Download seminario - Instituto Cajal

SEMINARIO
5 de diciembre de 2014, 12:30
Instituto Cajal. CSIC
Avda. Dr. Arce, 37. Madrid
Prof. Miguel Garzón
Depto. Anatomía, Histología y Neurociencia
Facultad de Medicina
Universidad Autonoma de Madrid
TITLE: Interactions between hypocretinergic perifornical neurons and pontine
tegmentum subdivisions in sleep-wakefulness states regulation and narcoleptic
signs advent
Hypocretin (Hcrt) neurons within the perifornical area (PeF) project to pontine tegmentum areas involved in sleep-wake
control. We report the effects on sleep-wakefulness produced by microinjections of Hcrt delivered in the dorsal (dRPO)
or ventral (vRPO) divisions of the oral pontine tegmentum of free-moving cats with electrodes for chronic sleep
recordings. Hcrt in dRPO increased wakefulness and decreased both NREM and REM sleep. In contrast, Hcrt in vRPO
suppressed REM sleep as the only significant effect on sleep. To determine the cellular mechanisms underlying such
effects in dRPO and vRPO, we examined in urethane-anesthetized rats the effects of PeF stimulation and local Hcrt
application on the electrophysiological activity of dRPO/vRPO neurons. Electrical stimulation of the PeF elicited
orthodromic responses in characterized dRPO and vRPO neurons. Accordingly, anatomical studies showed
retrogradely-labeled neurons from both tegmental areas within the PeF, some of which contained Hcrt, and positive Hcrt
synapses on dRPO and vRPO neurons. Hcrt-1 application in dRPO provoked an increase in dRPO neurons activity that
was blocked with Hcrt-1R antagonists. Iontophoretic application of Hcrt-1 in the vRPO induced an inhibition, which was
blocked by previous iontophoretic application of bicuculline, indicating that inhibitory action of hypocretin-1 may be due
to GABAA receptors activation. Our data also revealed that the dRPO and vRPO neurons exerted a feedback control on
neuronal activity of PeF area. Thus, electrical stimulation of dRPO facilitated firing activity of PeF neurons by activation
of catecholaminergic receptors while vRPO stimulation inhibited PeF neurons by activation of GABAergic receptors.In
conclusion, Hcrt neurons of the PeF area seem to be an important organizer of the wakefulness and sleep stages in
order to maintain a normal succession of stages during the sleep-wakefulness cycle. We will discuss how our data may
explain both hypersomnia and cataplexy emergence in narcoleptics as a consequence of truncated Hcrt signaling in
dRPO and vRPO, respectively.
RECENT PUBLICATIONS
-Cid-Pellitero E. and M. Garzón.
Medial prefrontal cortex receives input from dorsal raphe nucleus neurons targeted by Hypocretin1/OrexinAcontaining axons. Neuroscience 172:30-43. 2011.
-Cid-Pellitero E. and M. Garzón.
Hypocretin1/OrexinA-containing axons innervate locus coeruleus neurons that project to the Rat medial prefrontal
cortex. Implication in the sleep-wakefulness cycle and cortical activation.Synapse 65:843-857. 2011.
-Cid-Pellitero E. and M. Garzón.
Hypocretin1/OrexinA Axon Targeting of Laterodorsal Tegmental Nucleus Neurons Projecting to the Rat Medial
Prefrontal Cortex. Cereb Cortex 21:2762-2773. 2011.
-De Andrés I., M. Garzón and F. Reinoso-Suárez.
Functional Anatomy of Non-REM Sleep. Front Neurol 2:70. 2011.
-Del Cid-Pellitero E. and M. Garzón.
Hypocretin1/orexinA-immunoreactive axons form few synaptic contacts on rat ventral tegmental area
neurons that project to the medial prefrontal cortex. BMC Neurosci 15:105. 2014.