Pedunculopontine Glutamatergic Input to Substantia Nigra Pars Compacta Dopamine Neurons

Daniel James Galtieri

doi:https://doi.org/10.21985/N2TQ9M

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Pedunculopontine Glutamatergic Input to Substantia Nigra Pars Compacta Dopamine Neurons

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In vivo, substantia nigra pars compacta (SNc) dopaminergic neurons exhibit three spiking patterns – irregular, regular, and bursting. These distinct modes of activity are thought to underlie the different roles that dopamine (DA) plays in target structures within the basal ganglia. In particular, burst spiking in SNc DA neurons is thought to be a key signaling event in the circuitry controlling goal-directed behavior. The spontaneous transitions from single-spike mode to burst-spiking observed in vivo are lost, however, in ex vivo brain slices. Rather, a regular 1-4 Hz firing modes dominates SNc neuron activity in in vitro preparations. This change has been attributed to the loss of afferent input to SNc cells that would otherwise be present in an intact animal. Synaptic glutamatergic activity is thought to be especially important for burst generation, with much of the literature focusing on the interaction between N-methyl-D-aspartate receptors (NMDARs) and the intrinsic oscillatory activity in SNc neurons as a mechanism that promotes burst firing. To date, however, the role of specific neural networks in shaping spike patterning in SNc DA neurons has gone largely unstudied, due in part to the inability to selectively activate different inputs to the SNc. To begin filling this gap, SNc glutamatergic synapses arising from pedunculopotine nucleus (PPN) neurons were characterized using a mixture of optical and electrophysiological approaches. We found that PPN glutamatergic synapses are made primarily on the soma and proximal dendritic tree of these cells, placing these inputs in an ideal location to influence spike generation. Indeed, optogenetic stimulation of PPN axons reliably evoked spiking in SNc DA neurons that was dependent upon AMPA receptors but not NMDA receptors. Moreover, burst stimulation of PPN axons was faithfully followed by SNc DA neurons, suggesting that PPN-evoked burst spiking of SNc neurons in vivo may not only be extrinsically triggered but extrinsically patterned as well.

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