Scientific Evidence, Neuromythographic Reinterpretation

Scientific Evidence, Neuromythographic Reinterpretation

One of the challenges in getting a holistic view of the neuroscience literature is that there is "evidence" presented for just about every psychological concept being implemented by every brain part. Combined with the peer review process, this has created a "race to the highest abstraction" that incentivizes weak claims like a brain part is 'involved in memory' or 'contributes to flexible behaviors' in 'different contexts'.

As a result, if you are looking to invalidate the neuromythography archetypes, there is a plethora of evidence to cherry pick from that any given brain part "is also involved in" processes unrelated to the apparent symbolism of the archetype.

In our neuromythographic model, we assign the archetype Jyestha to the serotonin 5-HT2C receptor. Jyestha is the Hindu goddess of adversity and misfortune. She may seem like an odd goddess to be associated with serotonin.

The 5-HT2C receptor is interesting first because it tends to be localized to the neuron's flagellum. (Yes, many animal cells retain the flagellum of their choanoflagellate ancestors, and use them to circulate fluid around by beating in unison.) Another interesting thing is its gene is located on the X chromosome, so females have two copies of it while males only have one. The receptor's activation indirectly suppresses the release of motivating dopamine and arousing noradrenaline. The receptor is blamed for the negative side effects of some serotonin-promoting antidepressants, such as anxiety; some antidepressants specifically block 5-HT2C. Increased expression of the 5-HT2C receptor by neurons, independent of their activation by natural serotonin or drugs, creates negative emotional states.

The reason we assign 5-HT2C to Jyestha is its association with negative emotion and attitude. We chose a female bad attitude archetype partly because of its location on the X chromosome, but also because females seem to be more sensitive to it overall. A number of antidepressants target it. Here are some study significance blurbs from our neuromemex to support this archetype:

  • Knocking out 5-HT2C facilitated fear extinction by promoting a DRNc to BNSTad pathway.
  • In alcoholic male mice, DRN serotonin to 5-HT2C NAc dynorphin projections prevented dopamine response to social interactions.
  • In reversal learning, 5-HT2a antagonist slowed learning and increased incorrect responses during reversal execution, while antagonizing 5-HT2C improved reversal learning and responses.
  • Prozac may inhibit 5-HT2C receptors on astrocytes.
  • BNSTad 5-HT2c receptors promoted fear memory in females only.
  • Exercise reduces anxiety by reducing BNST 5-HT2C receptors.
  • Particular variants in 5-HT2C receptor caused obesity and bad behavior.
  • 5-HT2C KO mice had enhanced fear extinction due to elevated DRN-BNSTad circuit activity.
  • 5-HT2c agonists put zebrafish in a skittish mood, antagonists made dominant fish bolder but put subordinate fish in an even more skittish mood.
  • Reactivity to stressed others involves posterior insula 5-HT2C.
  • Activation of BLA 5-HT2C receptors mediated anxiety in response to uncontrollable stressors.
  • Blocking 5-HT2a receptors prevented conditioned defeat response acquisition. Activating 5-HT2c receptors promoted conditioned defeat response.

5-HT2C in Memory

Along comes a study:

Neural circuits expressing the serotonin 2C receptor regulate memory in mice and humans

The researchers sought to determine the involvement of 5-HT2C in memory. Memory, as a concept, seems pretty straightforward, but any process that has a cause and effect relationship between a past event and the future exhibits some sense of "memory".

In this case, the test of memory was a battery of standard punishments on mice who had their 5-HT2C receptors either degraded in function, blocked by drug antagonists, or stimulated by drug agonists.

  • In the water maze test in which rats must find a submerged platform, 5-HT2C-impaired mice learned the same as controls, but were less urgent in getting to the platform in later trials.
  • Male 5-HT2C-impaired mice froze less when hearing a tone associated with a foot shock.
  • 5-HT2C-impaired mice had the same responses to their feet being burned by a hot plate as control mice.
  • Activating 5-HT2C in the hippocampal CA1 region with a drug called lorcaserin improved performance in these tests, while blocking it degraded performance.

The researchers concluded:

[...] we report that human LOF HTR2C mutations are associated with learning and memory deficits.

This leads to the question, if 5-HT2C is a negative vibe, how does this account for this memory finding? One answer lies in the nature of the experiments: dropping mice into unpleasant situations, such as a pool, foot shock, or hot plate, is likely to elicit negative emotion. If one were to selectively impair this negative emotion "channel" to the hippocampus, we might expect it to mute the magnitude of effect on memory storage and recall. What we call memory in this case is downstream of the emotional content.

The neuromythographic archetype establishes a parallel system of sense-making around neuroscience to common every-day words and the jargon of cognitive science. They can all coexist, and provide alternative points of view.

About the author
Steven Florek

Steven Florek

Steven Florek is the creator of neuromythography and founder of Neuromemex.

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