Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum.

2 years ago

Summaries

2/0

In this extensive anatomical study Susan Haber et al trace in detail the reciprocal connections between the different striatal regions and the midbrain dopamine neurons that provide input to them. They first make an admirable effort to functionally divide the striatal regions (in primate) into limbic (VMS), associative (CS), and sensorimotor (DLS) by mapping the regions by the inputs from limbic corticies/amygdala/hippocampus, dlPFC, and motor/premotor regions respectively. They then did many anterograde, retrograde, and bidirectional tracer injections in various striatum and the midbrain sites. Among their many findings, the one that warranted great attention and a theoretical framework about network function was that for each successive striatal region moving in the ventromedial-dorsolateral direction their inputs to the midbrain had both overlap with where their own DA inputs originated and extended past the origin region in the ventral direction (moving inversely to the striatal axis) to exert influence on the midbrain neurons that would be sending input to the “next step up” in the striatum. They conjecture that the part of the inputs going back to the origin DA cells have direct synapses with the DA cells to provide feedback inhibition while the part of the inputs going to the adjacent midbrain area synapse with inhibitory interneurons thus disinhibiting the next set of DA cells. They dub this the “ascending spiral” that allows striatal regions to have influence on the regions just dorsolateral to them by modulating their dopamine inputs.

Praise

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I find this a fascinating hypothesis and I wonder if they could make some predictions about what kinds of future experimental electrophysiology or optogenetics results can help to support this idea. How would this circuit work in real time? Would we expect to see the each successive step in the spiral happening several milliseconds after the previous signal?

Re: Coolness

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Interesting! If you electrically stimulate at the beginning of the spiral, do you see a response at the end of the spiral at a time delay that's appropriate for such a roundabout path? (I can imagine lots of reasons why you *wouldn't* see the delay, even though the spiral hypothesis is right. But a positive result here would be informative and cool).

Re: Coolness

Criticism

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I wonder if they could have conjectured how this roundabout method of adjacent striatal zones to influence each other would interact with the more direct method of MSNs and interneurons within striatum communicating to adjacent areas via their interstriatal connections depending on the reach of their dendritic and axonal arbors.

Re: Rigor