The aim of this paper is to present an overview of three peptides that, by improving synaptic function, enhance learning and memory in laboratory rodents. We summarize their structure, their mechanisms of action, and their effects on synaptic and cognitive function. First we describe FGL, a peptide derived from the neural cell adhesion molecule which improves cognition by the activation of the PKC pathway that triggers an activity-dependent delivery of AMPA receptors to the synapses. Then we describe PTD4-PI3KAc peptide that by activating PI3K signaling pathway it promotes synapse and spine formation and enhances hippocampal dependent memory. Lastly, we describe a new peptide derived from the well-known tumor suppressor PTEN that prevents pathological interactions between PTEN and PDZ proteins at synapses during exposure to Amyloid beta. This action prevents memory deterioration in mouse model of Alzheimer’s disease. Together, this review indicates how learning and memory can be improved by manipulating synaptic function and number through pharmacological treatment with peptides, and it establishes synaptic function as a valid target for cognitive enhancement.
