cAMP binds to, and activates cAMP-dependent protein kinase A (PKA), which is located intracellularly in the neuron. The PKA consists of a holoenzyme - it is a compound which becomes active due to the combination of an enzyme with a coenzyme. The PKA enzyme also contains two catalytic PKS-Cα subunits, and a regulator PKA-R subunit dimer. The PKA holoenzyme is inactive under normal conditions, however, when cAMP molecules that are produced earlier in the signal transduction mechanism combine with the enzyme, PKA undergoes a conformational change. This activates it, giving it the ability to catalyse substrate phosphorylation. CREB (cAMP response element binding protein) belongs to a family of transcription factors and is positioned in the nucleus of the neuron. When the PKA is activated, it phosphorylates the CREB protein (adds a high energy phosphate group) and activates it. The CREB protein binds to cAMP response elements CRE, and can either increase or decrease the transcription of certain genes. The cAMP/PKA/CREB signalling pathway described above is crucial in memory formation and pain modulation. It is also significant in the induction and maintenance of long-term potentiation, which is a phenomenon that underlies synaptic plasticity - the ability of synapses to strengthen or weaken over time.