Participation of TRPV1 receptors during aversive responses in rodents using optogenetics tools

Abstract

AbstractTRPV1 receptors (rTRPV1, transient Receptor Potential Vanilloid Type 1) are widely expressed in several areas of the central nervous system (CNS), such as prefrontal cortex and hippocampus. This suggests their involvement during emotional responses modulation. rTRPV1 activation by exogenous or endogenous compounds increase cellular activity, mostly thru glutamatergic and nitric oxide (NO) release. Several studies showed rTPV1 involvement in responses related to anxiety and fear. Pharmacologic or genetic inhibition of these receptors reduce fear and produce anxiolytic-like responses. However, the absence of techniques with temporal and spatial precision (i.e. optogenetic), no study so far was able to access a) in which phase of extinction process rTRPV1 are involved; b) in which neuronal subpopulation those receptors are located; and c) on which neural circuits rTRPV1 promotes its effects. To solve those questions, the present study aims to evaluate rTRPV1 role during different phases of fear conditioned protocol, use viral vectors for rhodopisns expression (ionic channels responsive to light stimulus) exclusively in glutamatergic vs GABAergic neurons expressing rTRPV1. Rats implanted with optrods - for optogenetic techniques and in vivo electrophysiological records - will be habituated and trained in cued fear conditioning. On the first day, an initially neutral tone will be paired with electrical footshocks (tone: 75dB, 30s; shock 0.5s, o.5mA). On the following day, animals will be re-exposed only to the tone (20 presentations), for extinction learning. After 24h, they will be re-exposed again to the tone (4 presentations), to test the extinction learning. Different groups will be exposed to optogenetic activation or inhibition of distinct rTRPV1-expressing neurons, during extinction learning and test. Freezing responses and electrophysiological changes will be evaluated before and after optogenetic manipulations. Keywords: rTRPV1, learned fear, optogenetic, glutamate, GABA