Written by: Jacinda Taggett
Edited by: Elena Bobric
When choosing a field of study to go into for my research, I was immediately drawn to the neuroscience of human memory and had very little explanation as to why. That was over five years ago, and over time I have been dealt with the curse that psychologists and neuroscientists bear.
In my past experience talking to aspiring scientists in these disciplines, they always say that they were initially drawn to their research question because of their own experiences (or a loved ones’ experience) with their field of study. I did not necessarily have this same personal motivation, but I will admit that my memory has declined since then.
There are plenty of factors that can possibly explain my memory issues, from living with bipolar disorder to obsessing over short-form social media content to being on medications that alter my brain chemistry. I guess upon reflection of these personal attributes, the question is “how do these factors impact my cognition?” The most likely potential answer is the neuromodulators associated, dopamine and norepinephrine.
Intro to neuromodulators
Neuromodulators are a subset of neurotransmitters, or simply “brain chemicals”, that influence the conduction of signals throughout neurons, primarily in a scatter or spread out way. Two examples of neuromodulators that have been associated with memory impairment or improvement are dopamine and norepinephrine.
Dopamine
Known as the “pleasure chemical” of the brain, dopamine has been shown to affect multiple aspects of living and cognition. From movement to thinking to even symptoms of psychosis, this molecule has a wide variety of purposes in our brains. If you ever want a fun crash course on the various symptoms of minimal dopamine to extreme levels of dopamine, I recommend watching Awakenings (1990) starring Robert De Niro and Robin Williams. If you were to watch this movie, you would see symptoms such as inability to move (minimal dopamine in the brain) and manic rambling (excess dopamine in the brain). On a similar note, it is worth mentioning that dopamine imbalances are associated with various disorders such as Parkinson’s Disease, schizophrenia, bipolar disorder, and ADHD… which all of these tend to have cognitive deficits as well. To better explain these cognitive deficits, dopamine’s role in memory has been studied for decades throughout differing clinical populations (Kourosh-Arami et al., 2023).
Norepinephrine
Norepinephrine, also called “noradrenaline”, is a lesser known neuromodulator by the general public. This chemical is associated with the “fight-or-flight” response of individuals, leading to feelings of alertness or arousal. Imbalances of norepinephrine have been associated with disorders of depression or anxiety, as well as problems with memory. Therefore, sometimes patients with depression will be given SNRIs (serotonin-norepinephrine reuptake inhibitors) to increase norepinephrine in the brain. However, someone with anxiety is not advised to be given this same medication due to their susceptibility to already having too much norepinephrine release during anxiety episodes. However, the role of norepinephrine in cognitive deficits is harder to explain, leading neuroscientists to use various methods as described below.
Utilizing Rodent Models for Reference
In order to determine neuromodulators’ role in memory, we have to look at rodent models as this is one of the few populations we can experimentally alter the activation of neurons in the brain. Throughout the research done on rodent models, we see that the part of the brain responsible for projecting norepinephrine and dopamine to other parts of the brain, the locus coeruleus (LC), can improve long-term memory. This enhancement of memory was seen when the neurons connecting the LC to the brain part responsible for memory, the hippocampus, are stimulated during learning (Wilmot et al., 2024).
Although we see these associations in rodents, the methods for studying norepinephrine and dopamine’s role on human memory can be more complex.
Neuromodulators and Human Memory
Dopaminergic Measures and Explanations
When utilizing neuroimaging tools such as (f)MRI, researchers are able to determine that reward circuitry and the way it interacts with the hippocampus or the prefrontal cortex to improve memory. For example, when using Diffusion Tensor Imaging (an MRI-based measure of connectivity in the brain) during a value-directed remembering task, researchers had seen that the pathways depositing dopamine to the prefrontal cortex was associated with better memory performance for rewarding stimuli (Reggente et al., 2018). Popular theories for findings like this suggest that dopaminergic neurons enhance memory through providing internal reward value to memories, stabilizing memories, and identifying novelty in memories (Knowlton & Castel, 2022).
Norepinephrinergic Measures and Explanations
Tools to study norepinephrine and cognition in humans often rely on pupil dilation, therefore using eye tracking devices in order to assess how much of this neurotransmitter is being released. A pupil dilation, neuromelanin and fMRI study had concluded that goal-directed remembering, especially those that are from arousing situations, is better predicted by norepinephrine release (Clewett et al., 2018). In other words, when someone is told to remember a scene or else they would lose money, their pupils would dilate (biomarker for norepinephrine release) and the regions of the brain necessary for analyzing scenes were activated, leading to better memory for the scene compared to other parts of the moment.
