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TRPV1 regulates excitatory innervation of oriens lacunosum moleculare (OLM) neurons in the hippocampus to affect synaptic plasticity

Joaquin Isaac Hurtado Zavala
Doctoral thesis
Date of Examination: 2016-04-13
Date of issue: 2017-01-11
Advisor: Dean, Camin Dr.
Referee: Dean, Camin Ph.D.
Referee: Heinrich, Ralf Prof. Dr.
Referee: Dresbach, Thomas Prof. Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-002B-7CFC-F

 

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Abstract

English

The transient receptor potential vanilloid channel 1 (TRPV1) is a non-selective ion channel capable of being activated by multiple factors such as noxious stimuli, heat (>42 °C), low pH and pungent agents. Due to its pivotal role in pain perception TRPV1 has extensively been studied in the context of nociception in sensory neurons. Although TRPV1 has been discovered in the hippocampus, the exact cellular and subcellular expression as well as the function of the channel is still subject of strong debate. Using multiple techniques our study confirms the functional expression of TRPV1 in hippocampal neurons and provides information about the localization of the receptor. We found that the expression of TRPV1 was upregulated by NGF and high neuronal activity. TRPV1 was highly expressed in reelin/somatostatin-positive interneurons of the oriens lacunosum moleculare (OLM) that concomitantly express NGF (that likely increases TRPV1 expression). TRPV1 promotes high excitatory innervation of OLM neurons; when activated the channel recruits more excitatory terminals but if the channel is blocked or removed OLM neurons receive substantially less excitatory input. Such impairment is reflected in a significant decrease in LTP in the Schaffer collateral pathway in the TRPV1 KO mouse. This deficit in LTP is bypassed when OLM neurons are activated with nicotine - which selectively activates only OLM neurons in the hippocampus. This demonstrates functionally that TRPV1 is specifically expressed in OLM neurons. We also report some drawbacks detected in the TRPV1 knockout and the TRPV1 cre/lox P reporter mouse, two commercially available mouse lines commonly used in the field. Our findings may encourage other researchers to be more cautious with conclusions drawn using these animals. Together this thesis sheds light on the role of TRPV1 in synaptic plasticity in the hippocampus.
Keywords: TRPV1; Hippocampus; Synaptic plasticity; Oriens lacunosum moleculare interneurons
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