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Background : The roles of neuromodulation in a neural network, such as in a cortical microcolumn, are still incompletely understood. Neuromodulation influences neural processing by presynaptic and postsynaptic regulation of synaptic efficacy. Neuromodulation also affects ion channels and intrinsic excitability. Methods : Synaptic efficacy modulation is an effective way to rapidly alter network density and topology. We alter network topology and density to measure the effect on spike synchronization. We also operate with differently parameterized neuron models which alter the neuron's intrinsic excitability, i.e., activation function. Results : We find that (a) fast synaptic efficacy modulation influences the amount of correlated spiking in a network. Also, (b) synchronization in a network influences the read-out of intrinsic properties. Highly synchronous input drives neurons, such that differences in intrinsic properties disappear, while asynchronous input lets intrinsic properties determine output behavior. Thus, altering network topology can alter the balance between intrinsically vs. synaptically driven network activity. Conclusion : We conclude that neuromodulation may allow a network to shift between a more synchronized transmission mode and a more asynchronous intrinsic read-out mode. This has significant implications for our understanding of the flexibility of cortical computations., Competing Interests: No competing interests were disclosed.

Background: The roles of neuromodulation in a neural network, such as in a cortical microcolumn, are still incompletely understood. Methods : (a) Neuromodulation influences neural processing by presynaptic and postsynaptic regulation of synaptic efficacy. Synaptic efficacy modulation can be an effective way to rapidly alter network density and topology. We show that altering network topology and density, will affect spike synchronization. Fast synaptic efficacy modulation may therefore influence the amount of correlated spiking in a network. (b) Neuromodulation also affects ion channel regulation for intrinsic excitability, which alters the neuron's activation function. Results : We show that synchronization in a network influences the read-out of these intrinsic properties. Highly synchronous input drives neurons, such that differences in intrinsic properties disappear, while asynchronous input lets intrinsic properties determine output behavior. Thus, altering network topology can alter the balance between intrinsically vs. synaptically driven network activity. Conclusion : We conclude that neuromodulation may allow a network to shift between a more synchronized transmission mode and a more asynchronous intrinsic read-out mode. This has significant implications for our understanding of the flexibility of cortical computations., Competing Interests: No competing interests were disclosed.

Membrane receptors for neuromodulators (NM) are highly regulated in their distribution and efficacy-a phenomenon which influences the individual cell's response to central signals of NM release. Even though NM receptor regulation is implicated in the pharmacological action of many drugs, and is also known to be influenced by various environmental factors, its functional consequences and modes of action are not well understood. In this paper we summarize relevant experimental evidence on NM receptor regulation (specifically dopamine D1 and D2 receptors) in order to explore its significance for neural and synaptic plasticity. We identify the relevant components of NM receptor regulation (receptor phosphorylation, receptor trafficking and sensitization of second-messenger pathways) gained from studies on cultured cells. Key principles in the regulation and control of short-term plasticity (sensitization) are identified, and a model is presented which employs direct and indirect feedback regulation of receptor efficacy. We also discuss long-term plasticity which involves shifts in receptor sensitivity and loss of responsivity to NM signals. Finally, we discuss the implications of NM receptor regulation for models of brain plasticity and memorization. We emphasize that a realistic model of brain plasticity will have to go beyond Hebbian models of long-term potentiation and depression. Plasticity in the distribution and efficacy of NM receptors may provide another important source of functional plasticity with implications for learning and memory.