Many different models and theories have been proposed to explain why norepinephrine enhances memories, especially in emotional or salient contexts. Mainly, it is concluded that norepinephrine release increases long-term potentiation, a process in which connections between neurons that hold memories are strengthened, with every salient experience (Mather et al., 2016). Long-term potentiation is a process by which neuronal synapses are positively exciting each other frequently, allowing the memory associated with them to be easier to recall with every excitation. Since norepinephrine is an excitatory neuromodulator, then having the excess neurotransmitters during emotional or salient events can lead to stimulation of these neurons (Gelinas & Nguyen, 2007).
How can we improve our memory?
Once we consider how neuromodulators such as dopamine and norepinephrine improve memory in various contexts, the first question that comes to mind is “How is this useful for me?” Further research needs to be implemented to better understand whether these cognitive benefits can be used strategically (i.e., there are other cognitive processes that must occur in order for these benefits to happen) or pharmacologically (i.e., we can use dopaminergic and norepinephrinergic medications to improve memory). For a strategic approach, one can consider how their attention, curiosity, and motivation for learning information can have a positive influence on their long-term memory. Although this seems sound in concept, the actual practice of sustaining attention or piquing curiosity or feeling motivated can be hard to implement in practice.
Those that instead want a more long-term treatment plan for their cognitive functioning might want to consider an intervention such as Wellbutrin, a norepinephrine-dopamine reuptake inhibitor (NDRI), which has been shown to improve cognitive functioning in clinical populations such as those with Major Depressive Disorder (Soczynska et al., 2014). Although, a caveat to this approach is that the main line of clinical diagnoses for this drug are Major Depressive Disorder and Seasonal Affective Disorder, indicating that baseline levels of these neuromodulators might be lower in these studies’ samples.
Regardless of whichever approach becomes standardized practice in the years to come, we still need more research in this field of study. Without the basic science questions answered from cognitive neuroscientists and the pharmacological trials from clinical neuroscientists, we cannot truly understand how we will best improve human memory.
References
Clewett, D. V., Huang, R., Velasco, R., Lee, T.-H., & Mather, M. (2018). Locus Coeruleus Activity Strengthens Prioritized Memories Under Arousal. The Journal of Neuroscience, 38(6), 1558–1574. https://doi.org/10.1523/JNEUROSCI.2097-17.2017
Gelinas, J., & Nguyen, P. (2007). Neuromodulation of Hippocampal Synaptic Plasticity, Learning, and Memory by Noradrenaline. Central Nervous System Agents in Medicinal Chemistry, 7(1), 17–33. https://doi.org/10.2174/187152407780059196
Knowlton, B. J., & Castel, A. D. (2022). Memory and Reward-Based Learning: A Value-Directed Remembering Perspective. Annual Review of Psychology, 73(1), 25–52. https://doi.org/10.1146/annurev-psych-032921-050951
Kourosh-Arami, M., Komaki, A., & Zarrindast, M.-R. (2023). Dopamine as a Potential Target for Learning and Memory: Contributingto Related Neurological Disorders. CNS & Neurological Disorders - Drug Targets, 22(4), 558–576. https://doi.org/10.2174/1871527321666220418115503
Mather, M., Clewett, D., Sakaki, M., & Harley, C. W. (2016). Norepinephrine ignites local hotspots of neuronal excitation: How arousal amplifies selectivity in perception and memory. Behavioral and Brain Sciences, 39, e200. https://doi.org/10.1017/S0140525X15000667
Reggente, N., Cohen, M. S., Zheng, Z. S., Castel, A. D., Knowlton, B. J., & Rissman, J. (2018). Memory Recall for High Reward Value Items Correlates With Individual Differences in White Matter Pathways Associated With Reward Processing and Fronto-Temporal Communication. Frontiers in Human Neuroscience, 12, 241. https://doi.org/10.3389/fnhum.2018.00241
Soczynska, J. K., Ravindran, L. N., Styra, R., McIntyre, R. S., Cyriac, A., Manierka, M. S., & Kennedy, S. H. (2014). The effect of bupropion XL and escitalopram on memory and functional outcomes in adults with major depressive disorder: Results from a randomized controlled trial. Psychiatry Research, 220(1–2), 245–250. https://doi.org/10.1016/j.psychres.2014.06.053
Wilmot, J. H., Diniz, C. R., Crestani, A. P., Puhger, K. R., Roshgadol, J., Tian, L., & Wiltgen, B. J. (2024). Phasic locus coeruleus activity enhances trace fear conditioning by increasing dopamine release in the hippocampus. eLife, 12, RP91465. https://doi.org/10.7554/eLife.91465.3