[How fear unfolds inside our brains]

[[Re...]]

The stress-induced mechanisms that cause our brain to produce feelings of fear in the absence of threats have been mostly a mystery. Now, neurobiologists at the University of California San Diego have identified the changes in brain biochemistry and mapped the neural circuitry that cause such a generalized fear experience. Their research, published in the journal Science on March 15, 2024, provides new insights... 

https://www.eurekalert.org/news-releases/1036938

I find this worth reading.

Please note that this is an experimental animal study. 

Edited March 15 by [Re...]
Removed part from the quote, my intentions are easily misunderstood.

[[Re...]]

Under the link I will paste here, you will see a small diagram detailing the function of this area, very roughly. I did not paste this here due to possible copyright issues. 

Serotonergic Pathways. In addition to the dorsal and median raphe nuclear complex, many serotonergic neurons are found in the reticular region of the lower brain stem, which is subdivided into caudal and rostral groups. [...]. 

https://www.researchgate.net/figure/Serotonergic-Pathways-In-addition-to-the-dorsal-and-median-raphe-nuclear-complex-many_fig3_349715173

[[Li...]]

Interesting animal study @[Re...].  I don’t know about you but if I were a mouse with an already sensitized nervous system, I would have concerns about the interventions used to ‘stop the production of generalized fear’:

 

• Prior to the experience of acute stress, they injected the dorsal raphe of the mice with an adeno-associated virus (AAV) to suppress the gene responsible for synthesis of GABA.
• Further, when mice were treated with the antidepressant fluoxetine (branded as Prozac) immediately after a stressful event, the transmitter switch and subsequent onset of generalized fear were prevented.

 

[[Re...]]

Thank you @[Li...]. Yes this is an experimental animal study. But I have been always wondering what could be actually happening on the level of molecular biology/neuroanatomy.

I found these lines quite interesting :

[Studying the brains of mice in an area known as the dorsal raphe (located in the brainstem), the researchers found that acute stress induced a switch in the chemical signals in the neurons, flipping from excitatory “glutamate” to inhibitory “GABA” neurotransmitters, which led to generalized fear responses.]. 

Here comes the speculation from my side, that this actual "flip" that is happening, is due to the rebound/ possible epigenetic alterations of these receptors caused by the cessation of benzodiazepines. ( I now that this is extremely complicated.)

The process of withdrawal results in excessive GABA (R) activity in the raphe nuclei => generalized fear responses, anxiety, irritability, cirkadian rythm disturbances, etc. are activated. (See the second article I posted.)

This (the role of the raphe nuclei) might clear why we experience the same syndrome when withdrawing from antidepressants, too, as the raphe nuclei are part of the serotonergic system as well. It is unclear what could have been happening to the 5-HT receptors, though. 

This is only interesting to me, and very speculative, I know.... I should have way deeper knowledge to discuss this topic properly, and I am not sure if even that would help. 

But I definitely had no idea that increased GABA activity in the brainstem results in a stress response discussed above. I found this interesting. 

[[Li...]]

My sense is we’re coming at this from different perspectives, @[Re...].  Both are valid!  I keyed in on the authors’ goal of developing ‘interventions’ (one assumes, pharmaceutical products) designed to ‘stop the production of generalized fear’.  You’re looking at it as a way to understand what happens during withdrawal from psychotropic drugs … speaking of which, Horowitz and Taylor (2024) have several sections on this topic I found interesting. 

 

[[Re...]]

I am well aware that this train of though does not match the previous ones.

Well, you never know 

[[WU...]]

1 hour ago, [[R...] said:

But I definitely had no idea that increased GABA activity in the brainstem results in a stress response

Happening in an unmeasurable split second so hard to determine which process happened first. If GABA activity increases then there must be stress, if stress increases then there must be elevated GABA.