The Impact of Caffeine on Hippocampal Long-Term Potentiation

The Impact of Caffeine on Hippocampal Long-Term Potentiation

Daniel Jabr

Dr. Joel Voss of the Feinberg School of Medicine at Northwestern University presented a talk showing how transcranial stimulation to the brain resulted in an enhancement of precision memory recollection.

Specifically, Dr. Voss investigated a particular region of the Hippocampus, the hippocampal posterior-medial (HPM) network, and showed that several days of electromagnetic stimulation facilitated increased recollection of specific, random spatial stimuli, meaning those who received stimulation showed an increased ability to recall the position of random visual stimuli. This finding establishes the HPM to be involved in spatial recollection and recollection of specific visual stimuli.

Dr. Voss further implicates the hippocampus in memory processes and shows that particular regions of the hippocampus can lead to preferential recollection of specific stimuli. The hippocampus has long been known as the major neural substrate for memories. To current knowledge, long-term potentiation (LTP) is the cellular mechanism underlying memory formation. 2 regions in particular of the hippocampus, the dentate gyrus (DG) and the Cornu Ammonis 1 (CA1) regions have been strongly shown to undergo LTP. LTP occurs when neurons of the hippocampus (DG or CA1) experience a tetanus electrical stimulation, that is, a very high frequency stimulation, this causes the synapses between the neurons to strengthen. This strengthening is due to the increased number of glutamate receptors in the post-synaptic cell after tetanus stimulation, meaning the post-synaptic cell will be hypersensitive to the release of neurotransmitter by the presynaptic cell. This strengthening of the synapse by means of increased receptors has been shown to persist (Malenka et al. 2004) with time, as the concentration of the receptors is maintained by the cell due to increased gene expression, yielding increased synthesis of the glutamate receptor which localizes to the cell membrane strengthening the synapse and encoding memories.

Furthermore, the effects of drugs on the nervous system is well documented, with one drug in particular being extremely widespread and is consumed daily around the world. Caffeine is a known stimulant of the central nervous system, increasing alertness and decreasing drowsiness (Mclellan et al. 2016). Does caffeine intake have an effect on LTP?

Blaise et al. (2018) investigated the role of caffeine on hippocampal LTP in rats.10-week-old rats were given access to a reservoir of water for 3 weeks, where the experimental group rats had 1g/L injection of caffeine into their drinking water and the control group had access to only normal tap water, without caffeine. After 3 weeks, the rats in both groups received tetanus stimulation by electrodes projecting to the CA1 region of the hippocampus to induce LTP, while LTP induction in the neurons of the CA1 was measured by recording electrodes. Blaise et al. reported that rats treated with caffeine showed significantly reduced levels of LTP induction with respect to control rats that did not receive caffeine. Hence, those rats that drank caffeine showed less potentiation of the hippocampal neurons closely linked to memory recollection.

These results show that caffeine may negatively impact memory recollection. The researches did not conclude what mechanism may have caused this depression in LTP induction. However, this drop in LTP may be due to caffeine promoting alertness and decreasing sleep in the rats, where the decrease of LTP induction in the neurons is due to the lack of sleep.

Hence, caffeine may result in decreased memory recollection by interfering with LTP in the hippocampus. As caffeine is the most consumed drug in the world, this is a particularly interesting finding, and suggests that extended periods of caffeine consumption may be correlated with decreased LTP in hippocampal neurons. As such, drinking caffeine might result in poorer performance on cognitive tasks and memory retrieval, not something that society today would be excited to here as caffeine is the most consumed drug that prepares people, from students to construction workers, for the day. Furthermore, caffeine interferes with the normal sleep-wake cycle and inhibits sleep to some extent. Thus, caffeine might not be the wonder-drug that it seems, and may lead to decreased memory recollection.

Link to journal article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840440/

References:

Malenka, RC, Bear, MF. 2004. LTP and LTD: An Embarrassment of Riches. Neuron 44:5-21

McLellan, TM, Caldwell, JA, Lieberman HR. 2016. A review of caffeine's effects on cognitive, physical and occupational performance. Neurosci. Biobehav. Rev. 71:294–312. 

Blaise, JH, Park, JE, Bellas, NJ, Gitchell, TM, Phan, V. 2018. Caffeine consumption disrupts hippocampal long-term potentiation in freely behaving rats. Physiological Reports 6(5): e13632