3/23/2006

Dopamine: Before the Law

Dopamine (DA) has been proposed to underlie the process of reward learning, and specifically to play a critical role in the flow of information through the thalamo-cortical loops joining prefrontal cortex and basal ganglia. As the logic goes, phasic dopamine bursts from the ventral tegmental area (VTA) trigger the "gating" of information into this working memory loop, based on experience with what information has been rewarding to maintain previously.

In the most recent issue of PNAS, authors Lodge and Grace ask what afferent signals prompt the phasic DA firing in the first place. They showed that tonic input from the laterodorsal tegmental nucleus (LDTg) actually allows the VTA dopamine neurons to fire when they receive excitatory activation. This leads to the somewhat confusing conclusion that the "gating" function by VTA has its own "gate," provided by LDTg.

In vivo, VTA DA neurons usually show an irregular firing pattern of around 4 Hz (with a range of 2-10 Hz). Interestingly, when LDTg is activated, it appears to increase the number of VTA neurons that are firing, but not their firing rate or their firing pattern. Instead, LDTg activation allows burst firing to take place; with an inactivated LDTg, VTA shows a very regular "pacemaker" patterns, the same as is normally observed in vitro (but has not been observed in vivo). The authors conclude that "disruption within the LDTg or in its regulation by the PFC could be an underlying factor in the pathophysiology of major psychiatric disorders."

As an aside, I have a feeling that this isn't the last "gating of gating" type function we'll see. The microcircuitry linking inhibitory interneurons and DA neurons is incredibly complex, and they maintain very sophisticated regulatory firing patterns. It sort of feels like Kafka's "Before the Law," in which there are doors upon doors (or gates upon gates?) through which we pass before we'll really understand the mechanisms driving intelligent behavior.

Related Posts:
Models of Dopamine in Prefrontal Cortex
Visualizing Working Memory
Task Switching in Prefrontal Cortex

2 Comments:

Anonymous mccm said...

i just discovered your blog through postgenomic.. i did a couple posts on that Armitage story when it came out too.. looks like you will be a very good source of information since i find it so confusing to slog through those Grace lab papers.. linking to you now..

i'm a kafka fan too.. although to stick to the story we have to interrogate the gating of the VTA until we die and we never even get to look at the tegmentum.. hopefully the analogy doesn't apply..

3/24/2006 02:07:00 PM  
Blogger Chris Chatham said...

yeah, i hope it doesn't apply either. but something about "gating of gating" brought to mind "doors upon doors" and I couldn't shake the analogy to kafka!!!

thanks for linking, looks like your blog is really nice too. I'll link back..

3/25/2006 08:54:00 AM  

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