Jared Weed and Dr. Jeffrey Edwards, PDBIO

Introduction

The hippocampus is the area of the brain where long-term declarative memories are formed. Synaptic plasticity, the long-term strengthening or weakening of the synapse (the connection between two neurons), is the proposed cellular mechanism for the process of memory formation. The two types of synaptic plasticity are long-term potentiation (LTP), in which a synapse becomes strengthened; and long-term depression (LTD), in which a synapse becomes weakened.

Synaptic plasticity can be mediated by many different cellular pathways, but in Dr. Edwards’ lab, we focus on how the activity of transient receptor potential vanilloid 1 (TRPV1) receptors mediates synaptic plasticity. TRPV1 receptors are activated by low pH, high temperature, capsaicin (the molecule responsible for the pungent effects of hot peppers), and endogenous ligands including anandamide. TRPV1 receptors are known for their role in pain pathways in the peripheral nervous system, but in recent years they have been shown to exert influences in the central nervous system. They are known to mediate LTD on interneurons in the hippocampus (Gibson et al., 2008) and on neurons in the superior colliculus (Maione et al., 2009). Our research has focused on how TRPV1 can mediate overall LTP in Area CA1 of the hippocampus.

Methods

In Dr. Edwards’ lab, we study synaptic plasticity in area CA1 of hippocampal slices using electrophysiological recording equipment. With each experiment, we attempt to induce either LTP (using high frequency stimulation) or LTD (using low frequency stimulation) by stimulating Schaffer collateral axons and recording responses in area CA1 (Figure 1). In different experiments, we were able to activate TRPV1 receptors using capsaicin and resiniferatoxin. In some experiments, we blocked transmission of GABAergic interneurons by using the drugs picrotoxin or bicuculline. All experiments were performed on rats aged between 16 and 29 days.

Results

I contributed to the results that our lab published in Neuropharmacology this year (Bennion et al., 2011). Overall, the paper showed that TRPV1 directly modulates plasticity on CA1 interneuron synapses, but not CA1 pyramidal cell synapses (See Figure 2 for a model derived from our results). We knew that 1μM capsaicin induced LTP at CA1 synapses, but we found in the literature that low concentrations may produce LTD. To ensure this was not the case, I performed LTP experiments using 100μM Capsaicin to show that this low concentration does not cause LTD. I also performed experiments using bicuculline (GABA antagonist) and resiniferatoxin (TRPV1 agonist) to show that blocking the influence of interneurons blocks the enhanced TRPV1-mediated LTP.

Conclusion

We found it curious that TRPV1 receptors were present on Schaffer collateral axons at CA1 pyramidal cell synapses, but were not present at CA1 interneuron synapses. To investigate this further, Dr. Edwards’ undergraduates will investigate the developmental differences in plasticity by performing experiments on rats younger than 16 days. To help members of the lab understand what is known about developmental effects on plasticity in the hippocampus, I wrote a review paper for the lab.

I will begin the neuroscience master’s program at BYU in January 2012, and will continue researching with Dr. Edwards. For my master’s thesis, I will not continue in the same direction as the undergraduates in the lab. Instead, I will independently investigate the plasticity properties of an uncharacterized type of interneuron that exists in the pyramidal cell layer in Area CA1 of the rodent hippocampus.

References

• Bennion, D., Jensen, T., Walther, C., Hamblin, J., Wallmann, A., Couch, J., . . . Edwards, J. G. (2011). Transient receptor potential vanilloid 1 agonists modulate hippocampal CA1 LTP via the GABAergic system. Neuropharmacology, 61(4), 730-738.
• Gibson, H. E., Edwards, J. G., Page, R. S., Van Hook, M. J., & Kauer, J. A. (2008). TRPV1 channels mediate long-term depression at synapses on hippocampal interneurons. Neuron, 57(5), 746-759.
• Maione, S., Cristino, L., Migliozzi, A.L., Georgiou, A.L., Starowicz, K., Salt, T.E., Di Marzo, V. (2009). TRPV1 channels control synaptic plasticity in the developing superior colliculus. Journal of Physiology, 587(11), 2521-2535.