Role of an excitatory preoptic-raphé pathway in febrile vasoconstriction of the rat's tail

Abstract

Heat dissipation from the rat's tail is reduced in response to cold and during fever. The sympathetic premotor neurons for this mechanism, located in the medullary raphé, are under tonic inhibitory control from the preoptic area. In parallel with the inhibitory pathway, an excitatory pathway from the rostromedial preoptic region (RMPO) to the medullary raphé mediates the vasoconstrictor response to cold skin. Whether this applies also to the tail vasoconstrictor response in fever is unknown. Single- or a few-unit tail sympathetic nerve activity (SNA) was recorded in urethane-anesthetized, artificially ventilated rats. Experimental fever was induced by PGE2 injected into the lateral cerebral ventricle (50 ng in 1.5 μl icv) or into the RMPO (0.2 ng in 60 nl); in both cases, there was a robust increase in tail SNA and a delayed rise in core temperature. Microinjection of glutamate receptor antagonist kynurenate (50 mM, 120 nl) into the medullary raphé completely reversed the tail SNA response to intracerebroventricular or RMPO PGE2 injection. Inhibiting RMPO neurons by microinjecting glycine (0.5 M, 60 nl) or the GABAA receptor agonist, muscimol (2 mM, 30-60 nl), reduced the tail SNA response to PGE2 injected into the same site by approximately half. Vehicle injections into the medullary raphé or RMPO were without effect. These results suggest that the tail vasoconstrictor response during experimental fever depends on a glutamatergic excitatory synaptic relay in the medullary raphé and that an excitatory output signal from the RMPO contributes to the tail vasoconstrictor response during fever.

The median preoptic nucleus: front and centre for the regulation of body fluid, sodium, temperature, sleep and cardiovascular homeostasis

“…As a result, we have suggested that as well as the inhibitory output from MnPO, there are direct excitatory glutamatergic projections from MnPO to medullary raphé (possibly those excited by cold skin mentioned above) and that these projection neurones normally receive an inhibitory input from GABAergic interneurones within the MnPO that express EP3 receptors; thus during fever PGE2 would cause a disinhibition of the excitatory output from MnPO to medullary raphé to facilitate a fever (Tanaka et al . ).…”

Central neural control of thermoregulation and brown adipose tissue

“…Consistent with this model, L- glutamate injections into the POA, electrical stimulation of the POA and preoptic warming each elicit vasodilation in the rat paw and the rat tail (Zhang et al, 1995). Injection of PGE 2 or GABA into the POA increases CVC SNA (Tanaka et al, 2005; Rathner et al, 2008; Tanaka et al, 2009; Tanaka et al, 2013). Transection of the neuraxis immediately caudal to the POA increases CVC outflow (Rathner et al, 2008).…”

“…Transection of the neuraxis immediately caudal to the POA increases CVC outflow (Rathner et al, 2008). The MnPO contains cold-activated neurons that project to the rRPa and inhibition of neuronal discharge in the MnPO inhibits cold-and PGE 2 -activated increases in CVC (Tanaka et al, 2011; Tanaka et al, 2013). Following the increase in CVC SNA after transection of the neuraxis immediately caudal to the POA, subsequent brain transections caudal to the DMH, but rostral to the rRPa, do not significantly reduce CVC outflow and injection of muscimol into DMH does not affect either spontaneous, thermally-sensitive, CVC neuronal discharge, or that evoked by injection of PGE 2 into the POA (Rathner et al, 2008).…”

“…Indeed, the data of Tanaka and colleagues support a circuit for control of CVC with connections between both MnPO and MPA, and rRPa that parallels that proposed above with potential connections between both MnPO and MPA, and DMH/DA for the control of thermogenesis. PGE 2 -mediated inhibition of CVC inhibitory POA projection neurons, potentially those in the MnPO, contributes to the activation of CVC sympathetic premotor neurons during fever (Tanaka et al, 2013). The demonstration that POA contains GABAergic neurons that express EP3 receptors for PGE 2 and project to the rRPa (Nakamura et al, 2002), and that these are distinct from those EP3-expressing POA neurons that project to the DMH (Nakamura et al, 2009) provides a potential anatomical substrate for this marked difference between the hypothalamic regulation of CVC and that of thermogenic effectors.…”

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

“…Other work suggests that the glutamatergic MnPO inputs to the dorsal hypothalamic area (DHA) and raphe pallidus (RPa) promote hyperthermia in response to injections of pyrogenic agents into the preoptic area (Madden & Morrison, ; Tanaka et al . , ). Also, it was recently reported that stimulating a population of neurons that express the neuropeptide pituitary adenylate cyclase‐activating polypeptide (PACAP) or the growth factor brain‐derived neurotrophic factor (BDNF) in the ‘ventromedial preoptic area’ (equivalent to the ventral part of the MnPO) produces hypothermia, and ∼70% of these neurons were GABAergic (Tan et al .…”