This study investigates the differential signaling via the same axon of neocortical pyramidal neurons. It reveals that each synaptic connection established by these neurons is potentially unique, with differences in the number and dendritic locations of synaptic contacts, synaptic strength, and rates of depression and recovery. The same axon can mediate frequency-dependent depression and facilitation depending on the target neuron, suggesting that the nature of the target neurons influences synaptic properties. Facilitating-type synapses from three pyramidal neurons onto a single interneuron are qualitatively similar but differ in the time courses of facilitation and depression, indicating different pre-postsynaptic interactions. Mathematical analysis of synaptic transfer functions shows that presynaptic rates, integrals of rates, and derivatives of rates are transferred to targets based on synaptic parameters and presynaptic activity history. This heterogeneity allows multiple synaptic representations of the same presynaptic action potential train, suggesting complex regulation. The study proposes that differential signaling is a key mechanism in neocortical information processing, regulated by synaptic modifications. Neuronal signaling in the neocortex has been debated, with focus on how frequency-dependent changes in synaptic transmission affect action potential (AP) train features. Dual recordings in the neocortex show that synaptic connections from pyramidal neurons onto interneurons can display frequency-dependent facilitation, while onto pyramidal neurons typically display depression, suggesting differential transmission in the mammalian neocortex. Differential transmission to thousands of target neurons could mean different features of the same AP train are transmitted to each target, indicating computational complexity. The study aims to establish synaptic property heterogeneity, a general approach to synaptic property mosaics, and assess transfer functions of different synapses. Triple and quadruple neuron recordings in rat neocortex were used to compare responses in different target neurons and synapses from the same morphological class. Synaptic properties were analyzed with a phenomenological model, leading to mathematical descriptions of AP train features transmitted by these synapses. The study found that synaptic connections onto the same class of pyramidal neuron differ in numbers and dendritic locations of contacts, synaptic efficacy, and recovery times. Synaptic connections onto pyramidal neurons and interneurons displayed depression and facilitation, respectively. Convergent connections from the same class of neuron onto a single interneuron showed different facilitation and depression time courses, indicating different pre-postsynaptic interactions. Quantitative analysis of synaptic parameters showed heterogeneity in absolute synaptic efficacy, utilization of synaptic efficacy, and recovery times. The study also found that facilitating synapses have higher peak frequencies and limiting frequencies compared to depressing synapses. Heterogeneity in synaptic transfer functions indicates that each synaptic connection can transmit different features of presynaptic AP activity, leading to differential signaling. The study concludes that differential signaling is a key mechanism in neocortical information processing, regulated by synaptic modifications.This study investigates the differential signaling via the same axon of neocortical pyramidal neurons. It reveals that each synaptic connection established by these neurons is potentially unique, with differences in the number and dendritic locations of synaptic contacts, synaptic strength, and rates of depression and recovery. The same axon can mediate frequency-dependent depression and facilitation depending on the target neuron, suggesting that the nature of the target neurons influences synaptic properties. Facilitating-type synapses from three pyramidal neurons onto a single interneuron are qualitatively similar but differ in the time courses of facilitation and depression, indicating different pre-postsynaptic interactions. Mathematical analysis of synaptic transfer functions shows that presynaptic rates, integrals of rates, and derivatives of rates are transferred to targets based on synaptic parameters and presynaptic activity history. This heterogeneity allows multiple synaptic representations of the same presynaptic action potential train, suggesting complex regulation. The study proposes that differential signaling is a key mechanism in neocortical information processing, regulated by synaptic modifications. Neuronal signaling in the neocortex has been debated, with focus on how frequency-dependent changes in synaptic transmission affect action potential (AP) train features. Dual recordings in the neocortex show that synaptic connections from pyramidal neurons onto interneurons can display frequency-dependent facilitation, while onto pyramidal neurons typically display depression, suggesting differential transmission in the mammalian neocortex. Differential transmission to thousands of target neurons could mean different features of the same AP train are transmitted to each target, indicating computational complexity. The study aims to establish synaptic property heterogeneity, a general approach to synaptic property mosaics, and assess transfer functions of different synapses. Triple and quadruple neuron recordings in rat neocortex were used to compare responses in different target neurons and synapses from the same morphological class. Synaptic properties were analyzed with a phenomenological model, leading to mathematical descriptions of AP train features transmitted by these synapses. The study found that synaptic connections onto the same class of pyramidal neuron differ in numbers and dendritic locations of contacts, synaptic efficacy, and recovery times. Synaptic connections onto pyramidal neurons and interneurons displayed depression and facilitation, respectively. Convergent connections from the same class of neuron onto a single interneuron showed different facilitation and depression time courses, indicating different pre-postsynaptic interactions. Quantitative analysis of synaptic parameters showed heterogeneity in absolute synaptic efficacy, utilization of synaptic efficacy, and recovery times. The study also found that facilitating synapses have higher peak frequencies and limiting frequencies compared to depressing synapses. Heterogeneity in synaptic transfer functions indicates that each synaptic connection can transmit different features of presynaptic AP activity, leading to differential signaling. The study concludes that differential signaling is a key mechanism in neocortical information processing, regulated by synaptic modifications.