Artstract created C. Geraci
Do you know someone with an anxiety disorder or do you, yourself, have one? Have you ever wondered what is going awry in the brain to make that happen? To understand this, we need to establish a baseline understanding on how memory formation and consolidation, which is the process of creating a permanent long-term memory, occur.
The Anatomy of the Limbic System
The limbic system is the primary part of the brain involved in memory formation and consolidation, and the primary structures within it are the basal ganglia, amygdala, and hippocampus. Each of these structures is portrayed in Figure 1 along with the types of memory they encode, but below each memory type is defined along with its corresponding brain structure.1
- Basal ganglia: procedural memory, which remembers how we certain perform tasks.
- Hippocampus: declarative or explicit memory, which involves remembering things like names, facts, etc.
- Amygdala: implicit & procedural memory, with implicit memory involving remembrance of things not outrightly spelled out but more likely felt, like emotions.1
Figure 1. Illustrates the limbic system’s structures and what types of memory each is involved in creating.1
The Hippocampal Formation, Specifically the Dentate Gyrus
Figure 2. Illustrates the anatomy of the dentate gyrus in the hippocampus formation.2
The dentate gyrus (DG) is part of something called hippocampal formation, which also encompasses the hippocampus (see Figure 2). It is made of multiple types of cells and is involved in the formation of episodic memory and exploration of new environments.
The three types of cells are dentate granule cells, which are excitatory and use glutamate as their primary neurotransmitter, inhibitory dentate pyramidal basket cells, and excitatory, unmyelinated granule cells called mossy fibers. Mossy fibers synapse onto the CA3 region of the hippocampus, which contains neurons that can then send excitatory signals to the CA1 region of the hippocampus. However, all these play a role in either exciting or inhibiting hippocampal neuron firing.2
The Pathway of Memory Formation, Learning, & Memory Consolidation
Figure 3. Illustrates the different lobes of the cerebral cortex and the cerebellum’s role in memory formation.1
Also involved in memory formation are the cerebral cortex and cerebellum, and for information on the cerebellum, click here. The cerebral cortex is where certain memories are stored after the hippocampus has consolidated them, with each lobe corresponding to a different type of memory stored there, as can be seen in Figure 3 above.1
Compiling all the above information, we can create the below pathway that illustrates how memory formation and learning occurs:
- Learning begins when sensory signals are transcribed in the cerebral cortex
- These signals are transmitted to either the hippocampus, amygdala, and/or dentate gyrus. If to the amygdala or dentate gyrus, they send signals the correlate to how and if the memory is processed by the hippocampus
- If the signal is strong or repeated, a long-term memory is consolidated by the hippocampus
- The memory is wired back to the cerebral cortex for storage.3
And when you think about it, when you are able to recall how to do something or a fact, that is the outward sign that you’ve accurately consolidated a memory. Aka, you’ve learned something!
A Pathway to Anxiety
But in anxiety disorders, such as PTSD or generalized anxiety disorder, some part of this memory formation, learning, and/or consolidation process is disrupted. One study investigated why this is and discovered elevated levels of a dual histone mark called H3S10p-K14ac. This histone mark was found on the promoter regions of the fos and egr1 genes. Essentially, one part of these genes was phosphorylated while another part was acetylated, and what this caused was increased transcription of the fos and egr1 genes, leading to increased anxiety.4
Interestingly, the genes with the H3S10p-K14ac dual histone mark were only present in dentate neurons, and when GABAergic inhibitory signals were administered to the DG to block H3S10p-K14ac histone marks from building, symptoms of anxiety decreased. As established earlier, the DG plays a role in telling the hippocampus whether to consolidate a memory or not, so the fact that inhibition of block H3S10p-K14ac histone marks in the DG led to decreased anxiety tells us that something anxiety disorders disrupt the flow of information from the DG to the hippocampus. This makes it so memories cannot be correctly stored in the cerebral cortex, perhaps making them more present in a person’s mind, therefore causing them to feel anxiety in situations where if their memory had been correctly consolidated, they would not be making anxious associations with previously psychologically stressful experiences.4 For more information on how the dual histone H3S10p-K14ac mark forms following psychologically stressful events, click here.
Conclusion
Overall, there is a typical pathway by which learning and memory formation occur within the brain, with the limbic system and the cerebral cortex playing a large role in securely storing memories so that we can recall them at appropriate times. But anxiety disorders involve a disruption in this pathway, allowing memories and their associated emotions, like fear, to be at the forefront of someone’s mind at times they wouldn’t normally. Therefore, further research should be done to study what factors are disrupted in each anxiety disorder so that this information can be used to target the root biochemical cause of each disorder.
Footnotes:
1https://www.youtube.com/watch?v=yepwx67_UkM
2Shahid, Shahab. “Dentate gyrus.” Kenhub. 2023. https://www.kenhub.com/en/library/anatomy/dentate-gyrus#
3https://www.youtube.com/watch?v=4Hm08ksPtMo
4Reul, M.H.M. Johannes. “Making memories of stressful events: a journey along epigenetic, gene transcription, and signaling pathways.” Frontiers in Psychiatry, vol. 5, no. 5, 2014, doi: 10.3389/fpsyt.2014.00005
