Median preoptic glutamatergic neurons promote thermoregulatory heat loss and water consumption in mice

Abstract

The median preoptic nucleus (MnPO) serves an important role in the integration of water/electrolyte homeostasis and thermoregulation, but we have a limited understanding these functions at a cellular level. Using Cre-Lox genetic targeting of Channelrhodospin 2 in VGluT2 transgenic mice, we examined the effect of glutamatergic MnPO neuron stimulation in freely behaving mice while monitoring drinking behaviour and core temperature. Stimulation produced a strong hypothermic response in 62% (13/21) of mice (core temperature: -4.6 ± 0.5°C, P = 0.001 vs. controls) caused by cutaneous vasodilatation. Stimulating glutamatergic MnPO neurons also produced robust drinking behaviour in 82% (18/22) of mice. Mice that drank during stimulation consumed 912 ± 163 μl (n = 8) during a 20 min trial in the dark phase, but markedly less during the light phase (421 ± 83 μl, P = 0.0025). Also, drinking during stimulation was inhibited as water was ingested, suggesting pre-systemic feedback gating of drinking. Both hypothermia and drinking during stimulation occurred in 50% of mice tested. Anatomical mapping of the stimulation sites showed that sites associated with hypothermia were more anteroventral than those associated with drinking, although there was substantial overlap. Thus, activation of separate but overlapping populations of glutamatergic MnPO neurons produces effects on drinking and autonomic thermoregulatory mechanisms, providing a structural basis for their frequently being coordinated (e.g. during hyperthermia).

Identifying roles for peptidergic signaling in mice

“…The preoptic area of the hypothalamus is the central control region for core body temperature (47). Glutamatergic (excitatory, Emx1-expressing) neurons drive peripheral dilatation and severe hypothermia (46), while GABAergic neurons have less effect (70). Excitatory neurons in the preoptic area express many amidated neuropeptides: PACAP, CCK, CRH, oxytocin, tachykinin1, and GnRH (47,71).…”

“…Since PAM expression is reduced to half in both excitatory and inhibitory neurons in Pam KO/+ mice, while Pam Emx1-cKO/cKO mice lack PAM expression only in excitatory neurons, a difference in their ability to maintain core body temperature was anticipated. Excitatory neurons in the median preoptic area of the hypothalamus promote peripheral dilatation and core heat loss and produce a number of amidated peptides, which strongly affect thermoregulation (46,47).…”

Role of the median preoptic nucleus in the autonomic response to heat-exposure

“…In a paper published in October in the Journal of Physiology, we used optogenetic stimulation to address the role of glutamatergic neurons in the MnPO in thermoregulation [2]. Our experiments showed that activation of glutamatergic MnPO neurons decreases core temperature substantially, an effect we attributed to cutaneous vasodilatation.…”

“…One possible route would be that direct projections from glutamatergic MnPO neurons to the DHA/DMH, and the medullary raphe and parapyramidal region, may represent inputs to local inhibitory neurons within these targets that modulate the activity of sympathoexcitatory output neurons [3]. Alternatively, inputs from glutamatergic MnPO neurons to inhibitory GABAergic neurons in the lateral preoptic area (LPO) [1][2][3][4][5] and the periaqueductal gray matter may result in inhibition of sympathoexcitatory pathways that conserve heat.…”

Neurons in the rat ventral lateral preoptic area are essential for the warm‐evoked inhibition of brown adipose tissue and shivering thermogenesis

“…If vLPO neurons do receive a warm thermoreceptor driven input, we postulate ( Figure 9) that this input would arise from warm-responsive neurons in MnPO that receive an input from neurons in LPBd. 41 Cutaneous warm thermoreceptors activate neurons in the LPBd which project to the MnPO, 41 warm exposure activates glutamatergic neurons in MnPO, 25,42 and vLPO receives projections from MnPO neurons. 40,43 Consistent with vLPO neurons receiving a glutamatergic drive from warm-sensitive POA neurons is the finding that blockade of glutamate receptors in the vLPO prevents the inhibition of BAT SNA and BAT thermogenesis evoked by artificial POA warming.…”