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This manuscript reviews the function and fundamental characteristics of the neurotrophins and their receptors to introduce the reader to the differential effects exhibited by the neurotrophins; brain-derived neurotrophic factor and neurotrophin 4/5 when acted together after sequential presentation. The neuro-trophin 4/5 exhibits an inhibitory action on the modulatory effect of brain-derived neurotrophic factor in corticostriatal synapses when they are administered sequentially (brain-derived neurotrophic factor to neurotrophin 4/5). This inhibitory effect has not been previously documented and is relevant for these neu-rotrophins as both of them stimulate the TrkB receptor. The additive effect of these neurotrophins is also discussed and occurs when neurotrophin 4/5 exposure is followed by brain-derived neurotrophic factor in a mouse model of striatal degeneration. Occlusive and additive effects of both neurotrophins are accompa-nied by changes in the expression of the TrkB receptor isoforms,specifically TrkB-T1 and TrkB-FL,as well as differences in phosphorylation levels of the TrkB receptor. The results of the experiments described raise several questions to inquire about the role that TrkB-T1 receptor plays in striatal physiology,as well as the functional relevance of the interaction of brain-derived neurotrophic factor and neurotrophin 4/5 in the brain and more specifically at the striatal circuits in normal as well as pathological conditions.