fischer-update-2017

https://www.frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2017.00484/full

Fischer and Ullsperger review a variety of experiments showing that serotonin and dopamine interact in the reward system, such that combined they are more than the sum of their parts.

A number of interesting points stood out to me:

• serotoninergic neurons in the DRN often co-release glutamate
• most serotoninergic input in the forebrain comes from the DRN
• SSRIs may reduce the co-release of glutamate from serotoninergic neurons (iiiinteresting…)
• the regions that project to DRN 5HT neurons (but not MRN) are similar to those that project to VTA DA neurons.
• lateral habenula has been suggested to mediate aversive signals to both.
• "An influential hypothesis holds that 5-HT controls behavioral inhibition in an aversive context (Soubrié, 1986)" This may well be worth looking into Re: learned helplessness
• 5HT is strongly involved in punishement processing (consistent with the un-learning idea)
• There is also evidence hat 5HT mediates reward processing
• 5HT receptor expression displays a rostral-caudal gradient, indicating particular importance for 5HT in higher functions
• many 5HT neurons also release glutamate
• Inputs to DRN 5HT and VTA DA neurons (but not MRN 5HT neurons) follows a similar pattern
• PFC and LHb both provide input to both
• stimulating PFC-DRN projecting neurons increases motivation in rats
• LHb has been proposed to mediate aversive signaling to VTA and DRN

These three seem to form a puzzling little trio, though the article doesn't frame them as such?

• LHb seems to mostly inhibit DRN 5HT release
• optogenetic silencing of DRN GABA neurons prevented the development of behavioral avoidance (could this be explained as passivity or helplessless?)
• pharmacologically inactivating LHb seems to reduce stress-related behaviors
• rodent studies have found that alterations in 5HT processing can affect either reward or punishment sensitivity depending on the type, strength, or duration of manipulation.
• DRN innervates VTA DA neurons with both glutamate and serotonin
• VTA GABAergically innervated DRN
• DRN does encode reward likelihood and magnitude
• SERT expressing DRN neurons respond to reward but not punishment
• optogenetic stimulation of Pet-1 neurons in DRN is reinforcing this was much less in mice lacking the vglut-3 gene, indicating an important role for glutamate co-release. (this might be due to the glutamate multiplicatively up-regulating the targeted neurons, thereby amplifying their effect on the network?)
• this was not replicated in a subsequent experiment. lol
• targeting SERT+ neurons did not have the same effect (could be due to effects of SERT+ targeting on serotoninergic functioning more generally)
• DRN innervates mesostriatal VTA neurons with mostly glutamate but also serotonin
• VTA innervates DRN with GABA

5HT has been strongly implicated in both reward and punishment processing.