<P> One reason for the popularity of the local protein synthesis hypothesis is that it provides a possible mechanism for the specificity associated with LTP . Specifically, if indeed local protein synthesis underlies L - LTP, only dendritic spines receiving LTP - inducing stimuli will undergo LTP; the potentiation will not be propagated to adjacent synapses . By contrast, global protein synthesis that occurs in the cell body requires that proteins be shipped out to every area of the cell, including synapses that have not received LTP - inducing stimuli . Whereas local protein synthesis provides a mechanism for specificity, global protein synthesis would seem to directly compromise it . However, as discussed later, the synaptic tagging hypothesis successfully reconciles global protein synthesis, synapse specificity, and associativity . </P> <P> Retrograde signaling is a hypothesis that attempts to explain that, while LTP is induced and expressed postsynaptically, some evidence suggests that it is expressed presynaptically as well . The hypothesis gets its name because normal synaptic transmission is directional and proceeds from the presynaptic to the postsynaptic cell . For induction to occur postsynaptically and be partially expressed presynaptically, a message must travel from the postsynaptic cell to the presynaptic cell in a retrograde (reverse) direction . Once there, the message presumably initiates a cascade of events that leads to a presynaptic component of expression, such as the increased probability of neurotransmitter vesicle release . </P> <P> Retrograde signaling is currently a contentious subject as some investigators do not believe the presynaptic cell contributes at all to the expression of LTP . Even among proponents of the hypothesis there is controversy over the identity of the messenger . Early thoughts focused on nitric oxide, while most recent evidence points to cell adhesion proteins . </P> <P> Before the local protein synthesis hypothesis gained significant support, there was general agreement that the protein synthesis underlying L - LTP occurred in the cell body . Further, there was thought that the products of this synthesis were shipped cell - wide in a nonspecific manner . It thus became necessary to explain how protein synthesis could occur in the cell body without compromising LTP's input specificity . The synaptic tagging hypothesis attempts to solve the cell's difficult problem of synthesizing proteins in the cell body but ensuring they only reach synapses that have received LTP - inducing stimuli . </P>

Who demonstrated that long term potentiation occurs as memory becomes established