Repeated activation of preoptic area recipient neurons in posterior paraventricular nucleus mediates chronic heat-induced negative emotional valence and hyperarousal states

  1. Zhiping Cao
  2. Wing-Ho Yung  Is a corresponding author
  3. Ya Ke  Is a corresponding author
  1. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, China
  2. Department of Neuroscience, College of Biomedicine, City University of Hong Kong, China
7 figures and 2 additional files

Figures

Figure 1 with 3 supplements
Chronic heat exposure produces negative emotional valence and hyperarousal states but not depression-like behaviors.

(A) Experimental schematics. Mice (n=10 in each group) were divided into Control and Heat groups and conducted with chronic exposure to room temperature and heat conditions, respectively, followed …

Figure 1—figure supplement 1
The effect of chronic heat exposure on physiological states of mice and their motion activity during behavioral tests.

(A, B) Monitoring of body temperature of mice daily before heat exposure for both groups and statistical comparison (n=6 mice in each group, two-way repeated measures ANOVA with Sidak post hoc test; …

Figure 1—figure supplement 2
Mice did not exhibit obvious changes of emotional valence and arousal states the day after acute heat exposure.

(A, B) The heatmap of representative tracking trace examples in elevated plus maze (EPM) test and the time spent in the open arms (n=6 mice, Mann-Whitney unpaired two-tailed U test; U=8, p=0.132). (C…

Figure 1—video 1
Representative video showed the delivery of a 105 dB sound stimulus within 200 ms evoked an obvious body fluctuation in the chronic heat-exposed mouse.
Figure 2 with 2 supplements
Involvement of the hypothalamic preoptic area (POA) to posterior paraventricular thalamus (pPVT) projections.

(A) The strategy of virus injection followed by heat exposure-induced c-Fos staining (n=3 mice). (B) The representative microphotograph showed the expression of rabies virus in the pPVT regions. (C) …

Figure 2—figure supplement 1
Posterior paraventricular thalamus (pPVT) was strongly activated after single-time heat exposure.

(A) Experimental schematics. Mice (n≥3 in each group) were randomly assigned to the control and acute heat groups, followed by immunofluorescent staining and confocal imaging. (B) The representative …

Figure 2—figure supplement 2
Preoptic area (POA) recipient posterior paraventricular thalamus (pPVT) neurons were activated after heat exposure.

(A) Experimental schematics. Mice (n=3) were stereotaxically injected with AAV1-hSyn-Cre-EGFP in the POA and AAV9-Ef1a-Dio-ChR2-mCherry in the pPVT, followed by heat exposure and c-Fos staining. (B) …

Figure 3 with 3 supplements
Activity changes of preoptic area (POA) recipient posterior paraventricular thalamus (pPVT) neurons throughout chronic heat exposure.

(A) Experimental schematics. Mice (n=5) were stereotaxically injected with Cre-dependent GCaMP into the pPVT, followed by the implantation of optical fiber and chronic calcium recording. (B) …

Figure 3—figure supplement 1
The calcium activities of the preoptic area (POA) recipient posterior paraventricular thalamus (pPVT) neurons were stable within our experimental period.

(A, B) The representative trace (left panel) and the overview of calcium events (right panel) of the control group from day 1 and day 22. (C, D) The changes of frequency (paired, parametric, …

Figure 3—figure supplement 2
Optogenetic activation of preoptic area (POA) excitatory neuronal terminals within posterior paraventricular thalamus (pPVT) produced aversive emotional valence and increased pupil size in mice.

(A) Experimental schematics. Mice (n=10) were stereotaxically injected with AAV9-CaMKII-ChR2-mCherry in the POA, followed by the implantation of optical fiber in the pPVT. (B) Representative …

Figure 3—video 1
Representative video showed the enlargement of both the pupil and eye sizes of the head-fixed mouse during blue light stimulation of preoptic area (POA) excitatory terminals within posterior paraventricular thalamus (pPVT).
Preoptic area (POA) recipient posterior paraventricular thalamus (pPVT) neurons are sufficient and necessary for chronic heat exposure-induced negative emotional valence and hyperarousal states in mice.

(A) Experimental schematics. Mice (n=10 in each group) were stereotaxically injected with either AAV1-hSyn-EGFP or AAV9-Camk2a-ChR2-mCherry into the POA, followed by the implantation of optical …

Figure 5 with 1 supplement
Chronically activated preoptic area (POA) recipient posterior paraventricular thalamus (pPVT) neurons exhibited exaggerated response to stressful situations.

(A) Experimental schematics. Mice (n=5) were stereotaxically injected with AAV1-hSyn-Cre-EGFP in the POA and AAV9-hSyn-Flex-jGCaMP8F-WPRE in the pPVT, followed by the implantation of optical fiber …

Figure 5—figure supplement 1
Preoptic area (POA) recipient posterior paraventricular thalamus (pPVT) neurons did not exhibit obvious changes in calcium activities when mice performed pause and walked to open arms, or walked to closed arms in the elevated plus maze (EPM), or displayed fast running in a heat-exposure-unrelated chamber.

(A–C) Heatmap showed the changes of calcium activities of the POA recipient pPVT neurons when mice performed pause and walked toward the open arms in the pre (n=41 trials from 5 mice) and post heat …

Figure 6 with 1 supplement
Increased pre- and postsynaptic excitability of posterior paraventricular thalamus (pPVT) neurons but saturated circuitry neuroplasticity capacity following chronic heat exposure.

(A) Experimental schematics. In vitro brain slice recording was performed on mice from three groups (n=16 neurons from 3 mice in the room temperature group, n=20 neurons from 4 mice in the acute …

Figure 6—figure supplement 1
The effect of chronic heat exposure on intrinsic properties of posterior paraventricular thalamus (pPVT) neurons.

(A–F) The changes of half-width (Mann-Whitney unpaired two-tailed U test; U=58, p=0.8977), threshold (Mann-Whitney unpaired two-tailed U test; U=43, p=0.2703), peak amplitude (Mann-Whitney unpaired …

A working model of neural circuit mechanisms underlying preoptic area (POA) recipient posterior paraventricular thalamus (pPVT) neurons-mediated chronic heat exposure-induced negative emotional valence and hyperarousal states.

Different from acute heat exposure, chronic heat exposure-induced enhancement in excitatory inputs to pPVT and saturated neuroplasticity contributed to the increased membrane excitability underlie …

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