α₂-Adrenoceptor-Mediated Presynaptic Modulation of GABAergic Transmission in Mechanically Dissociated Rat Ventrolateral Preoptic Neurons

Abstract

Matsuo, Shin-ichiro, Il-Sung Jang, Junichi Nabekura, and Norio Akaike. ␣ 2 -Adrenoceptor-mediated presynaptic modulation of GABAergic transmission in mechanically dissociated rat ventrolateral preoptic neurons. J Neurophysiol 89: 1640 -1648, 2003; 10.1152/jn.00491.2002. The ventrolateral preoptic nucleus (VLPO) is a key nucleus involved in the homeostatic regulation of sleep-wakefulness. Little is known, however, about the cellular mechanisms underlying its role in sleep regulation and how the neurotransmitters, such as GABA and noradrenaline (NA), are involved. In the present study we investigated GABAergic transmission to acutely dissociated VLPO neurons using an enzyme-free, mechanical dissociation procedure in which functional terminals remained adherent and we investigated how this GABAergic transmission was modulated by NA. As previously reported in slices, NA hyperpolarized multipolar VLPO neurons and depolarized bipolar VLPO neurons. NA also inhibited the release of GABA onto multipolar VLPO neurons but had no effect on GABAergic transmission to bipolar neurons. The inhibition of release was mediated by presynaptic ␣ 2 adrenoceptors coupled to N-ethylmaleimide (NEM)-sensitive G-proteins which appeared to act via inhibition of adenylate cyclase and subsequent decreases in protein kinase A activity. The inhibition of GABA release did not, however, involve an inhibition of external Ca 2ϩ influx. The results indicate that all VLPO neurons contain GABAergic inputs and that the different morphological subgroups of VLPO neurons are correlated not only to different postsynaptic responses to NA but also to different presynaptic NA responses. Furthermore our results demonstrate an additional mechanism by which NA can modulate the excitability of multipolar VLPO neurons which may have important implications for its role in regulating sleep/wakefulness.

Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia

“…The loci exhibiting the ADC increase with isoflurane were more extended than with medetomidine. This difference is consistent with the known enhancement by isoflurane of gamma-aminobutyric acid (GABA)ergic inhibitory systems on many brain areas [31], while medetomidine, which is an α2 adrenergic agonist, enhances neural inhibitory systems [32] through norepinephrine and GABA at selective brain regions [33]. The thalamic area is involved in the wakefulness—sleep cycle [34], and a core of those regions (CM, pHT, vmHT, vlPO, DR, and PAG) corresponds to a network known to be associated with wakefulness—sleep conditions [15,35].…”

Propofol Facilitates Glutamatergic Transmission to Neurons of the Ventrolateral Preoptic Nucleus

“…Most of the experiments were done on mechanically dissociated neurons (Fig. 1A1), which combine several advantages: good space clamp, preservation of functioning synaptic terminals, including some that release glutamate, as well as better control of the surrounding solution29,30,34,35. The traces in Fig.…”

Direct Activation of Sleep-Promoting VLPO Neurons by Volatile Anesthetics Contributes to Anesthetic Hypnosis

“…Importantly, despite our best attempts it is possible that an accruing sleep debt 6-days following targeted nanoinjection of galanin-saporin may have minimized a potentially larger magnitude shift in anesthetic resistance that could have resulted from a true acute pharmacologic or genetic inactivation of VLPO. Furthermore, the non-sleep-active NA(+) neurons are also galaninergic [40] and were thus also susceptible to the galanin-saprorin lesion; we would predict that lesioning solely the NA(-) VLPO neurons would produce a larger effect. Based upon preserved temperature and body weight regulation in our lesioned mice, our small volume nanoinjections did not spread to the nearby adjacent median preoptic area, which participates in thermoregulation [41] nor the ventromedial hypothalamus, which contributes to maintenance of body weight [42].…”