The Effects of Dopaminergic Modulation on Afferent Input Integration in the Ventral Striatal Medium Spiny Neuron

Utilizing a highly detailed model of the medium spiny neuron and a small network of these cells, in this chapter we analyze the processing of synaptic inputs by the striatum and the modulation of this processing via D1 and D2 activation. Computational models such as the one presented here allow for an examination of the cell or network’s response of an identical set of inputs under various sets of intrinsic and synaptic modulations. In the single cell model, D1 modulation leads to an increase in the output of the cell at all input frequencies, whereas D2 modulation led to a significant reduction at all of the synaptic input frequencies. These results are generally supportive of the ideas of the Albin-DeLong model, which originally suggested that there is segregation of the indirect and direct pathways in the dorsal striatum, and that D1 is excitatory and D2 is inhibitory. What has previously not been fully appreciated is the contribution and interaction of the synaptic modulations and the intrinsic modulations via DA to elicit this effect. Our model indicates that changes in the NMDA:AMPA ratio during pathological states may have an impact on normal synaptic input processing, and that lateral inhibition may have a greater effect at the network level than assumed from recent in vitro results. Elucidation of the role of dopaminergic modulation on network level interactions will play a crucial role in our understanding of information processing in the striatum.