nerve endings or present in the bloodstream. For example in the sluglike gastropod mollusc Aplysia, enhanced sensitivity to a stimulus (behavioural sensitization) is triggered by the release of serotonin. This facilitates the release of neurotransmitter at certain synapses, thereby increasing the amplitude and duration of the postsynaptic potentials for several minutes. In such processes as learning and memory it is thought that long-term potentiation (LTP) and long-term depression (LTD) play important roles in strengthening or inhibiting existing neural circuits of the brain, with effects lasting for hours, days, or longer. Studies on mammalian brains have revealed that two types of glutamate receptors, the AMPA and NMDA receptors, play crucial roles in both LTP and LTD. For example, the long-lasting increase in the response of a postsynaptic cell that typifies LTP involves a series of action potentials arriving simultaneously at both the presynaptic cell and at other synapses nearby. This activates NMDA receptors in the postsynaptic membrane and triggers the recruitment of AMPA receptors, thereby stably increasing the size of the excitatory postsynaptic potential.