Transient activation of specific neurons in mice by selective expression of the capsaicin receptor

Abstract

The ability to control the electrical activity of a neuronal subtype is a valuable tool in deciphering the role of discreet cell populations in complex neural circuits. Recent techniques that allow remote control of neurons are either labor intensive and invasive or indirectly coupled to neural electrical potential with low temporal resolution. Here we show the rapid, reversible and direct activation of genetically identified neuronal subpopulations by generating two inducible transgenic mouse models. Confined expression of the capsaicin receptor, TRPV1, allows cell-specific activation after peripheral or oral delivery of ligand in freely moving mice. Capsaicin-induced activation of dopaminergic or serotonergic neurons reversibly alters both physiological and behavioural responses within minutes, and lasts ~10 min. These models showcase a robust and remotely controllable genetic tool that modulates a distinct cell population without the need for invasive and labour-intensive approaches.

Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding

“…We performed a series of control experiments to confirm that expression of Trpv1 was restricted to Agrp neurons in the arcuate nucleus and not in off-target cells ( Figure S1 and Experimental Procedures). Trpv1 is a cation channel that is activated by the exogenous agonist capsaicin (Caterina et al, 1997) in a rapid and reversible manner (Güler et al, 2012). Slice whole-cell recordings showed that capsaicin increased the firing rate of Agrp neurons ( Figure 2C).…”

“…On the other hand, DREADD can be used to activate Agrp neurons by peripherally injecting receptor-ligand with robust induction of food intake (Krashes et al, 2011) but with more coarse kinetics . We used transgenic mice that conditionally express Trpv1 in Cre-expressing cells (Arenkiel et al, 2008;Güler et al, 2012) (R26-LSL-Trpv1; Figure 2B) to selectively introduce Trpv1 in Agrp neurons. By backcrossing these mice (R26-LSL-Trpv1) to a Trpv1 knockout background and then to Agrp-Cre mice, we generated animals that express Trpv1 exclusively in the Agrp neurons (hereafter, Agrp-Trpv1 mice; Figures 2B and S1).…”

Palatability Can Drive Feeding Independent of AgRP Neurons

“…AgRP DTR mice were put on a genetic background in which activation of dopamine neurons is mediated through the restricted expression of Trpv1, the capsaicin-receptor, in dopamine neurons; referred to as AgRP DTR ; DAT TRPV1 mice, see Figure 3A (Guler et al, 2012). Adult AgRP DTR ; DAT TRPV1 mice were presented with a palatable high-fat diet and the consequence of AgRP neuron ablation was evaluated in the presence or absence of capsaicin in the drinking water ( Figure 3C,3D).…”

“…(See also Figure S2). (Guler et al, 2012)) were crossed to Agrp DTR/+ mice (Luquet et al, 2005) on the C57Bl/6 background to generate AgRP DTR .…”

Immunoreactivity of arcuate nucleus astrocytes in rats after intragastric administration of habanero peppers (Capsicum Chinese Jacq.)

“…(Simone et al 1998). CAP may be transported via the blood-brain barrier (BBB), although the mechanism of the transport is not known (Güler et al 2012).…”