The significance of action potential bursting in the brain reward circuit.

The brain reward circuit consists of specialized cortical and subcortical structural components that code for various cognitive aspects of goal-directed behavior. These components include the prefrontal cortex (PFC), amygdala (AMY), nucleus accumbens (Nac), subiculum (SUB) of the hippocampal formation, and the dopamine (DA) neurons in the ventral tegmental area (VTA). Both serial and parallel processing in the different components of the circuit code the various aspects of reward-related behavior. Individual neurons within each component have developed specialized intrinsic membrane properties that have led them to be typically defined as either single spiking or high frequency burst-firing neurons. However, a strict definition based on the output mode may not be appropriate. Under the right conditions, neurons can switch between bursting and single-spiking modes, therefore providing a conditional output state. The preferred mode of each individual neuron depends on a combination of different plastic neuronal properties such as, dendritic architecture, neuromodulation, intracellular calcium (Ca(++)) buffering, excitatory and inhibitory synaptic strength, and the spatial distribution and density of voltage and ligand-gated channels. It is likely that, in vivo, most neurons in the circuit, despite variations in intrinsic membrane properties, are conditional output neurons equipped with the versatility of switching between output modes under appropriate conditions. Bursting mode may be used to boost the gain of neural signaling of important or novel events by enhancing transmitter release and enhancing dendritic depolarization, thereby increasing synaptic potentiation. Conversely, single spiking mode may be used to dampen neuronal signaling and may be associated with habituation to unimportant events. Mode switching may provide flexibility to the circuit allowing different sets of neurons to conditionally code for the various aspects of reward-related memory and behavior.