Loss of Snord116 impacts lateral hypothalamus, sleep, and food-related behaviors.

Imprinted genes are highly expressed in the hypothalamus; however, whether specific imprinted genes affect hypothalamic neuromodulators and their functions is unknown. It has been suggested that Prader-Willi syndrome (PWS), a neurodevelopmental disorder caused by lack of paternal expression at chromosome 15q11-q13, is characterized by hypothalamic insufficiency. Here, we investigate the role of the paternally expressed Snord116 gene within the context of sleep and metabolic abnormalities of PWS, and we report a significant role of this imprinted gene in the function and organization of the 2 main neuromodulatory systems of the lateral hypothalamus (LH) - namely, the orexin (OX) and melanin concentrating hormone (MCH) - systems. We observed that the dynamics between neuronal discharge in the LH and the sleep-wake states of mice with paternal deletion of Snord116 (PWScrm+/p-) are compromised. This abnormal state-dependent neuronal activity is paralleled by a significant reduction in OX neurons in the LH of mutant mice. Therefore, we propose that an imbalance between OX- and MCH-expressing neurons in the LH of mutant mice reflects a series of deficits manifested in the PWS, such as dysregulation of rapid eye movement (REM) sleep, food intake, and temperature control.

Neural control of fasting-induced torpor in mice.

Torpor is a peculiar mammalian behaviour, characterized by the active reduction of metabolic rate, followed by a drop in body temperature. To enter torpor, the activation of all thermogenic organs that could potentially defend body temperature must be prevented. Most of these organs, such as the brown adipose tissue, are controlled by the key thermoregulatory region of the Raphe Pallidus (RPa). Currently, it is not known which brain areas mediate the entrance into torpor. To identify these areas, the expression of the early gene c-Fos at torpor onset was assessed in different brain regions in mice injected with a retrograde tracer (Cholera Toxin subunit b, CTb) into the RPa region. The results show a network of hypothalamic neurons that are specifically activated at torpor onset and a direct torpor-specific projection from the Dorsomedial Hypothalamus to the RPa that could putatively mediate the suppression of thermogenesis during torpor.

Effects of acoustic stimulation on cardiovascular regulation during sleep.

The interaction of wake-sleep states and acoustic stimulation on cardiovascular regulation was studied on rats implanted with electroencephalogram and electromyogram electrodes and an arterial catheter. Mild acoustic stimuli (1000 Hz, 90 dB, 50-ms beeps) were administered during Wakefulness (W), non-rapid eye movement (NREM) sleep and REM sleep and the changes induced in heart period (HP, ms) and mean arterial pressure (MAP, mmHg) were analyzed. Two 30-s sequences of beat-to-beat HP and MAP values were considered before (I) and after (II) acoustic stimulation, respectively. By the effect of stimulation, state-dependent stimulus-locked HP and MAP oscillations were observed, HP oscillations being grossly parallel to the MAP ones but delayed with respect to MAP in the ascending part only; HP and MAP spontaneous fluctuations (HP and MAP variability) increased in NREM and REM sleep (but not in W); HP vs MAP correlation coefficient increased in an algebraic sense. These results show that 1) acoustic stimulation primarily affects the peripheral resistance, and secondarily, through the baroreceptor reflex, HP, thereby increasing the impact of peripheral versus centrally driven autonomic influences on the heart; 2) in NREM sleep, heart excitability is higher than requested by the baroreflex function; 3) cardiac variability is increased by acoustic stimulation during sleep (but not in W); this, in addition to the effects of point 2, may favor cardiac arrhythmias in NREM sleep. Thus, mild acoustic stimuli not perturbing cardiovascular regulation during W may create a specific risk factor during sleep in pathophysiologic conditions.