TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus

Abstract

TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, and has been extensively studied in nociception of sensory neurons. However, the location and function of TRPV1 in the hippocampus is debated. We found that TRPV1 is expressed in oriens-lacunosum-moleculare (OLM) interneurons in the hippocampus, and promotes excitatory innervation. TRPV1 knockout mice have reduced glutamatergic innervation of OLM neurons. When activated by capsaicin, TRPV1 recruits more glutamatergic, but not GABAergic, terminals to OLM neurons in vitro. When TRPV1 is blocked, glutamatergic input to OLM neurons is dramatically reduced. Heterologous expression of TRPV1 also increases excitatory innervation. Moreover, TRPV1 knockouts have reduced Schaffer collateral LTP, which is rescued by activating OLM neurons with nicotine—via α2β2-containing nicotinic receptors—to bypass innervation defects. Our results reveal a synaptogenic function of TRPV1 in a specific interneuron population in the hippocampus, where it is important for gating hippocampal plasticity.

Expression of TRPV1 channels by Cajal‐Retzius cells and layer‐specific modulation of synaptic transmission by capsaicin in the mouse hippocampus

“…2016; Hurtado‐Zavala et al . 2017; see also review by Kauer & Gibson, ). Thus, application of capsaicin might trigger some form of network activity, which would result, indirectly, in responses in CRs.…”

“…More recent work has also proposed that TRPV1 expressed by hippocampal O‐LM interneurons of stratum oriens promotes the formation of excitatory synapses on this cell type (Hurtado‐Zavala et al . 2017). Notably, the impact of TRPV1 activation on the microcircuits of the molecular layers innervated by CRs (either in the dentate gyrus or on the Cornu Ammonis) has not been examined yet.…”

“…In fact, while Cavanaugh et al (2011) have suggested that CRs are the only hippocampal neuronal type expressing TRPV1, other studies indicate a more widespread expression, including several other neuronal types (i.e. pyramidal cells, GABAergic interneurons, and granule cells; see Toth et al 2005;Cristino et al 2006;Gibson et al 2008;Chávez et al 2010Chávez et al , 2014Puente et al 2015;Canduela et al 2015;Lee et al 2015;Eguchi et al 2016;Hurtado-Zavala et al 2017; see also review by Kauer & Gibson, 2009). Thus, application of capsaicin might trigger some form of network activity, which would result, indirectly, in responses in CRs.…”

“…In the hippocampus proper, Gibson et al (2008) have reported that the stimulation of TRPV1 located on the presynaptic terminals of the Schaffer collaterals decreases evoked excitatory synaptic transmission on stratum radiatum interneurons, and induces long-term depression. More recent work has also proposed that TRPV1 expressed by hippocampal O-LM interneurons of stratum oriens promotes the formation of excitatory synapses on this cell type (Hurtado-Zavala et al 2017 or on the Cornu Ammonis) has not been examined yet. Therefore, given our evidence that CRs express functional TRPV1, we decided to test the prediction that the pharmacological stimulation of slices with capsaicin would produce changes in synaptic activity of CR targets, such as GABAergic interneurons of the molecular layers (Figs 10, 11, 12 and 13).…”

“…Although the acute effects of TRPV1 stimulation on synaptic transmission were not studied, Hurtado‐Zavala et al . (2017) have recently reported that TRPV1 activation promotes the development of excitatory innervation of O‐LM interneurons. Similar to the interneurons recorded in this work, O‐LM interneurons target the molecular layers of the hippocampus proper, i.e.…”