Transgene-free magnetothermal neurostimulation and the induction
of fear behaviors
Motivated by the highly efficient activation of neurons in the
CeA regions of transgenic TRPV1-expressing mice by the FVIOs, we further
explored the possibility of applying this nanoheater to activate
endogenous TRPV1-expressing neurons in transgene-free mice. As
previously reported, TRPV1 endogenously expressed on neurons in
the CeA of mice[56-57], we also confirmed the
endogenous expression of TRPV1 (red) on cells in the CeA regions of mice
using immunohistochemical methods, as shown in Fig. 8a and 8b. Then, the
FVIOs were modified with anti-TRPV1 antibodies to target endogenous
TRPV1 in the CeA regions of transgene-free mice. Different doses of
anti-TRPV1-FVIOs were injected into the CeA regions of these mice, and
the fear behavioral response induced by FVIO-mediated magnetothermal
stimulation was investigated under AMF exposure (20 mT, 275 kHz). The
results verified that the anti-TRPV1-FVIOs elicited freezing behaviors
in the mice at a minimum dose of 0.28 μg (Figure 8c). This
transgene-free magnetothermal neurostimulation strategy avoids possible
side effects arising from the overexpression of exogenous TRPV1 and gene
delivery with viral vectors, which further improves the biosafety and
expands the scope of magnetothermal neurostimulation
applications[11, 58].