Abstract
The paraventricular thalamic nucleus (PVT) is a part of epithalamus and sends outputs to emotion-related brain areas such as the medial prefrontal cortex, nucleus accumbens, and amygdala. Various functional roles of the PVT in emotion-related behaviors are drawing attention. Here, we investigated the effect of manipulation of PVT neurons on the firing patterns of medial prefrontal cortical (mPFC) neurons and depression-like behavior. Extracellular single-unit recordings revealed that acute activation of PVT neurons by hM3Dq, an activation type of designer receptors exclusively activated by designer drugs (DREADDs), and administration of clozapine N-oxide (CNO) caused firing rate changes in mPFC neurons. Moreover, chronic presynaptic inhibition in PVT neurons by tetanus toxin (TeTX) increased the proportion of interneurons among firing neurons in mPFC and shortened the immobility time in the forced swimming test, whereas long-term activation of PVT neurons by hM3Dq caused recurrent hypoactivity episodes. These findings suggest that PVT neurons regulate the excitation/inhibition balance in the mPFC and mood stability.
Highlights
The paraventricular thalamic nucleus (PVT) is a part of epithalamus and sends outputs to emotionrelated brain areas such as the medial prefrontal cortex, nucleus accumbens, and amygdala
To evaluate the effect of chronic presynaptic inhibition of PVT neurons, we compared the activity of medial prefrontal cortical (mPFC) neurons during baseline, the first 30 mins in each session, and found that the number of well-isolated units was decreased in the tetanus toxin (TeTX)-on condition, the proportion of interneurons in the units, was significantly higher (Fig. 1C(c))
The activities of mPFC pyramidal neurons in the TeTXoff conditions were altered by clozapine N-oxide (CNO) administration whereas that in interneurons in the TeTX-off conditions and in both cells in the TeTX-on conditions were not, suggesting that neuronal activity changes in the mPFC by PVT activation had been mediated by synaptic transmission from PVT neurons to mPFC neurons
Summary
The paraventricular thalamic nucleus (PVT) is a part of epithalamus and sends outputs to emotionrelated brain areas such as the medial prefrontal cortex, nucleus accumbens, and amygdala. We investigated the effect of manipulation of PVT neurons on the firing patterns of medial prefrontal cortical (mPFC) neurons and depression-like behavior. Chronic presynaptic inhibition in PVT neurons by tetanus toxin (TeTX) increased the proportion of interneurons among firing neurons in mPFC and shortened the immobility time in the forced swimming test, whereas long-term activation of PVT neurons by hM3Dq caused recurrent hypoactivity episodes. These findings suggest that PVT neurons regulate the excitation/inhibition balance in the mPFC and mood stability. Thereafter, we evaluated the effects of acute or long-term hM3Dqor hM4Di-, a Gi-coupled inhibitory DREADD, and TeTX-PVT manipulation on the behavior in the long-term measurements of spontaneous wheel-running activity, forced swimming test (FST) and tail suspension test (TST)
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