Synaptic control of rat magnocellular neurosecretory cells by warm-sensing neurons in the organum vasculosum lamina terminalis.

Increases in core body temperature cause secretion of vasopressin (vasopressin, antidiuretic hormone) to promote water reabsorption and blunt water losses incurred through homeostatic evaporative cooling. Subtypes of transient receptor potential vanilloid (Trpv) channels have been shown to contribute to the intrinsic regulation of vasopressin-releasing magnocellular neurosecretory cells (MNCs) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN). However, MNCs in vivo can also be excited by local heating of the adjacent preoptic area, indicating they receive thermosensory information from other areas. Here, we investigated whether neurons in the organum vasculosum lamina terminalis (OVLT) contribute to this process using in vitro electrophysiological approaches in male rats. We found that the majority of OVLT neurons are thermosensitive in the physiological range (36-39°C) and that this property is retained under conditions blocking synaptic transmission. A subset of these neurons could be antidromically activated by electrical stimulation in the SON. Whole cell recordings from SON MNCs revealed that heating significantly increases the rate of spontaneous excitatory postsynaptic currents (sEPCSs), and that this response is abolished by lesions targeting the OVLT, but not by bilateral lesions placed in the adjacent preoptic area. Finally, local heating of the OVLT caused a significant excitation of MNCs in the absence of temperature changes in the SON, and this effect was blocked by inhibitors of ionotropic glutamate receptors. These findings indicate that the OVLT serves as an important thermosensory nucleus and contributes to the activation of MNCs during physiological heating.

Dynamic and permissive roles of TRPV1 and TRPV4 channels for thermosensation in mouse supraoptic magnocellular neurosecretory neurons.

The transient receptor potential vanilloid 1 and 4 genes (trpv1, trpv4) encode temperature-sensitive cation channels hypothesized to mediate thermoresponses in mammalian cells. Although such channels were shown to participate in the peripheral detection of ambient temperature, the specific roles of these channels in central thermosensory neurons remain unclear. Here we report that the membrane potential and excitability of mouse magnocellular neurosecretory cells (MNCs) maintained at physiological temperature were lowered in an additive manner upon pharmacological blockade, or genetic deletion, of trpv1 and trpv4. However extracellular recordings from spontaneously active MNCs in situ showed that blockade or genetic deletion of trpv4 does not interfere with thermally induced changes in action potential firing, whereas loss of trpv1 abolished this phenotype. These findings indicate that channels encoded by trpv4 play a permissive role that contributes to basal electrical activity, but that trpv1 plays a dynamic role that is required for physiological thermosensation by MNCs.

Osmotic and thermal control of magnocellular neurosecretory neurons--role of an N-terminal variant of trpv1.

The release of vasopressin (antidiuretic hormone) plays a key role in the osmoregulatory response of mammals to changes in salt or water intake and in the rate of water loss through evaporation during thermoregulatory cooling. Previous work has shown that the hypothalamus encloses the sensory elements that modulate vasopressin release during systemic changes in fluid osmolality or body temperature. These responses depend in part on a synaptic regulation of vasopressin neurons by afferent inputs arising from osmosensory and thermosensory neurons in the preoptic area. However, recent studies in rats and mice have shown that vasopressin neurons in the supraoptic nucleus also display intrinsic osmosensory and thermosensory properties. Isolated vasopressin neurons exposed to increases in perfusate temperature or osmolality generate increases in non-selective cation channel activity that cause membrane depolarization and increase neuronal excitability. These channels are calcium-permeable and can be blocked by ruthenium red. Moreover, intrinsic responses to osmotic and thermal stimuli are absent in magnocellular neurosecretory cells isolated from mice lacking the transient receptor potential vanilloid-1 (trpv1) gene, which encodes the capsaicin receptor. Immunostaining of vasopressin-releasing neurons with anti-TRPV1 antibodies reveals the presence of amino acids present in the carboxy terminus of the protein, but not those lying in the amino terminal domain. Thus, magnocellular neurosecretory neurons appear to express an N-terminal variant of trpv1 which lacks sensitivity to capsaicin, but which enables osmosensing and thermosensing.

Epileptiform synchronization in the rat insular and perirhinal cortices in vitro.

The hippocampus plays a primary role in temporal lobe epilepsy, a common form of partial epilepsy in adults. Recent studies, however, indicate that extrahippocampal areas such as the perirhinal and insular cortices represent important participants in this epileptic disorder. By employing field potential recordings in the in vitro 4-aminopyridine model of temporal lobe epilepsy, we have investigated here the contribution of glutamatergic and GABAergic signaling to epileptiform activity in these structures. First, we provide evidence of epileptiform synchronicity between the perirhinal and insular cortices, and resolve some pharmacological and network mechanisms involved in sustaining the interictal- and ictal-like discharges recorded there. Second, we report that in the absence of ionotropic glutamatergic transmission, GABAergic networks produce synchronous potentials that spread between the perirhinal and insular cortices. Finally, we have established that such activity is modulated by activating micro-opioid receptors. Our findings support clinical and experimental evidence concerning the involvement of the perirhinal and insular cortex networks in temporal lobe epilepsy, and provide observations that may impact research focussing on the role of the insular cortex in nociception.